Information on EC 1.6.5.3 - NADH:ubiquinone reductase (H+-translocating)

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Archaea, Bacteria, Eukaryota

EC NUMBER
COMMENTARY
1.6.5.3
-
RECOMMENDED NAME
GeneOntology No.
NADH:ubiquinone reductase (H+-translocating)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
NADH + ubiquinone + 6 H+[side 1] = NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
ping-pong mechanism
-
NADH + ubiquinone + 6 H+[side 1] = NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
ping-pong mechanism
-
NADH + ubiquinone + 6 H+[side 1] = NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
reaction mechanism, overview
-
NADH + ubiquinone + 6 H+[side 1] = NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
tri-bi enzyme mechanism combined with a simple model of the conformational changes associated with proton transport, hybrid ping-pong rapid-equilibrium random bi-bi catalytic mechanism, kinetic mechanism and general kinetic model for conformational change in a tri-bi enzyme mechanism, overview
-
NADH + ubiquinone + 6 H+[side 1] = NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
redox reaction
-
the enzyme oxidizes NADH, produced predominantly by the tricarboxylic acid cycle in the mitochondrial matrix, and reduces ubiquinone in the inner mitochondrial membrane
redox reaction
-
no indication for primary or secondary Na+ translocation
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
aerobic respiration (alternative oxidase pathway)
-
aerobic respiration (cytochrome c)
-
Fe(II) oxidation
-
Metabolic pathways
-
NAD/NADH phosphorylation and dephosphorylation
-
NADH to cytochrome bd oxidase electron transfer
-
NADH to cytochrome bo oxidase electron transfer
-
Oxidative phosphorylation
-
SYSTEMATIC NAME
IUBMB Comments
NADH:ubiquinone oxidoreductase
A flavoprotein (FMN) containing iron-sulfur clusters. The complex is present in mitochondria and aerobic bacteria. Breakdown of the complex can release EC 1.6.99.3, NADH dehydrogenase. In photosynthetic bacteria, reversed electron transport through this enzyme can reduce NAD+ to NADH.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
13 kDa differentiation-associated protein
-
-
-
-
alternative complex I
-
-
alternative NADH oxidoreductase
-
-
alternative NADH: ubiquinone oxidoreductase
-
-
alternative NADH:ubiquinone oxidoreductase
-
-
alternative NADH:ubiquinone oxidoreductase
Caenorhabditis elegans N2
-
-
-
artificial mediator accepting pyridine nucleotide oxidoreductase
-
-
CDA016
-
-
-
-
Cell adhesion protein SQM1
-
-
-
-
Cell death-regulatory protein GRIM-19
-
-
-
-
CGI-39
-
-
-
-
CI-11KD
-
-
-
-
CI-12KD
-
-
-
-
CI-14.8KD
-
-
-
-
CI-14KD
-
-
-
-
CI-15 kDa
-
-
-
-
CI-16KD
-
-
-
-
CI-17.3KD
-
-
-
-
CI-17.8KD
-
-
-
-
CI-18 kDa
-
-
-
-
CI-18Kd
-
-
-
-
CI-19.3KD
-
-
-
-
CI-19KD
-
-
-
-
CI-20KD
-
-
-
-
CI-21KD
-
-
-
-
CI-22.5Kd
-
-
-
-
CI-23KD
-
-
-
-
CI-27KD
-
-
-
-
CI-28.5KD
-
-
-
-
CI-29.9KD
-
-
-
-
CI-29KD
-
-
-
-
CI-30KD
-
-
-
-
CI-31KD
-
-
-
-
CI-38.5KD
-
-
-
-
CI-39KD
-
-
-
-
CI-40KD
-
-
-
-
CI-42.5KD
-
-
-
-
CI-42KD
-
-
-
-
CI-49KD
-
-
-
-
CI-51KD
-
-
-
-
CI-75KD
-
-
-
-
CI-78KD
-
-
-
-
CI-9.5
-
-
-
-
CI-9KD
-
-
-
-
CI-AGGG
-
-
-
-
CI-AQDQ
-
-
-
-
CI-ASHI
-
-
-
-
CI-B12
-
-
-
-
CI-B14
-
-
-
-
CI-B14.5a
-
-
-
-
CI-B14.5b
-
-
-
-
CI-B15
-
-
-
-
CI-B16.6
-
-
-
-
CI-B17
-
-
-
-
CI-B17.2
-
-
-
-
CI-B18
-
-
-
-
CI-B22
-
-
-
-
CI-B8
-
-
-
-
CI-B9
-
-
-
-
CI-KFYI
-
-
-
-
CI-MLRQ
-
-
-
-
CI-MNLL
-
-
-
-
CI-MWFE
-
-
-
-
CI-PDSW
-
-
-
-
CI-PGIV
-
-
-
-
CI-SGDH
-
-
-
-
CIB17.2
-
-
-
-
coenzyme Q reductase
-
-
-
-
complex 1
-
-
complex 1
-
-
complex I
-
-
complex I
-
-
complex I
P17694
-
complex I
Chlamydomonas sp.
-
-
complex I
-
-
complex I
-
in mitochondria
complex I
Escherichia coli ANN023
-
-
-
complex I
Escherichia coli GV102
-
in mitochondria
-
complex I
Escherichia coli MWC215
-
-
-
complex I
-
-
complex I
-
-
complex I
Mus musculus C57/Bl
-
-
-
complex I
-
-
complex I
-
in mitochondria
complex I
-
-
complex I
-
-
complex I
-
-
complex I (electron transport chain)
-
-
-
-
complex I (mitochondrial electron transport)
-
-
-
-
complex I (NADH:Q1 oxidoreductase)
-
-
-
-
complex I dehydrogenase
-
-
-
-
Complex I-11KD
-
-
-
-
Complex I-12KD
-
-
-
-
Complex I-14.8KD
-
-
-
-
Complex I-14KD
-
-
-
-
Complex I-15 kDa
-
-
-
-
Complex I-16KD
-
-
-
-
Complex I-17.3KD
-
-
-
-
Complex I-17.8KD
-
-
-
-
Complex I-18 kDa
-
-
-
-
Complex I-18Kd
-
-
-
-
Complex I-19.3KD
-
-
-
-
Complex I-19KD
-
-
-
-
Complex I-20KD
-
-
-
-
Complex I-21KD
-
-
-
-
Complex I-22.5Kd
-
-
-
-
Complex I-23KD
-
-
-
-
Complex I-27KD
-
-
-
-
Complex I-28.5KD
-
-
-
-
Complex I-29.9KD
-
-
-
-
Complex I-29KD
-
-
-
-
Complex I-30KD
-
-
-
-
Complex I-38.5KD
-
-
-
-
Complex I-39KD
-
-
-
-
Complex I-40KD
-
-
-
-
Complex I-42.5KD
-
-
-
-
Complex I-42KD
-
-
-
-
Complex I-49KD
-
-
-
-
Complex I-51KD
-
-
-
-
Complex I-75KD
-
-
-
-
Complex I-78KD
-
-
-
-
Complex I-9.5KD
-
-
-
-
Complex I-9KD
-
-
-
-
Complex I-AGGG
-
-
-
-
Complex I-AQDQ
-
-
-
-
Complex I-ASHI
-
-
-
-
Complex I-B12
-
-
-
-
Complex I-B14
-
-
-
-
Complex I-B14.5a
-
-
-
-
Complex I-B14.5b
-
-
-
-
Complex I-B15
-
-
-
-
Complex I-B16.6
-
-
-
-
Complex I-B17
-
-
-
-
Complex I-B17.2
-
-
-
-
Complex I-B18
-
-
-
-
Complex I-B22
-
-
-
-
Complex I-B8
-
-
-
-
Complex I-B9
-
-
-
-
Complex I-KFYI
-
-
-
-
Complex I-MLRQ
-
-
-
-
Complex I-MNLL
-
-
-
-
Complex I-MWFE
-
-
-
-
Complex I-PDSW
-
-
-
-
Complex I-PGIV
-
-
-
-
Complex I-SGDH
-
-
-
-
dihydronicotinamide adenine dinucleotide-coenzyme Q reductase
-
-
-
-
DPNH-coenzyme Q reductase
-
-
-
-
DPNH-ubiquinone reductase
-
-
-
-
electron transfer complex I
-
-
-
-
energy-converting NADPH:ubiquinone oxidoreductase
-
-
external alternative NAD(P)H dehydrogenase
-
-
Gene associated with retinoic-interferon-induced mortality 19 protein
-
-
-
-
GGHPW
-
-
-
-
GRIM-19
-
-
-
-
Hypothetical protein Walter
-
-
-
-
Internal NADH dehydrogenase
-
-
-
-
Internal NADH dehydrogenase
-
-
mitochondrial complex I
Q9LK88
-
mitochondrial complex I
-
-
mitochondrial electron transport complex 1
-
-
-
-
mitochondrial electron transport complex I
-
-
-
-
mitochondrial NADH dehydrogenase
-
-
mitochondrial NADH dehydrogenase complex
Q9LK88
-
mitochondrial NADH:ubiquinone oxidoreductase
-
-
mitochondrial proton-pumping NADH-ubiquinone oxidoreductase
P17694
-
NADH coenzyme Q dehydrogenase
-
-
NADH coenzyme Q1 reductase
-
-
-
-
NADH CoQ reductase
-
-
NADH dehydrogenase
-
-
NADH dehydrogenase
-
-
NADH dehydrogenase
-
-
NADH dehydrogenase 1
-
-
NADH dehydrogenase 1 alpha subcomplex 5
-
NDUFA5
NADH dehydrogenase subunit 5
-
-
NADH-coenzyme Q oxidoreductase
-
-
-
-
NADH-coenzyme Q reductase
-
-
-
-
NADH-CoQ oxidoreductase
-
-
-
-
NADH-CoQ oxidoreductase
-
-
NADH-CoQ oxidoreductase
-
-
NADH-CoQ reductase
-
-
-
-
NADH-CoQ1 reductase
-
-
NADH-ferricyanide reductase
-
-
-
-
NADH-Q1 oxidoreductase
-
-
NADH-Q6 oxidoreductase
-
-
-
-
NADH-quinone (NADH-ferricyanide) reductase
-
-
NADH-quinone oxidoreductase
-
-
NADH-quinone oxidoreductase
-
-
NADH-quinone oxidoreductase
-
-
NADH-quinone oxidoreductase
Thermus thermophilus HB-8
-
-
-
NADH-quinone reductase
-
-
-
-
NADH-quinone reductase
-
-
NADH-ubiquinone oxidoreductase
-
-
-
-
NADH-ubiquinone oxidoreductase
-
-
NADH-ubiquinone oxidoreductase
P17694
-
NADH-ubiquinone oxidoreductase
-
-
NADH-ubiquinone oxidoreductase
-
-
NADH-ubiquinone oxidoreductase
-
-
NADH-ubiquinone oxidoreductase
-
-
NADH-ubiquinone oxidoreductase
-
-
NADH-ubiquinone oxidoreductase
-
-
NADH-ubiquinone oxidoreductase
Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera
-
-
NADH-ubiquinone oxidoreductase (complex I)
-
-
NADH-ubiquinone reductase
-
-
-
-
NADH-ubiquinone reductase
-
-
NADH-ubiquinone-1 reductase
-
-
-
-
NADH: n-decylubiquinone oxidoreductase
-
-
NADH: ubiquinone oxidoreductase
-
-
NADH: ubiquinone reductase
-
-
NADH:caldariella quinone oxidoreductase
-
-
NADH:coenzyme Q oxidoreductase
-
-
NADH:CoQ1 oxidoreductase
-
-
NADH:cytochrome c reductase
-
-
NADH:DBQ oxidoreductase
-
-
NADH:external quinone reductase
-
-
NADH:HAR (III) reductase
-
-
NADH:Q oxidoreductase
-
-
-
-
NADH:quinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
Q9LK88
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
Chlamydomonas sp.
-
-
NADH:ubiquinone oxidoreductase
Escherichia coli ANN023, Escherichia coli BW25113, Escherichia coli MWC215
-
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase
-
-
NADH:ubiquinone oxidoreductase complex
-
-
-
-
NADH:ubiquinone-1 oxidoreductase
-
-
NADHubiquinone Q1 oxidoreductase
-
-
NCCR
-
-
ND1
Escherichia coli GV102
-
-
-
Ndh complex
-
-
NDH-1
-
proton-pumping NADH-ubiquinone oxidoreductase
NDH-1
-
in bacteria
NDH-1
Escherichia coli GV102
-
in bacteria
-
NDH-1
Escherichia coli MWC215
-
-
-
NDH-1
-
the NuoG subunit of the type I NADH dehydrogenase
NDH-1
Mycobacterium tuberculosis H37RV (ATCC 25618)
-
the NuoG subunit of the type I NADH dehydrogenase
-
NDH-1
-
in bacteria
NDH-1
-
prokaryotic complex I homolog
NDH-1
Thermus thermophilus HB-8
-
-
-
NDH-2
-
non-proton-pumping NADH-ubiquinone oxidoreductase
NDH-2
-
non-proton-pumping NADH-ubiquinone oxidoreductase
Ndh/NdhAtype II NADH:(mena)quinone oxidoreductase
-
-
Ndi1p
Caenorhabditis elegans N2
-
-
-
nicotinamide adenine dinucleotide-ubiquinone oxidoreductase
-
-
PAI
Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera
-
-
Protein P1
-
-
-
-
proton-pumping NADH-ubiquinone oxidoreductase
-
-
proton-pumping NADH-ubiquinone oxidoreductase
Escherichia coli GV102
-
-
-
proton-pumping NADH-ubiquinone oxidoreductase
-
-
proton-pumping NADH:ubiquinone oxidoreductase
-
-
proton-pumping NADH:ubiquinone oxidoreductase
-
-
proton-translocating NADH-quinone oxidoreductase
-
-
proton-translocating NADH-quinone oxidoreductase
Thermus thermophilus HB-8
-
-
-
proton-translocating NADH: ubiquinone oxidoreductase
-
-
proton-translocating NADH:ubiquinone oxidoreductase
-
-
reduced nicotinamide adenine dinucleotide-coenzyme Q reductase
-
-
-
-
reductase, ubiquinone
-
-
-
-
respiratory chain complex I
-
-
respiratory chain complex I
-
-
respiratory complex I
-
-
respiratory complex I
-
-
respiratory complex I
-
-
-
respiratory complex I
-
-
respiratory complex I
-
-
type 2 NADH:quinone oxidoreductase
-
-
type I dehydrogenase
-
-
-
-
type I NADH dehydrogenase
-
-
type I NADH dehydrogenase
Mycobacterium tuberculosis H37RV (ATCC 25618)
-
-
-
type I NADH dehydrogenase
-
-
type II NADH dehydrogenase
-
-
type II NADH dehydrogenase
-
-
type II NADH:dehydrogenase
-
-
type II NADH:quinone oxidoreductase
-
-
type-2 NADH:quinone oxidoreductase
-
-
type-II NADH dehydrogenase
-
-
type-II NADH dehydrogenase TgNDH2-I
-
-
type-II NADH-menaquinone oxidoreductase
-
-
ubiquinone reductase
-
-
-
-
Ubiquinone-binding protein
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9028-04-0
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain DSM 3772
-
-
Manually annotated by BRENDA team
genes mrpA or mrpD
-
-
Manually annotated by BRENDA team
NDH-1
-
-
Manually annotated by BRENDA team
rotenone-sensitive enzyme complex
-
-
Manually annotated by BRENDA team
Caenorhabditis elegans N2
-
-
-
Manually annotated by BRENDA team
Chlamydomonas sp.
-
-
-
Manually annotated by BRENDA team
var. melopepo, zucchini
-
-
Manually annotated by BRENDA team
Bl21 strain
-
-
Manually annotated by BRENDA team
enzyme form NDH-1
-
-
Manually annotated by BRENDA team
gene nuoA encoding a membrane-spanning subunit of complex I
-
-
Manually annotated by BRENDA team
mutant derivative of strain BW25113 from which the nuo operon is deleted by genomic replacement
-
-
Manually annotated by BRENDA team
NDH-1 and NDH-2
-
-
Manually annotated by BRENDA team
strain ANN023
-
-
Manually annotated by BRENDA team
strain BL21
-
-
Manually annotated by BRENDA team
strain GV102
-
-
Manually annotated by BRENDA team
strain MWC215
-
-
Manually annotated by BRENDA team
wild-type and cells defective for NADH dehydrogenase I
-
-
Manually annotated by BRENDA team
Escherichia coli ANN023
strain ANN023
-
-
Manually annotated by BRENDA team
mutant derivative of strain BW25113 from which the nuo operon is deleted by genomic replacement
-
-
Manually annotated by BRENDA team
Escherichia coli GR19N
GR19N
-
-
Manually annotated by BRENDA team
Escherichia coli GV102
strain GV102
-
-
Manually annotated by BRENDA team
Escherichia coli MWC215
strain MWC215
-
-
Manually annotated by BRENDA team
Tibet chicken
-
-
Manually annotated by BRENDA team
patients with Parkinson's disease from an Indian population
-
-
Manually annotated by BRENDA team
C57/Bl mice
-
-
Manually annotated by BRENDA team
male C57BL/6 mice
-
-
Manually annotated by BRENDA team
Mus musculus C57/Bl
C57/Bl mice
-
-
Manually annotated by BRENDA team
Mycobacterium tuberculosis H37RV (ATCC 25618)
-
-
-
Manually annotated by BRENDA team
rotenone-sensitive enzyme
-
-
Manually annotated by BRENDA team
cultivar Samsun
-
-
Manually annotated by BRENDA team
5-7 days old Wistar rats
-
-
Manually annotated by BRENDA team
7-day-old Sprague-Dawley rat
-
-
Manually annotated by BRENDA team
female Wistar rats
-
-
Manually annotated by BRENDA team
immature 12-day-old male Wistar albino rats
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
SpragueDawley rats
-
-
Manually annotated by BRENDA team
Wistar rats
-
-
Manually annotated by BRENDA team
rotenone-insensitive enzyme
-
-
Manually annotated by BRENDA team
NDH-1 and NDH-2
-
-
Manually annotated by BRENDA team
Thermus thermophilus HB-8
HB-8
-
-
Manually annotated by BRENDA team
Vitis vinifera x Vitis riparia
-
-
-
Manually annotated by BRENDA team
Vitis vinifera x Vitis vinifera
-
-
-
Manually annotated by BRENDA team
var. alkalitolerance
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
-
the complex I subunits NuoL, NuoM and NuoN are homologous to two proteins, MrpA and MrpD, from one particular class of Na+/H+ antiporters. In many bacteria MrpA and MrpD are encoded by an operon comprising 6-7 conserved genes
evolution
-
complex I has been subject to a phenomenal increase in size that predates the diversification of extant eukaryotes, followed by very few lineage-specific additions/losses of subunits
evolution
-
bacterial Complex I is about half the size of the mitochondrial enzyme and is composed of only 13, in Escherichia coli, subunits representing a minimum functional version of the mitochondrial enzyme and performing the same function of coupling redox reaction to proton translocation. Prokaryotic Complex I is much more fragile than the eukaryotic mitochondrial enzyme
evolution
-
bacterial Complex I is about half the size of the mitochondrial enzyme and is composed of only 13, in Escherichia coli, subunits representing a minimum functional version of the mitochondrial enzyme of eukaryotes and performing the same function of coupling redox reaction to proton translocation. Prokaryotic Complex I is much more fragile than the eukaryotic mitochondrial enzyme
malfunction
-
electron transfer and proton translocation activity of complex I variants lacking either NuoL or parts of the C-terminal domain, overview
malfunction
-
deletion of either mrpA or mrpD from the Bacillus subtilis chromosome resulted in a Na+ and pH sensitive growth phenotype. NuoL can rescue Bacillus subtilis DELTAmrpA, but improved the growth of Bacillus subtilis DELTAmrpD only slightly. NuoN can restore the wild type properties of Bacillus subtilis DELTAmrpD, but has no effect on the ?mrpA strain. Expression of NuoM does not result in any growth improvement under these conditions. This reveals that the complex I subunits NuoL, NuoM and NuoN also demonstrate functional specializations
malfunction
Chlamydomonas sp.
-
when present in the homoplasmic state in the alga, the mutation does not prevent assembly of the whole complex I, the NADH dehydrogenase activity of the peripheral arm of the complex is mildly affected. The NADH:duroquinone oxidoreductase activity is strongly reduced, suggesting that the substitution could affect binding of ubiquinone to the membrane domain. The membrane potential is not affected in mutant mitochondria. The in vitro defects correlate with a decrease in dark respiration and growth rate in vivo, phenotype, overview
malfunction
-
defects in complex I are the most frequent cause of human respiratory disorders. Substitution L158P does not lead to any respiratory enzyme defects when present in the heteroplasmic state in a patient with chronic progressive external ophthalmoplegia
physiological function
Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera
-
involved in aromatic amino acid metabolism
physiological function
-
the NuoG subunit of the type I NADH dehydrogenase, NDH-1, is important in Mycobacterium tuberculosis-mediated inhibition of host macrophage apoptosis, the NDH-1 complex is important for NOX2 neutralization in host macrophages
physiological function
-
NDE2 is the main external dehydrogenase responsible for the oxidation of cytosolic NADH and NADPH under physiological conditions
physiological function
-
Ndi1p functionally interacts with the nematode respiratory chain and contributes to the formation of the mitochondrial membrane potential in vivo. Ndi1p expression results in significantly improved reproductive success, better survival under conditions of oxidative stress, fewer signs of premature aging, increased respiration rates and a complete restoration of the in vivo mitochondrial membrane potential in Caenorhabditis elegans nuo-1 mutants. However, Ndi1p is not able to fully replace complex I and cannot support larval development when complex I is missing
physiological function
-
respiratory complex I couples the transfer of electrons from NADH to ubiquinone with a translocation of protons across the membrane
physiological function
-
NADH:ubiquinone oxidoreductase (complex I) is a complicated respiratory enzyme that conserves the energy from NADH oxidation, coupled to ubiquinone reduction, as a proton motive force across the mitochondrial inner membrane. During catalysis, NADH oxidation by a flavin mononucleotide is followed by electron transfer to a chain of iron-sulfur clusters. Alternatively, the flavin may be reoxidized by hydrophilic electron acceptors, by artificial electron acceptors in kinetic studies, or by oxygen and redox-cycling molecules to produce reactive oxygen species
physiological function
-
MrpA transports Na+ whereas MrpD transports H+ in opposite directions, resulting in antiporter activity, besides one Na+ channel, NuoL, and two H+ channels, NuoM and NuoN, are present.
physiological function
-
complex I is one of the respiratory complexes that generate the proton-motive force required for the synthesis of ATP in mitochondria. The electron transfer from NADH to ubiquinone through protein-bound prosthetic groups, which is coupled to the translocation of protons across the inner mitochondrial membrane
physiological function
-
the flavin mononucleotide in complex I catalyzes NADH oxidation, O2 reduction to superoxide, and the reduction of several artificial electron acceptors
physiological function
-
Complex I catalyzes two-electron NADH oxidation and ubiquinone reduction coupled to the transmembrane translocation of 3 or 4 H+ from negatively charged side (N-side, cytoplasm or mitochondrial matrix) to positively charged side (P-side, periplasm or mitochondrial intermembrane space) of the membrane per 2 electrons
physiological function
-
Complex I catalyzes two-electron NADH oxidation and ubiquinone reduction coupled to the transmembrane translocation of 3 or 4H+ from negatively charged side (N-side, cytoplasm or mitochondrial matrix) to positively charged side (P-side, periplasm or mitochondrial intermembrane space) of the membrane per 2 electrons
physiological function
-
the respiratory complex I couples the electron transfer from NADH to ubiquinone with a translocation of protons across the membrane
physiological function
-
in mitochondria, complex I (NADH:ubiquinone oxidoreductase) uses the redox potential energy from NADH oxidation by ubiquinone to transport protons across the inner membrane, contributing to the proton-motive force
physiological function
-
NADH:ubiquinone oxidoreductase (complex I) pumps protons across the membrane using downhill redox energy
physiological function
Q9LK88
The enzyme's major function is the transfer of two electrons from NADH (matrix side) to ubiquinone (inner mitochondrial membrane), biochemical function and physiological role of diverse plant specific complex I subunits, overview
physiological function
Caenorhabditis elegans N2
-
Ndi1p functionally interacts with the nematode respiratory chain and contributes to the formation of the mitochondrial membrane potential in vivo. Ndi1p expression results in significantly improved reproductive success, better survival under conditions of oxidative stress, fewer signs of premature aging, increased respiration rates and a complete restoration of the in vivo mitochondrial membrane potential in Caenorhabditis elegans nuo-1 mutants. However, Ndi1p is not able to fully replace complex I and cannot support larval development when complex I is missing
-
physiological function
-
respiratory complex I couples the transfer of electrons from NADH to ubiquinone with a translocation of protons across the membrane
-
physiological function
Mycobacterium tuberculosis H37RV (ATCC 25618)
-
the NuoG subunit of the type I NADH dehydrogenase, NDH-1, is important in Mycobacterium tuberculosis-mediated inhibition of host macrophage apoptosis, the NDH-1 complex is important for NOX2 neutralization in host macrophages
-
malfunction
-
electron transfer and proton translocation activity of complex I variants lacking either NuoL or parts of the C-terminal domain, overview
-
additional information
-
the complex consists of a peripheral arm catalyzing the electron transfer reaction and a membrane arm involved in proton translocation. The energy released by the redox reaction is transmitted to the membrane arm via a conformational change in the horizontal helix. The helix corresponds to the C-terminal part of the most distal subunit NuoL. The C-terminal domain of NuoL is essential for the translocation of 2H+/2e-
additional information
-
mechanism of NADH oxidation by complex I, the adenosine moiety of NADH is crucial for binding, overview
additional information
-
the accessory subunits of eukaryotic complex I bear an allosteric ATP binding site
additional information
-
the accessory subunits of eukaryotic complex I bear an allosteric ATP binding site
additional information
-
NuoA is a small membrane spanning subunit of respiratory chain NADH:quinone oxidoreductase (complex I). Unlike the other complex I core protein subunits, the NuoA protein has no known homologue in other enzyme systems
additional information
-
potential energy profile for the Complex I substrates and cofactors, overview
additional information
-
potential energy profile for the Complex I substrates and cofactors, overview. Redox potentials of mitochondrial respiratory complexes, overview. Two domains, hydrophilic and hydrophobic, constitute Complex I. The hydrophilic domain of Complex I contains noncovalently bound FMN and 8-9 FeS clusters, 8 of which are organized as a continuous eT chain connecting FMN and a UQ binding site. One or two UQ-binding sites are located at the interface between the hydrophilic and membrane Complex I domains or in the membrane domain close to the interface area. The hydrophilic domain is composed of 6 or 7 core subunits and protrudes to cytoplasm or mitochondrial matrix. The substrate binding site is located in the open cleft on the surface of the protein. The conserved residues aligning this solvent-accessible cavity form an unusual Rossmann fold, which provides tight packing of the substrate, ensures the planar condensed system of the nicotinamide and the FMN isoalloxazine rings and therefore determines high affinity to NADH, substrate specificity and high rate of hydride transfer to FMN. Structure-function modeling, different mechanistic models, detailed overview
additional information
-
the deactive state of complex I is formed during hypoxia, when respiratory chain turnover is slowed, and may contribute to determining the outcome of ischemia-reperfusion injury
additional information
-
the complex consists of a peripheral arm catalyzing the electron transfer reaction and a membrane arm involved in proton translocation. The energy released by the redox reaction is transmitted to the membrane arm via a conformational change in the horizontal helix. The helix corresponds to the C-terminal part of the most distal subunit NuoL. The C-terminal domain of NuoL is essential for the translocation of 2H+/2e-
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,3-dimethyl-1,4-naphthoquinone + NADH + H+
2,3-dimethyl-1,4-hydronaphthoquinol + NAD+
show the reaction diagram
-
-
-
-
?
2-methyl-1,4-naphthoquinone + NADH + H+
2-methyl-1,4-naphthoquinol + NAD+
show the reaction diagram
-
specific for NADH, i.e. menadione
-
-
?
amplex red + NADH + O2
resorufin + NAD+ + H2O2
show the reaction diagram
-
the rate of H2O2 formation by complex I strongly depends upon the NAD+/NADH ratio
-
-
?
benzoquinone + NADH + H+
benzohydroquinone + NAD+
show the reaction diagram
-
-
-
-
?
deamino-NADH + dimethoxy-5-methyl-6-decyl-1,4-benzoquinone
deamino-NAD+ + reduced dimethoxy-5-methyl-6-decyl-1,4-benzoquinone
show the reaction diagram
-
-
-
-
?
deamino-NADH + ferricyanide
deamino-NAD+ + ferrocyanide
show the reaction diagram
-
-
-
-
?
deamino-NADH + ferricyanide
deamino-NAD+ + ferrocyanide
show the reaction diagram
Escherichia coli ANN023
-
-
-
-
?
deamino-NADH + ubiquinone
deamino-NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
deamino-nicotinamide-adeninedinucleotide + n-decylubiquinone
? + n-decylubiquinol
show the reaction diagram
-
-
-
-
?
decyl-ubiquinone + NADH
decyl-ubiquinol + NAD+
show the reaction diagram
-
-
-
-
?
decyl-ubiquinone + NADH + H+
decyl-ubiquinol + NAD+
show the reaction diagram
-
-
-
-
?
dihydroethidium + O2
ethidium + H2O2
show the reaction diagram
-
dihydroethidium reduction shows that, upon reducing O2, it produces approximately 20% superoxide and 80% H2O2
-
-
?
ferricyanide + NADH + H+
ferrocyanide + NAD+
show the reaction diagram
-
-
-
-
?
glutamate
?
show the reaction diagram
-
-
-
-
?
malate
?
show the reaction diagram
-
-
-
-
?
NADH + 1,1'-carbamoylmethylviologen
NAD+ + reduced 1,1'-carbamoylmethylviologen
show the reaction diagram
-
-
-
-
r
NADH + 2,3-dimethoxy-5-methyl-6-isoprenyl-1,4-benzoquinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2,3-dimethoxy-5-methyl-6-[(6-methyl-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2,3-dimethoxy-5-methyl-6-[(6-methyl-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2,3-dimethoxy-5-methyl-6-[(6-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2,3-dimethoxy-5-methyl-6-[(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenol indophenol
show the reaction diagram
-
-
-
-
?
NADH + 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenol indophenol
show the reaction diagram
-
-
-
-
?
NADH + 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenol indophenol
show the reaction diagram
-
-
-
-
?
NADH + 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenol indophenol
show the reaction diagram
-
-
-
-
-
NADH + 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenol indophenol
show the reaction diagram
-
-
-
-
?
NADH + 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenol indophenol
show the reaction diagram
-
2,6-dichlorophenol indophenol as electron acceptor
-
-
?
NADH + 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenol indophenol
show the reaction diagram
-
41.7% of the activity with ubiquinone-1
-
-
?
NADH + 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
?
NADH + 2,6-dichlorophenolindophenol
NAD+ + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
?
NADH + 2,6-dichlorophenolindophenol
NAD+ + ?
show the reaction diagram
-
2,6-dichlorophenolindophenol is a poor electron acceptor
-
?
NADH + 2-methyl-1,4-naphthoquinone
NAD+ + 2-methyl-1,4-naphthoquinol
show the reaction diagram
-
-
-
-
?
NADH + 2-methylnaphthoquinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2-methylnaphthoquinone
NAD+ + ?
show the reaction diagram
-
7.6% of the activity with ubiquinone-1
-
-
?
NADH + 2-[(2,6-dimethylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2-[(2-chloro-6-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2-[(2-chloro-6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2-[(6-chloro-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2-[(6-chloro-2-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 2-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 3'-acetyl pyridine adenine dinucleotide
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + 6-decyl-ubiquinone
NAD+ + 6-decyl-ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + anthraquinone-2,6-disulfonate
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + benzoquinone
NAD+ + benzoquinol
show the reaction diagram
-
-
-
-
?
NADH + benzoquinone + H+
NAD+ + benzoquinol
show the reaction diagram
-
-
-
-
?
NADH + caldariellaquinone
NAD+ + caldariellaquinol
show the reaction diagram
-
-
-
-
?
NADH + caldariellaquinone
NAD+ + caldariellaquinol
show the reaction diagram
-
-
-
-
?
NADH + caldariellaquinone
NAD+ + caldariellaquinol
show the reaction diagram
-
-
-
-
?
NADH + coenzyme Q0
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + coenzyme Q1
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + coenzyme Q1 + H+
NAD+ + reduced coenzyme Q1
show the reaction diagram
-
-
-
-
?
NADH + coenzyme Q10
?
show the reaction diagram
-
-
-
-
?
NADH + coenzyme Q10
?
show the reaction diagram
-
-
-
-
?
NADH + coenzyme Q2
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + cytochrome c
NAD+ + reduced cytochrome c
show the reaction diagram
-
-
-
-
?
NADH + cytochrome c
NAD+ + reduced cytochrome c
show the reaction diagram
-
-
-
-
?
NADH + cytochrome c
NAD+ + reduced cytochrome c
show the reaction diagram
-
-
-
-
?
NADH + cytochrome c
NAD+ + reduced cytochrome c
show the reaction diagram
-
12%-16% of the activity with ubiquinone-1
-
-
?
NADH + cytochrome c
NAD+ + reduced cytochrome c
show the reaction diagram
-
8.3% of the activity with ubiquinone-1
-
-
?
NADH + decyl-ubiquinone
NAD+ + decyl-ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + decyl-ubiquinone + H+
NAD+ + decyl-ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
n-decylubiquinone
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
no activity with the enzymatically active subcomplexes Ilambda, IS, and IlamdaS at similar rates to complex I
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
ordered sequential mechanism in which the order of substrate bindings and product release is: NADH, decylubiquinone, decylubiquinol, NAD+
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
Escherichia coli MWC215
-
-
-
-
?
NADH + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
Escherichia coli GV102
-
-
-
-
?
NADH + decylubiquinone + H+
NAD+ + decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + duroquinone
NAD+ + duroquinol
show the reaction diagram
-
-
-
?
NADH + duroquinone
NAD+ + duroquinol
show the reaction diagram
-
-
-
-
?
NADH + duroquinone
NAD+ + duroquinol
show the reaction diagram
-
64.5% of the activity with ubiquinone-1
-
-
?
NADH + duroquinone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + FAD
NAD+ + FADH2
show the reaction diagram
-
-
-
-
?
NADH + Fe(CN)63-
?
show the reaction diagram
-
-
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
-
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
-
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
-
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
-
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
-
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
-
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
-
-
-
-
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
activity is 27.4fold of the activity with ubiquinone-1
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
232.7% of the activity with ubiquinone-1
-
-
?
NADH + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
Escherichia coli ANN023
-
-
-
-
?
NADH + ferricytochrome c
NAD+ + ferrocytochrome c
show the reaction diagram
-
-
-
-
?
NADH + H+ + 1,4-benzoquinone
NAD+ + 1,4-benzoquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + 1,4-naphthoquinone
NAD+ + 1,4-naphthoquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + 1,4-naphthoquinone
NAD+ + 1,4-naphthoquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + 2,5-dimethyl-1,4-benzoquinone
NAD+ + 2,5-dimethyl-1,4-benzoquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + 2-methyl-1,4-naphthoquinone
NAD+ + 2-methyl-1,4-naphthoquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + 2-methyl-l,4-benzoquinone
NAD+ + 2-methyl-l,4-benzoquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + 4-nitroacetophenone
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + H+ + 4-nitrobenzaldehyde
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + H+ + 4-nitrobenzoic acid
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + H+ + 5,8-dioxy-1,4-naphthoquinone
NAD+ + 5,8-dioxy-1,4-naphthoquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + 5-oxy-1,4-naphthoquinone
NAD+ + 5-oxy-1,4-naphthoquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + 9,10-phenanthrenequinone
NAD+ + 9,10-phenanthrenequinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + adriamycin
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + H+ + coenzyme Q1
NAD+ + reduced coenzyme Q1
show the reaction diagram
-
-
-
-
?
NADH + H+ + coenzyme Q1
NAD+ + reduced coenzyme Q1
show the reaction diagram
-
-
-
-
?
NADH + H+ + coenzyme Q1
NAD+ + reduced coenzyme Q1
show the reaction diagram
-
-
-
-
?
NADH + H+ + coenzyme Q1
NAD+ + reduced coenzyme Q1
show the reaction diagram
-
ordered sequential mechanism in which the order of substrate binding and product release is coenzyme Q1, NADH, NAD+ and reduced coenzyme coenzyme Q1
-
-
?
NADH + H+ + coenzyme Q2
NAD+ + reduced coenzyme Q2
show the reaction diagram
-
-
-
-
?
NADH + H+ + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
decylubiquinone is slightly better than ubiquinone-1 as electron acceptor
-
-
?
NADH + H+ + decylubiquinone
NAD+ + decylubiquinol
show the reaction diagram
-
the enzyme is selective for NADH
-
-
?
NADH + H+ + ferricyanide
NAD+ + ferrocyanide
show the reaction diagram
-
-
-
-
?
NADH + H+ + idebenone
NAD+ + ?
show the reaction diagram
-
studies of ubiquinone reduction by isolated complex I are problematic because the extremely hydrophobic natural substrate, ubiquinone-10, must be substituted with a relatively hydrophilic analogue (such as ubiquinone-1). Hydrophilic ubiquinones are reduced by an additional, non-energy-transducing pathway. Inhibitor-insensitive ubiquinone reduction occurs by a ping-pong type mechanism, catalyzed by the flavin mononucleotide cofactor in the active site for NADH oxidation. Moreover, semiquinones produced at the flavin site initiate redox cycling reactions with molecular oxygen, producing superoxide radicals and hydrogen peroxide. The ubiquinone reactant is regenerated, so the NADH:Q reaction becomes superstoichiometric. Idebenone, an artificial ubiquinone, reacts at the flavin site
-
-
?
NADH + H+ + menadione
NAD+ + menadiol
show the reaction diagram
-
-
-
-
?
NADH + H+ + menaquinone
NAD+ + menaquinol
show the reaction diagram
-
the enzyme plays an essential role in maintaining a reduced ubiquinone-pool during infection (Mycobacterium tuberculosis is the causative agents of tuberculosis). The enzyme is not only essential to parasite survival in vivo but may also contribute to the severity and outcome of disease. Type II NADH:quinone oxidoreductase the membrane-bound respiratory enzyme differs from the canonical NADH:dehydrogenase (complex I), because it is not involved in the vectorial transfer of protons across membranes. Mycobacterium tuberculosis contains a branched respiratory chain terminating in a cytochrome bd (quinol) oxidase and an aa3-type cytochrome c oxidase. Both chains are fed by a menaquinol (MQH2) pool that is generated by four dehydrogenases; one succinate menaquinone oxidoreductase (SQR), one multimeric type I NADH: dehydrogenase (complex I), and two type II NADH: menaquinone oxidoreductases (ndh and ndhA). Transposon insertion knockout strategy reveals that disruption of the ndh gene is lethal
-
-
?
NADH + H+ + nitrobenzene
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + H+ + nitrofurantoin
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + H+ + oxidized dichlorophenolindophenol
NAD+ + reduced dichlorophenolindophenol
show the reaction diagram
-
-
-
-
?
NADH + H+ + tetramethyl-1,4-benzoquinone
NAD+ + tetramethyl-1,4-benzoquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
conserved lysine residues of the membrane subunit NuoM are involved in energy conversion by the proton-pumping NADH:ubiquinone oxidoreductase
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
NADH:ubiquinone oxidoreductase or complex I is a large multisubunit assembly of the mitochondrial inner membrane that channels high-energy electrons from metabolic NADH into the electron transport chain. Its dysfunction is associated with a range of progressive neurological disorders, often characterized by a very early onset and short devastating course. Reduction in cellular complex I activity leads to a depolarization of the mitochondrial membrane potential, resulting in a decreased supply of mitochondrial ATP to the Ca2+-ATPases of the intracellular stores and thus to a reduced Ca2+ content of these stores
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
the energy-converting NADH:ubiquinone oxidoreductase (respiratory complex I), couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Caenorhabditis elegans N2
-
-
-
-
?
NADH + H+ + ubiquinone-0
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone-0
NAD+ + ubiquinol-0
show the reaction diagram
-
prefers ubiquinol-0 as an acceptor substrate, and can also use the artificial electron acceptors, menadione and dichlorophenolindophenol
-
-
?
NADH + H+ + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
P17694
-
-
-
?
NADH + H+ + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
formation of the semiquinone signals during steady state electron transfer from NADH to ubiquinone-1
-
-
?
NADH + H+ + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
studies of ubiquinone reduction by isolated complex I are problematic because the extremely hydrophobic natural substrate, ubiquinone-10, must be substituted with a relatively hydrophilic analogue (such as ubiquinone-1). Hydrophilic ubiquinones are reduced by an additional, non-energy-transducing pathway. Inhibitor-insensitive ubiquinone reduction occurs by a ping-pong type mechanism, catalyzed by the flavin mononucleotide cofactor in the active site for NADH oxidation. Moreover, semiquinones produced at the flavin site initiate redox cycling reactions with molecular oxygen, producing superoxide radicals and hydrogen peroxide. The ubiquinone reactant is regenerated, so the NADH:Q reaction becomes superstoichiometric. Idebenone, an artificial ubiquinone, reacts at the flavin site
-
-
?
NADH + H+ + ubiquinone-10
NAD+ + ubiquinol-10
show the reaction diagram
-
the natural substrate ubiquinone-10 is extremely hydrophobic, studies of ubiquinone reduction by isolated complex I are problematic because the extremely hydrophobic natural substrate, ubiquinone-10, must be substituted with a relatively hydrophilic analogue (such as ubiquinone-1). Hydrophilic ubiquinones are reduced by an additional, non-energy-transducing pathway. Inhibitor-insensitive ubiquinone reduction occurs by a ping-pong type mechanism, catalyzed by the flavin mononucleotide cofactor in the active site for NADH oxidation. Moreover, semiquinones produced at the flavin site initiate redox cycling reactions with molecular oxygen, producing superoxide radicals and hydrogen peroxide. The ubiquinone reactant is regenerated, so the NADH:Q reaction becomes superstoichiometric. Idebenone, an artificial ubiquinone, reacts at the flavin site
-
-
?
NADH + H+ nifuroxim
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + hexaamineruthenium(III) chloride
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + hexaammineruthenium-(III)-chloride
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + hexaammineruthenium-III-chloride
NAD+ + ?
show the reaction diagram
Escherichia coli, Escherichia coli MWC215
-
-
-
-
?
NADH + hexamineruthenium(III)-chloride
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + hexammineruthenium-(III)-chloride
NAD+ + ?
show the reaction diagram
-
-
-
-
?
NADH + menadione
NAD+ + menadiol
show the reaction diagram
-
-
-
-
?
NADH + menadione
NAD+ + menadiol
show the reaction diagram
-
menadione is a poor electron acceptor
-
?
NADH + menadione
NAD+ + reduced menadione
show the reaction diagram
-
-
-
-
?
NADH + menaquinone
NAD+ + menaquinol
show the reaction diagram
-
-
-
-
?
NADH + n-decylubiquinone + H+
NAD+ + n-decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + n-decylubiquinone + H+
NAD+ + n-decylubiquinol
show the reaction diagram
-
-
-
-
?
NADH + naphthoquinone
NAD+ + naphthoquinol
show the reaction diagram
-
-
-
-
?
NADH + O2
NAD+ + superoxide radical
show the reaction diagram
-
-
-
-
?
NADH + O2
NAD+ + superoxide radical
show the reaction diagram
-
-
-
?
NADH + O2
NAD+ + superoxide radical
show the reaction diagram
-
addition of NADH, but not decylubiquinol, leads to superoxide production
-
-
?
NADH + phylloquinone
NAD+ + phylloquinol
show the reaction diagram
-
-
-
-
?
NADH + plastoquinone
NAD+ + plastoquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Escherichia coli MWC215
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Thermus thermophilus HB-8
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Thermus thermophilus HB-8
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Thermus thermophilus HB-8
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Thermus thermophilus HB-8
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Escherichia coli ANN023
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Escherichia coli GR19N
-
-
-
-
?
NADH + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Escherichia coli GV102
-
-
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
-
-
-
-
NADH + ubiquinone
?
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
the enzyme catalyzes the transfer of electrons without translocation of protons across the membrane
-
-
-
NADH + ubiquinone
?
show the reaction diagram
-
NADH-ubiquinone reductase complex I is involved in the respiratory chain
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
vectorial electron translocation is coupled to electron transfer
-
-
-
NADH + ubiquinone
?
show the reaction diagram
-
mutations in NADH:ubiquinone oxidoreductase NADH of Escherichia coli affect growth on mixed amino acids, because the large NADH/NAD+ ratio inhibits enzymes, e.g. citrate synthase and malate dehydrogenase, shared by the tricarboxylic acid cycle and the glyoxylate shunt
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
proton-translocating NADH-ubiquinone oxidoreductase is the largest multiprotein complex of the respiratory chain
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
enzyme is involved in respiratory chain
-
-
?
NADH + ubiquinone
?
show the reaction diagram
Thermus thermophilus HB-8
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
electron transfer path from FMN to ubiquinone through the FeS cluster chain. Upon the oxidation of one NADH molecule 4H+ are translocated across the membrane from N-side (cytoplasm, equivalent to the mitochondrial matrix) to P-side (periplasm, equivalent to the mitochondrial intermembrane space)
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + H+
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-0
NAD+ + ubiquinol-0
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-0
NAD+ + ubiquinol-0
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-0
NAD+ + ubiquinol-0
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1
NAD+ + ubiquinol-1
show the reaction diagram
-
reaction is catalyzed by the enzymatically active subcomplexes Ilambda, IS, and IlamdaS at similar rates to complex I
-
-
?
NADH + ubiquinone-1
NAD+ + reduced ubiquinone-1
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-1 + H+
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-10
NAD+ + ubiquinol-10
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-10
NAD+ + ubiquinol-10
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + reduced ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + reduced ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + reduced ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + reduced ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + reduced ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-2
NAD+ + ubiquinol-2
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-6
NAD+ + ubiquinol-6
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone-6
NAD+ + ubiquinol-6
show the reaction diagram
-
86% of the activity with ubiquinone-1
-
-
?
NADH + ubiquinone-8
NAD+ + ubiquinol-8
show the reaction diagram
Escherichia coli, Escherichia coli MWC215
-
-
-
-
?
NADH + ubiquinone-9
NAD+ + ubiquinol-9
show the reaction diagram
-
-
-
-
-
NADPH + 2-methylnaphthoquinone
NADP+ + ?
show the reaction diagram
-
about 1% of the activity with NADH
-
-
?
NADPH + ferricyanide
NADP+ + ferrocyanide
show the reaction diagram
-
0.13% of the activity with NADH and ferricyanide
-
-
?
NADPH + ferricyanide
NADP+ + ferrocyanide
show the reaction diagram
-
about 1% of the activity with NADH
-
-
?
NADPH + H+ + ubiquinone
NADP+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADPH + H+ + ubiquinone
NADP+ + ubiquinol
show the reaction diagram
-
the enzyme has a lower affinity to NADPH than to NADH
-
-
?
NADPH + H+ + ubiquinone-1
NADP+ + ubiquinol-1
show the reaction diagram
-
at a slow rate
-
-
?
NADPH + ubiquinone + 6 H+[side 1]
NADP+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
NADPH is a poor substrate of the complex
-
-
?
oxidized 2,6-dichlorophenolindophenol + NADH + H+
reduced 2,6-dichlorophenolindophenol + NADP+
show the reaction diagram
-
-
-
-
?
succinate + O2 + NAD+
NADH + ?
show the reaction diagram
-
-
-
-
?
ubiquinone + NADH + H+
ubiquinol + NAD+
show the reaction diagram
-
-
-
-
?
ubiquinone-1 + NADH + H+
ubiquinol-1 + NAD+
show the reaction diagram
-
-
-
-
?
ubiquinone-1 + NADH + H+
ubiquinol-1 + NAD+
show the reaction diagram
-
the protein shows NADH-ubiquinone-1 oxidoreductase activity, NADPH oxidase (EC 1.6.3.1) and NADPH-ubiquinone-1 oxidoreductase (EC 1.6.5.2) activities
-
-
?
malate + pyruvate + O2
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
NADH-NADP transhydrogenation at a very slow rate
-
-
-
additional information
?
-
-
no transhydrogenase activity with NADPH
-
-
-
additional information
?
-
-
no activity with coenzyme Q10
-
-
-
additional information
?
-
-
complex I is a primary electrogenic proton pump and may be capable of secondary sodium antiport. The magnitude of the pH-gradient depends on the sodium concentration
-
-
-
additional information
?
-
-
superoxide production from complex I is large under conditions of reverse electron transport. Production of superoxide by complex I during reverse electron transport is at least 3fold more sensitive to the pH gradient than to the membrane potential
-
-
-
additional information
?
-
-
superoxide production rates by complex I during reverse electron transfer are much greater than during forwards electron transfer. The major site of superoxide production in complex I is the quinpone-binding site, it is most likely a semiquinone
-
-
-
additional information
?
-
-
the enzyme mediates electron transfer to particulate methane monooxygenase
-
-
-
additional information
?
-
-
does not react with NADPH or oxygen
-
-
-
additional information
?
-
-
FMN-dependent NADH-quinone reductase induced by menadione
-
-
-
additional information
?
-
-
NADH:ubiquinone oxidoreductase (EC 1.6.5.3) constitutes the entry point of electrons in the electron transport chain. Mitochondrial NADH:ubiquinone oxidoreductase or complex I (CI) is a frequently affected enzyme in cases of mitochondrial disorders
-
-
-
additional information
?
-
-
complex I also shows NADH oxidase activity
-
-
-
additional information
?
-
-
no activity with coenzyme Q4 and coenzyme QD
-
-
-
additional information
?
-
-
no redox-coupled Na+ transport and no Na+/H+ antiporter function by the enzyme from Yarrowia lipolytica
-
-
-
additional information
?
-
-
no redox-coupled Na+ transport, but the deactive form of complex I, which is formed spontaneously when enzyme turnover is precluded by lack of substrates, is a Na+/H+ antiporter. The antiporter activity is Na+-specific and is abolished upon reactivation by the addition of substrates and by the complex I inhibitor rotenone. It is specific for Na+ over K+
-
-
-
additional information
?
-
-
hexaammineruthenium (III) chloride, i.e. HAR, can act as artificial electron acceptor. The rate of NADH oxidation by the artificial electron acceptor HAR is about 10fold higher than NADH oxidase activity and is insensitive to rotenone and piericidin
-
-
-
additional information
?
-
-
the enzyme shows also rotenone-insensitive NADH:hexaammineruthenium III (HAR) oxidoreductase activity
-
-
-
additional information
?
-
-
the enzyme shows also rotenone-insensitive NADH:hexaammineruthenium III (HAR) oxidoreductase activity. The enzyme NDH-1 catalyzes a number of the NADH:artificial electron acceptor oxidoreductase activities showing particularly high turnover numbers with ferricyanide and hexaammineruthenium(III), kinetic patterns of the steady-state NADH oxidation with these two electron acceptors, overview
-
-
-
additional information
?
-
-
the positively-charged electron acceptors paraquat and hexaammineruthenium(III) react with the nucleotide-bound reduced flavin in complex I, by an unusual ternary mechanism, overview. The mechanism for paraquat reduction defines another mechanism for superoxide production by complex I by redox cycling
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
NADH + H+ + menaquinone
NAD+ + menaquinol
show the reaction diagram
-
the enzyme plays an essential role in maintaining a reduced ubiquinone-pool during infection (Mycobacterium tuberculosis is the causative agents of tuberculosis). The enzyme is not only essential to parasite survival in vivo but may also contribute to the severity and outcome of disease. Type II NADH:quinone oxidoreductase the membrane-bound respiratory enzyme differs from the canonical NADH:dehydrogenase (complex I), because it is not involved in the vectorial transfer of protons across membranes. Mycobacterium tuberculosis contains a branched respiratory chain terminating in a cytochrome bd (quinol) oxidase and an aa3-type cytochrome c oxidase. Both chains are fed by a menaquinol (MQH2) pool that is generated by four dehydrogenases; one succinate menaquinone oxidoreductase (SQR), one multimeric type I NADH: dehydrogenase (complex I), and two type II NADH: menaquinone oxidoreductases (ndh and ndhA). Transposon insertion knockout strategy reveals that disruption of the ndh gene is lethal
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
-
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
conserved lysine residues of the membrane subunit NuoM are involved in energy conversion by the proton-pumping NADH:ubiquinone oxidoreductase
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
NADH:ubiquinone oxidoreductase or complex I is a large multisubunit assembly of the mitochondrial inner membrane that channels high-energy electrons from metabolic NADH into the electron transport chain. Its dysfunction is associated with a range of progressive neurological disorders, often characterized by a very early onset and short devastating course. Reduction in cellular complex I activity leads to a depolarization of the mitochondrial membrane potential, resulting in a decreased supply of mitochondrial ATP to the Ca2+-ATPases of the intracellular stores and thus to a reduced Ca2+ content of these stores
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
-
the energy-converting NADH:ubiquinone oxidoreductase (respiratory complex I), couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane
-
-
?
NADH + H+ + ubiquinone
NAD+ + ubiquinol
show the reaction diagram
Caenorhabditis elegans N2
-
-
-
-
?
NADH + H+ + ubiquinone-10
NAD+ + ubiquinol-10
show the reaction diagram
-
the natural substrate ubiquinone-10 is extremely hydrophobic
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
-
-
-
-
NADH + ubiquinone
?
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
the enzyme catalyzes the transfer of electrons without translocation of protons across the membrane
-
-
-
NADH + ubiquinone
?
show the reaction diagram
-
NADH-ubiquinone reductase complex I is involved in the respiratory chain
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
vectorial electron translocation is coupled to electron transfer
-
-
-
NADH + ubiquinone
?
show the reaction diagram
-
mutations in NADH:ubiquinone oxidoreductase NADH of Escherichia coli affect growth on mixed amino acids, because the large NADH/NAD+ ratio inhibits enzymes, e.g. citrate synthase and malate dehydrogenase, shared by the tricarboxylic acid cycle and the glyoxylate shunt
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
proton-translocating NADH-ubiquinone oxidoreductase is the largest multiprotein complex of the respiratory chain
-
-
?
NADH + ubiquinone
?
show the reaction diagram
-
enzyme is involved in respiratory chain
-
-
?
NADH + ubiquinone
?
show the reaction diagram
Thermus thermophilus HB-8
-
proton-translocating enzyme
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
electron transfer path from FMN to ubiquinone through the FeS cluster chain. Upon the oxidation of one NADH molecule 4H+ are translocated across the membrane from N-side (cytoplasm, equivalent to the mitochondrial matrix) to P-side (periplasm, equivalent to the mitochondrial intermembrane space)
-
-
?
NADH + ubiquinone + 6 H+[side 1]
NAD+ + ubiquinol + 7 H+[side 2]
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
complex I is a primary electrogenic proton pump and may be capable of secondary sodium antiport. The magnitude of the pH-gradient depends on the sodium concentration
-
-
-
additional information
?
-
-
superoxide production from complex I is large under conditions of reverse electron transport. Production of superoxide by complex I during reverse electron transport is at least 3fold more sensitive to the pH gradient than to the membrane potential
-
-
-
additional information
?
-
-
superoxide production rates by complex I during reverse electron transfer are much greater than during forwards electron transfer. The major site of superoxide production in complex I is the quinpone-binding site, it is most likely a semiquinone
-
-
-
additional information
?
-
-
the enzyme mediates electron transfer to particulate methane monooxygenase
-
-
-
additional information
?
-
-
FMN-dependent NADH-quinone reductase induced by menadione
-
-
-
additional information
?
-
-
NADH:ubiquinone oxidoreductase (EC 1.6.5.3) constitutes the entry point of electrons in the electron transport chain. Mitochondrial NADH:ubiquinone oxidoreductase or complex I (CI) is a frequently affected enzyme in cases of mitochondrial disorders
-
-
-
additional information
?
-
-
no redox-coupled Na+ transport and no Na+/H+ antiporter function by the enzyme from Yarrowia lipolytica
-
-
-
additional information
?
-
-
no redox-coupled Na+ transport, but the deactive form of complex I, which is formed spontaneously when enzyme turnover is precluded by lack of substrates, is a Na+/H+ antiporter. The antiporter activity is Na+-specific and is abolished upon reactivation by the addition of substrates and by the complex I inhibitor rotenone. It is specific for Na+ over K+
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
deamino-NADH
-
-
FAD
-
contains a single molecule of FAD per subunit
FAD
-
enzyme contains FAD
FAD
-
enzyme contains 13.47 nM of FMN per mg of enzyme
FAD
-
2.97 nmol per mg of enzyme
FAD
-
requires FMN or FAD as cofactor, FMN is more effective. Half-maximum activity is obtained with 0.00054 mM FMN or 0.0165 mM FAD
FAD
-
noncovalently bound
flavin
-
enzyme contains 1.4 mol flavin per mol of enzyme
FMN
-
contains 1 FMN per 650000 Da enzyme
FMN
-
enzyme contains noncovalently bound FMN
FMN
-
contains 0.5 mol of FMN per mol of isolated enzyme
FMN
-
enzyme contains one noncovalently bound FMN
FMN
-
the enzyme complex contains one molecule of FMN
FMN
-
enzyme contains FMN
FMN
-
enzyme contains noncovalently bound FMN
FMN
-
enzyme requires FMN or FAD as cofactor, FMN is 30times more effective. Half-maximum activity is obtained with 0.00054 mM FMN or 0.0165 mM FAD
FMN
-
covalently attached. The average reduction potential of the FMN is + 160 mV, at 25C and pH 6.5
FMN
-
O2 reacts with the fully reduced flavin mononucleotide
FMN
-
contains FMN
FMN
-
contains non-covalently bound flavin mononucleotide. Hydrophilic ubiquinones are reduced by an additional, non-energy-transducing pathway. Inhibitor-insensitive ubiquinone reduction occurs by a ping-pong type mechanism, catalyzed by the flavin mononucleotide cofactor in the active site for NADH oxidation
FMN
-
0.94-0.1 of FMN//1 mol of complex I
iron-sulfur centre
-
the enzyme contains 8-9 iron-sulfur clusters
NADH
-
no activity with NADPH
NADH
-
no activity with NADPH
NADH
-
no activity with NADPH
NADH
-
no activity with NADPH
NADH
-
binding to the enzyme results in a conformational change, in the coenzyme Q binding site, which enables the site to accept coenzyme Q with a side chain significantly larger than one isoprenoid unit
NADH
-
both arms of the Escherichia coli complex I are widened after the addition of NADH but not of NADPH. NADH-induced conformational changes are also detected in solution
NADH
-
the enzyme is selective for NADH
NADH
-
the NADH binding site is located in the matrix of mitochondria and their inner membrane is impermeable for NADH
NADH
-
the adenosine moiety is crucial for binding, while the nicotinamide is detrimental to binding
NADH
-
binding of NADH includes interactions of the hydroxyl groups of the adenosine ribose with a conserved glutamic acid residue. Structural analysis revealed that due to steric hindrance and electrostatic repulsion, this residue most likely prevents the binding of NADPH, which is a poor substrate of the complex
NADPH
-
much higher affinity for NADH than for NADPH
NADPH
-
addition of NADH but not NADPH leads to an extension of the overall structure of the complex, although all cofactors of the complex are reduced by NADPH
Ubiquinone-10
-
the enzyme contains 4.2-4.5 mol of ubiquinone-10 per 650000 Da enzyme
iron-sulfur centre
-
-
additional information
-
no activity with NADPH
-
additional information
-
the enzyme contains only substoichiometric amounts of ubiquinone-9, 0.2-0.4 mol/mol
-
additional information
-
no activity with NADPH
-
additional information
-
[2Fe-2S] cluster N1a is not the reductant of O2 in complex I, but has a specific role in determining the outcome of O2 reduction
-
additional information
-
Ndi1p lacks iron sulfur clusters
-
additional information
-
NADPH is a poor substrate of the complex
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
dependent on
CaCl2
-
5-10 mM optimal for activity
Fe
-
enzyme contains Fe-S clusters
Fe
-
contains eight iron-sulfur clusters. Seven of them transfer electrons between the flavin and the quinone-binding site, and one is on the opposite side of the flavin. Reduction of the iron-sulfur clusters in mitochondrial NADH:ubiquinone oxidoreductase (complex I) by the very low potential reductant EuII-diethylenetriamine-N,N,N',N'',N''-pentaacetate
Fe
-
contains eight iron-sulfur clusters
Fe
-
signal shape and g values of cluster N4 [4Fe(G)C], are particularly sensitive to the changes of the environment around N4
Fe
-
iron-sulfur cluster N5 is coordinated by an HXXXCXXCXXXXXC motif in the NuoG subunit
Fe-S
-
contains two [2Fe-2S] clusters and six [4Fe-4S] clusters
Fe-S
-
-
Fe-S
-
contains 9 iron-sulfur clusters
Fe-S
-
nine iron-sulfur clusters
Fe2+
-
iron-sulfur center
Fe2+
-
8-9 FeS clusters per enzyme molecule, 8 of which are organized as a continuous eT chain connecting FMN and a ubiquinone binding site. Thermodynamic properties of FeS clusters, overview
Fe2+
-
Fe-S cluster, 29.0-0.37 of iron/1 mol of complex I
Iron
-
contains 4 major iron centers, contains 16-18 gatoms of iron per 650000 Da enzyme
Iron
-
enzyme contains Fe-S clusters; the NADH:ubiquinone oxidoreductase complex is composed of three distinct fragments: 1. IP: a water soluble Fe-S-protein that is composed of 5-6 polypeptides and contains four Fe-S clusters, 2. FP: a water-soluble Fe-S-flavoprotein that is composed of three polypeptides and contains FMN and two Fe-S clusters, 3. a water-insoluble fraction containing phospholipids and hydrophobic polypeptides
Iron
-
at least 4 different species of low-potential iron-sulfur clusters, characterization of the Fe-S clusters
Iron
-
contains 0.08 mol Fe per mol of flavin after dialysis
Iron
-
2 binuclear and 3 tetranuclear EPR detectable iron-sulfur clusters. Cluster N-1a is the most labile component among the five iron sulfur clusters; enzyme contains Fe-S clusters
Iron
-
one binuclear and three tetranuclear NADH-reducible iron-sulfur clusters
Iron
-
the enzyme contains at least 5 EPR-visible iron-sulfur clusters. The NQO3 subunits contains at least two distinct iron-sulfur clusters: 1 [2Fe-2S] cluster with axial EPR signals and a [4Fe-4S] cluster with rhombic symmetry. The midpoint redox potentials of [2Fe-2S] and [4Fe-4S] clusters at pH 8.6 is -472 mV and -391 mV, respectively
Iron
-
the enzyme contains at most nine putative iron-sulfur cluster binding sites, the NQO2 subunit bears a single [2Fe-2S] cluster, the NQO3 subunit contains multiple iron-sulfur clusters: one [2Fe-2S] cluster, one [4Fe-4S] cluster and possibly another [4Fe-4S] cluster
Iron
-
enzyme complex contains up to 8 iron-sulfur clusters, 2 * [2Fe-2S] and 6 * [4Fe-4S]
Iron
-
the CXXCXXXCX27C motif in the NQO3 subunit most likely ligates the [4Fe-4S] cluster
Iron
-
5 binuclear and three tetranuclear iron-sulfur clusters
Iron
-
the enzyme contains at least three iron-sulfur clusters
Iron
-
enzyme contains Fe-S clusters
Iron
-
contains approximately 0.06 mol of iron per mol of enzyme
Iron
-
contains no Fe-S clusters
Iron
-
enzyme contains 10.6 atoms of iron and 12.7 atoms of sulfur per dodecamer
NaCl
-
optimal concentration between 20 mM and 50 mM
[2Fe-2S]
-
four clusters in the NuoE subunit
[4Fe-4S]
-
-
[4Fe-4S]
-
two clusters in the NuoF subunit
Mg2+
-
required for activity
additional information
-
no FeS clusters are present in the protein
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxy-5-propyloctyl]octahydro-2,2'-bifuran-5-yl]-5-propylnonan-1-ol
-
IC50: 870 nM
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyethyl]octahydro-2,2'-bifuran-5-yl]undecan-1-ol
-
IC50: 280 nM
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyheptyl]octahydro-2,2'-bifuran-5-yl]pentadecan-1-ol
-
IC50: 34 nM
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyheptyl]octahydro-2,2'-bifuran-5-yl]undecan-1-ol
-
IC50: 3.2 nM
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxynonyl]octahydro-2,2'-bifuran-5-yl]tridecan-1-ol
-
IC50: 7.5 nM
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxypropyl]octahydro-2,2'-bifuran-5-yl]undecan-1-ol
-
IC50: 45 nM
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundec-3-yn-1-yl]octahydro-2,2'-bifuran-5-yl]dodec-4-yn-1-ol
-
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]dodecan-1-ol
-
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]undeca-3,5,7,9-tetrayn-1-ol
-
IC50: 0.000172 mM
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-5-ethyl-1-hydroxyoctyl]octahydro-2,2'-bifuran-5-yl]undecan-1-ol
-
IC50: 27 nM
(1R)-5-ethyl-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxy-5-propyloctyl]octahydro-2,2'-bifuran-5-yl]octan-1-ol
-
IC50: 1500 nM
(1R,1'R)-1,1'-((2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyl)-bis-(6-(4-n-butylphenoxy)hex-3-yn-1-ol)
-
-
(1R,1'R)-1,1'-((2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyl)-bis-(6-(4-n-butylphenoxy)hexan-1-ol)
-
-
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diylbis(5-[4-[(E)-(4-butylphenyl)diazenyl]phenoxy]pentan-1-ol)
-
48 nM, 70% inhibition
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diylbis(5-[4-[(Z)-(4-butylphenyl)diazenyl]phenoxy]pentan-1-ol)
-
48 nM, 70% inhibition
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diylbis[6-(2-butylphenoxy)hexan-1-ol]
-
IC50: 1000 nM
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diylbis[6-(4-butylphenoxy)hexan-1-ol]
-
IC50: 0.83 nM
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyldihexan-1-ol
-
IC50: 4500 nM
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyldioctan-1-ol
-
IC50: 45 nM
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyldiundecan-1-ol
-
IC50: 0.0000016 mM
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyldiundecan-1-ol
-
IC50: 1.6 nM
(1R,1'S)-1,1'-(2R,5R)-tetrahydrofuran-2,5-diylditridecan-1-ol
-
IC50: 0.025 mM
(1R,1'S)-1,1'-(2R,5R)-tetrahydrofuran-2,5-diylditridecan-1-ol
-
IC50: 9.0 nM
(5S)-3-[(10R)-10-hydroxy-10-[(2R,2'R,5R,5'R)-5'-[(1R)-1 hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]decyl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000012 mM
(5S)-3-[(13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-8-yn-1-yl]-5-methylfuran-2(5H)-one
-
; IC50: 0.00000083 mM
(5S)-3-[(13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]trideca-4,6,8,10-tetrayn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000017 mM
(5S)-3-[(13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1S)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-10-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.000001 mM
(5S)-3-[(13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1S)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-4-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.00000085 mM
(5S)-3-[(13R)-13-hydroxy-13-[(2R,5R)-5-[(1S)-1-hydroxytridecyl]tetrahydrofuran-2-yl]trideca-4,6,8,10-tetrayn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.00028 mM
(5S)-3-[(13R)-13-hydroxy-13-[(2R,5R)-5-[(1S)-1-hydroxytridecyl]tetrahydrofuran-2-yl]tridecyl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000023 mM
(5S)-3-[(13S)-13-hydroxy-13-[(2R,5R)-5-[(1S)-1-hydroxytriecyl]tetrahydrofuran-2-yl]tridecyl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000051 mM
(5S)-3-[(16R)-16-hydroxy-16-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]hexadecyl]-5-methylfuran-2(5H)-one
-
IC50: 0.000013 mM
(5S)-3-[(19R)-19-hydroxy-19-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]nonadecyl]-5-methylfuran-2(5H)-one
-
IC50: 0.000271 mM
(5S)-3-[(2E,13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-2-en-4-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000011 mM
(5S)-3-[(5R)-5-hydroxy-5-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]pentyl]-5-methylfuran-2(5H)-one
-
IC50: 0.000014 mM
(5S)-3-[(7E,13S)-13-hydroxy-13-[(2R,5R)-5-[(1S)-1-hydroxytridecyl]tetrahydrofuran-2-yl]tridec-7-en-9-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000052 mM
(5S)-3-[(8E,13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1S)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-8-en-10-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.00000092 mM
(5S)-3-[(8R)-8-hydroxy-8-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]octyl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000016 mM
(5S)-3-[4-[(E)-(4-[[(4R)-4-hydroxy-4-[(2R,5R)-5-[(1R)-1-hydroxytridecyl]tetrahydrofuran-2-yl]butyl]oxy]phenyl)diazenyl]benzyl]-5-methylfuran-2(5H)-one
-
-
(5S)-3-[4-[(E)-(4-[[(7R)-7-hydroxy-7-[(2R,5R)-5-[(1R)-1-hydroxytridecyl]tetrahydrofuran-2-yl]heptyl]oxy]phenyl)diazenyl]benzyl]-5-methylfuran-2(5H)-one
-
-
(5S)-3-[4-[(Z)-(4-[[(4R)-4-hydroxy-4-[(2R,5R)-5-[(1R)-1-hydroxytridecyl]tetrahydrofuran-2-yl]butyl]oxy]phenyl)diazenyl]benzyl]-5-methylfuran-2(5H)-one
-
-
(5S)-3-[4-[(Z)-(4-[[(7R)-7-hydroxy-7-[(2R,5R)-5-[(1R)-1-hydroxytridecyl]tetrahydrofuran-2-yl]heptyl]oxy]phenyl)diazenyl]benzyl]-5-methylfuran-2(5H)-one
-
-
1-Geranyl-2-methylbenzimidazole
-
0.001 mM, 87% inhibition
1-hydroxy-2-octyl-4(1H)quinolone
-
-
1-methyl-4-phenylpyridinium
-
complex I inhibitor, which has no effect on mediobasal hypothalamic tuberoinfundibular dopamine neurons, but significantly increases the percentage of apoptag immunoreactive neurons in midbrain primary nigrostriatal dopamine and mesolimbic dopamine cultures
1-methyl-4-phenylpyridinium ion
-
inhibition of mitochondrial complex I. Neuroprotective effects of caffeine in the MPP+ model of apoptosis are mediated through activation of the ataxia telangiectasia mutated enzyme/p53 pathway. Caffeine decreases the expression of cyclin D and the transcription factor E2F-1, a regulator of apoptosis in neurons. Caffeine-mediated neuroprotection is not mediated through blockade of adenosine receptors because DPCPX and CGS-15943, two antagonists of these receptors, fail to attenuate apoptosis produced by 1-methyl-4-phenylpyridinium ion treatment
2',3'-dideoxycytidine
-
0.001 mM prevents the phosphorylation of the NDUFB11 subunit of complex I
2,3-dimethoxy-5-methyl-6-[(6-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
-
0.00028 mM, NADH-coenzyme Q1 activity
2,6-dichlorophenolindophenol
-
-
2-(4-butylbenzylamino)-3-methylchromen-4-one
-
-
2-(4-butylbenzyloxy)-3-methylchromen-4-one
-
-
2-decyl-4-quinazolinyl amine
-
-
2-decyl-4-quinazolinyl amine
-
0.00022 mM
2-decyl-4-quinazolinyl amine
-
0.002 mM, strong inhibitor
2-decyl-4-quinazolinyl amine
-
the compound is both a complex I inhibitor and an uncoupler
2-n-decyl-4-quinazolinylamine
-
0.001 mM, 73% inhibition
2-n-decyl-quinazoline-4-yl-amine
-
IC50: 0.0004 mM
2-[(2,6-dimethylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
0.00077 mM, NADH-coenzyme Q1 activity
2-[(4-butylbenzyl)sulfanyl]-3-methyl-4H-chromen-4-one
-
-
2-[(6-chloro-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
0.00065 mM, NADH-coenzyme Q1 activity
2-[(6-chloro-2-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
0.00025 mM, NADH-coenzyme Q1 activity
2-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
0.00096 mM, NADH-coenzyme Q1 activity
2-[4-(4-fluorobutyl)benzylamino]-3-methylchromen-4-one
-
-
2-[4-(4-fluorobutyl)benzyloxy]-3-methylchromen-4-one
-
-
2-[4-(4-fluorobutyl)benzylsulfanyl]-3-methylchromen-4-one
-
most potent inhibitor. 30 min after high uptake of the radiotracer from the blood pool into the myocardium, kidney, and liver. After 2 h about 66% of the activity in the myocardium at 30 min has been retained, whereas ca. 70% has been cleared from the liver and kidney
3'-azido-3'-deoxythymidine
-
0.01 and 0.05 mM prevent the phosphorylation of the NDUFB11 subunit of complex I. This is associated with a decrease in complex I activity
3'-azido-3'-deoxythymidine monophosphate
-
0.15 mM prevents the phosphorylation of the NDUFB11 subunit of complex I. This is associated with a decrease in complex I activity
3,3'-methylene-bis(4-hydroxycoumarin)
-
-
3-azido-ubiquinone-2
P17694
-
-
3-azido-ubiquinone-2
-
-
-
37-methoxyquinoxalinone
-
IC50: 10 nM
39-pyridopyrazinone
-
IC50: 17 nM
4-(4-benzyl-phenoxy)-N-(3,4-dimethoxy-benzyl)-benzamide
-
-
4-(4-tert-butyl-phenoxy)-N-(3,4-dimethoxy-benzyl)-benzamide
-
-
5-(N-ethyl)-N-isopropylamiloride
-
IC50 : 0.1 mM
5-(N-ethyl-N-isopropyl)amiloride
-
-
5BM-GX
-
inhibits transhydrogenation reaction with NADH and 3'-acetyl pyridine adenine dinucleotide
6-amino-4-(4-tert-butylphenethylamino)quinazoline
P17694
-
-
6-amino-4-(4-tert-butylphenethylamino)quinazoline
-
-
-
6-azido-4-(4-iodophenethylamino)quinazoline
P17694
the compound specifically binds to the 49000 Da and ND1 subunits with a frequency of about 4:1
-
6-azido-4-(4-iodophenethylamino)quinazoline
-
the compound specifically binds to the 49000 Da and ND1 subunits with a frequency of about 4:1
-
6-azido-N-[2-(4-tert-butylphenyl)ethyl]-6,7-dihydroquinazolin-4-amine
P17694
-
9-amino-6-chloro-2-methoxyacridine
-
0.0005 mM
ADP-ribose
-
competitive with NADH
ADP-ribose
-
ADP-ribose acts as mixed-type inhibitors for NADH, ferricyanide and 5,8-dioxy-1,4-naphthoquinone
AMP
-
dead-end inhibitor, linear competitive inhibitor of NADH, linear uncompetitive inhibitor of oxidized 2,6-dichlorophenol indophenol
AMS-GX
-
inhibits transhydrogenation reaction with NADH and 3'-acetyl pyridine adenine dinucleotide
Amytal
-
0.5 mM, 50% inhibition
antimycin A
-
0.0009 mM
arylazido-beta-alanyl-NAD+
-
competitive inhibition towards NADH and ferricyanide
-
atovaquone
-
20 nM, complete inhibition of partially purified enzyme. Inhibition of complex I represents a likely mechanism of the known antileishmanial activity of the drug
Ba2+
-
1 mM
Barbiturates
-
-
-
benzamil
-
IC50: 0.07 mM
benzimidazole
-
0.001 mM, 72% inhibition
benzo (1,2,3) thiadiazole-7-carbothioic acid S-methyl ester
-
0.075 mM, strong inhibition
benzoxazinone
-
0.001 mM, 76% inhibition
bis-tetrahydrofuran acetogenin
-
the additional methylenes enhance the hydrophobicity of the spacer region, which may be thermodynamically advantageous for bringing the polar gamma-lactone ring into the membrane-embedded segment of complex I
-
bullatacin
-
IC50: 0.00000083 mM
bullatacin
-
potent inhibitor
bullatacin
P17694
-
Ca2+
-
1 mM
Ca2+
-
inhibits complex I activity in a concentration-dependent manner. Ca2+ acts specifically on complex I. Complex I inactivation by Ca2+ results in reduction of NADH-supported electron transport activity and suppression of the rate of O2- production
CaCl2
-
50 mM or greater
capsaicin
-
and synthetic capsaicin analogue. Several synthetic capsaicins discriminate between NDH-1 and NDH-2 much better than natural capsaicin
capsaicin
-
no inhibition of enzymes where the energy couling site is absent
capsaicin
-
inhibition of enzymes involved in energy coupling site
capsaicin
-
no inhibition of enzymes where the energy couling site is absent
capsaicin
-
inhibition of enzymes involved in energy coupling site
capsaicin
-
0.3 mM, 88% inhibition
capsaicin
-
-
capsaicin-40
-
0.01 mM
carbonyl-cyanide-p-trifluoro-methoxy-phenylhydrazone
-
0.001 mM
carvedilol
-
decreases mitochondrial complex I activity, which is associated with an increase in mitochondrial H2O2 production, total glutathione and protein thiols content
Cd2+
-
1 mM, potent inhibitor
Co2+
-
1 mM
Cu2+
-
1 mM
Demerol
-
-
dicyclohexylcarbodi-imide
-
90% inhibition, IC50: 0.25 mM
Dicyclohexylcarbodiimide
-
-
diphenyl iodonium
-
maximal inhibition after preincubation with NADH, more complete inhibition with the more hydrophobic electron acceptors such as ubiquinone-1 or ubiquinone-2 as electron acceptor compared to the more hydrophilic ones, such as ubiquinone-0 or dichloroindophenol
diphenyl iodonium chloride
-
0.001 mM and above
diphenyleineiodonium
-
does not inhibit superoxide generation
diphenylene iodinium chloride
-
-
diphenylene iodonium
-
75% inhibition, IC50: 0.013 mM
diphenylene iodonium chloride
-
0.001 mM and above
diphenyleneiodonium
-
strongly inhibits superoxide production by complex I driven by reverse electron transport from succinate. Inhibition of superoxide production is not dependent on changes in the pH gradient. The inhibitor does not react with the flavin of complex I
-
DL-homocysteic acid
-
marked (ca. 64%) decrease of respiratory chain complex I activity in the cerebral cortex of immature rats following seizures induced by bilateral intracerebroventricular infusion of DL-homocysteic acid (600 nanomol/side). Decrease is already evident during the acute phase of seizures (60-90 min after infusion) and persists for at least 20 h after the seizures. Inhibition is selective for complex I since activities of complex II and IV and citrate synthase remain unaffected. Inhibition of complex I activity is not associated with changes in complex I content. Enhanced production of reactive oxygen species by inhibited complex I in mitochondria from DL-homocysteic acid-treated animals. Competitive NMDA receptor antagonist AP7, a selective and potent group II mGluR agonist (2R,4R)-APDC and a highly selective group III mGluR, subtype 8, agonist (S)-3,4-DCPG, significantly reduce the extent of complex I inhibition. The superoxide dismutase mimetic Tempol and a selective peroxynitrite scavenger and decomposition catalyst FeTPPS provide a significant attenuation of complex I inhibition associated with DL-homocysteic acid-induced seizures
Dodecyl-beta-D-maltoside
-
leads to immediate loss of activity
Doxorubicin
-
; maximal inhibition at 0.001 mM
fenpyroximate
P17694
-
-
fenpyroximate
-
-
-
fenpyroximate
-
deactive but not active complex I is a Na+/H+ antiporter that can be inhibited by fenpyroximate
-
ferricyanide
-
inhibits the interaction of the oxidized enzyme with NADH
flavone
-
0.165 mM, 50% reduction of activity with duroquinone
flavone
-
insensitive to
flavone
-
dead-end inhibitor; partial inhibitor displaying a hyperbolic uncompetitive inhibition with respect to oxidized 2,6-dichlorophenol indophenol
flutamide
-
inhibits complex I of the electron transport chain to a greater extent than a nitro to cyano analogue of flutamide. As compared to the nitro to cyano analogue of flutamide, the nitroaromatic group of flutamide enhances cytotoxicity to hepatocytes, likely through mechanisms involving mitochondrial dysfunction and ATP depletion that include complex I inhibition
-
imidazole
-
0.001 mM, 75% inhibition
liponox DCH
-
inhibitory at concentrations higher than 0.02%
-
Mersalyl
-
0.3 mM, 77% inhibition of NADH-ubiquinone-1 reductase activity, 96% inhibition of NADH-potassium ferricyanide reductase activity
metformin
-
inhibits complex I activity, associated with LPS-induced neutrophil activation. Metformin prevents LPS-induced acute lung injury
Mg2+
-
inhibition of the enzyme in its inactive form, in its active form the enzyme complex is not sensitive
Mn2+
-
1 mM
Myxothiazol
-
IC50: 170 nM
Myxothiazol
-
complex I Q-reduction site inhibitor
N,N'-dicyclohexylcarbodiimide
-
2 mM, 71% inhibition
N-(3,4-dimethoxy-benzyl)-4-[4-(1,1-dimethyl-propyl)-phenoxy]-benzamide
-
-
N-ethylmaleimide
-
0.5 mM, strong inhibition
NAD+
-
4 mM, 19% inhibition of NADH-ubiquinone-1 reductase activity
NAD+
-
product inhibition
NAD+
-
weak inhibitor
NAD+
-
NAD+ acts as a mixed-type inhibitor for both substrates in the NADH: ferricyanide reductase reaction of complex I
NAD+
-
NAD+ acts as mixed-type inhibitors for NADH, ferricyanide and 5,8-dioxy-1,4-naphthoquinone. At saturating concentrations of oxidizer, NAD+ acts as a competitive inhibitor for NADH
NADH
-
inhibits the interaction of the reduced enzyme with ferricyanide
NADH
-
NADH acts as a competitive inhibitor for ferricyanide, the reactions of with quinones and nitro compounds are not inhibited by NADH
NADH
-
NADH acts as a competitive inhibitor for 5,8-dioxy-1,4-naphthoquinone, NADH acts as a linear competitive inhibitor for ferricyanide
NEM
-
inhibition of the enzyme in its inactive form, in its active form the enzyme complex is not sensitive
Ni2+
-
1 mM, potent inhibitor
nigericin
-
0.0125 mM
otivarin
-
-
oxygen
-
O2 induces self-inactivation of the enzyme via the formation of protein radicals
p-Chloromercuriphenyl sulfonic acid
-
0.1 mM, 50% inhibition
palmitate
-
IC50: 0.009 mM, at 25C and pH 8.0
piercidin
-
-
piercidin A
-
-
piericidin
-
the residual activity in the presence of saturating palmitate is completely (>90%) inhibited by piericidin
piericidin
-
complex I Q-reduction site inhibitor
piericidin
-
specific inhibitor of ubiquinone reduction
Piericidin A
-
0.0023 mM
Piericidin A
-
IC50: 0.0000013 mM
Piericidin A
-
degree of inhibition for the reaction with decylubiquinone is higher than for the reaction with ubiquinone-1 as electron acceptor
Piericidin A
-
-
Polymyxin B
-
in the presence of polymyxin B, enzyme kinetics changes from the MichaelisMenten type to substrate inhibition kinetics with the substrate inhibition
pyridabene
P17694
-
-
quinoxalinone
-
0.001 mM, 79% inhibition
reduced 2,6-dichlorophenolindophenol
-
-
reduced coenzyme Q1
-
product inhibition
Rhein
-
i.e. 4,5-dioxy-anthraquinone-z-carbonic acid, competes for a NADH-binding site
rolliniastatin
-
strong inhibitor
rolliniastatin
-
-
rolliniastatin-1
-
-
rolliniastatin-2
-
-
rolliniastatin-2
-
0.001 mM, 92% inhibition
rotenone
-
mitochondria contain two different NADH:ubiquinone reductases. One enzyme oxidizes endogenous NADH, couples electron transfer to proton translocation and is inhibited by rotenone, the other enzyme oxidizes exogenous NADH without proton tranlocation and is insensitive to rotenone. The activity of the rotenone-insensitive enzyme highly exceeds the activity of the rotenone-sensitive enzyme
rotenone
-
rotenone-insensitive enzyme
rotenone
-
strong
rotenone
-
rotenone-insensitive enzyme
rotenone
-
IC50: 0.002 mM
rotenone
-
inhibition of NADH oxidation, NAD+ reduction is not inhibited by 0.001 mM rotenone
rotenone
-
150 nM, 85% inhibition in presence of 0.01 mM NADH, inhibition is independent of coenzyme Q1 concentration below 0.05 mM, rotenone sensitivity decreases significantly with coenzyme Q1 concentration above 0.1 mM
rotenone
-
0.001-0.01 mM, 50-75% inhibitio in mitochondrial lysate. Inhibition of complex I represents a likely mechanism of the known antileishmanial activity of the drug
rotenone
-
0.00025 mM
rotenone
-
0.001 mM, 90% inhibition
rotenone
-
0.01 mM, complete inhibition
rotenone
-
0.001 mM
rotenone
-
0.002 mg/ml
rotenone
-
does not inhibit superoxide generation
rotenone
-
100 nM, complete inhibition
rotenone
-
inhibits complex I, which is associated with increased ROS generation, LPS-induced nuclear translocation of NF-kappaB and cytokine production in neutrophils. Rotenone pretreatment attenuates LPS-induced acute lung injury
rotenone
-
RCC-I inactivation causes a dramatic decrease in mitochondrial NO that is not affected by Mn (III) porphyrin 5,10,15,20-tetrakis(benzoic acid) porphyrin. RCC-I inactivation drastically increases mitochondrial reactive oxygen species, which is prevented when mitochondrial nitric oxide synthase is inhibited or cells are treated with Mn (III) porphyrin 5,10,15,20-tetrakis(benzoic acid) porphyrin. Inactivation of RCC-I in SHSY cells dramatically increases tyrosine nitration of mitochondrial proteins that is fully prevented when mitochondrial nitric oxide synthase is inactivated. RCC-I inactivation leads cytochrome c to diffuse into the cytoplasm indicating its release from the mitochondria
rotenone
-
when RCC-I is inactivated, mitochondrial nitric oxide synthase stimulation dramatically augments the superoxide signal, whereas augmented superoxide signal is prevented when mitochondrial nitric oxide synthase is inhibited and abolished by superoxide dismutase. RCC-I inactivation dramatically increases S-nitrosoglutathione decomposition that is prevented when mitochondrial nitric oxide synthase is inhibited. RCC-I inactivation increases tyrosine-nitrated mitochondrial proteins, causes cytochrome c release and aggregation of mitochondria
rotenone
-
decreases complex I activity by 25%, 27% and 48% in the presence of 0.005, 0.01 and 0.02 mM carvedilol, respectively
rotenone
-
when complex I activity is chronically reduced by 80% using 100 nanomol rotenone, the percentage of moving mitochondria decreases from 79% to 50% and reduce their velocity by 30%
rotenone
-
reduces complex I activity, which is accompanied by increasing production of cellular superoxide
rotenone
-
strongly inhibits superoxide production by complex I
rotenone
-
is a more potent inhibitor of complex I than flutamide. Inhibits complex I of the electron transport chain to a greater extent than a nitro to cyano analogue of flutamide
rotenone
-
rotenone-induced increment of H2O2 production is 2fold higher upon DL-homocysteic acid-treatment, thus clearly indicating elevated production of reactive oxygen species at complex I
rotenone
-
completely obstructs electron transfer through complex I
rotenone
-
inhibits complex I followed by apoptosis. 40% decrease of dopamine content suppresses rotenone-induced apoptosis. 30% increase of dopamine content by inhibition of dopamine metabolism enhances rotenone-induced apoptosis. Depletion of intracellular dopamine using reserpine (0.0001-0.01 mM) also prevents rotenone-induced apoptosis, and this effect is counteracted by dopamine (0.01-0.1 mM) replenishment. Inhibition of dopamine reverse transport increases cytosolic dopamine and enhances rotenone-induced apoptosis. Rotenone induces dopamine redistribution from vesicles to the cytosol. Rotenone stimulates reactive oxygen species and protein carbonylation and decreases the antioxidant glutathione. Addition of the antioxidant N-acetylcysteine (3 mM), prevents dopamine being expelled from vesicles and inhibits rotenone-induced apoptosis
rotenone
-
complex I inhibitor, which has no effect on mediobasal hypothalamic tuberoinfundibular dopamine neurons, but significantly increases the percentage of apoptag immunoreactive neurons in midbrain primary nigrostriatal dopamine and mesolimbic dopamine cultures
rotenone
-
0.002 mM rotenone diminishes the bimolecular rate constant value for tetramethyl-1,4-benzoquinone and for 2,5-dimethyl-1,4-benzoquinone by 30 and 10%, respectively
rotenone
-
specific inhibitor of ubiquinone reduction
rotenone
-
deactive but not active complex I is a Na+/H+ antiporter that can be inhibited by rotenone
salicylic acid
-
0.5 mM, 45% inhibition
Sodium azide
-
10 mM
squamocin
-
-
squamocin
-
0.001 mM, 88% inhibition
squamocin M
-
IC50: 0.00000085 mM
squamocin-quinoxalinone
-
-
squamocin-triazine
-
-
Stigmatellin
-
0.001 mM
Trifluoperazine
-
0.05 mM
Triton X-100
-
specific inhibitor of ubiquinone reduction by complex I
Triton X-100
-
leads to immediate loss of activity
vanillylnonanamide
-
0.4 mM
Zn2+
-
pH-dependent potent inhibitor, IC50: 0.01-0.05 mM at pH 7.5, depending on the enzyme state, Zn2+ does not inhibit NADH oxidation or intramolecular electron transfer, so it probably inhibits either proton transfer to bound quinone or proton translocation.
[2-(4-butyl)benzylsulfanyl]-3-methylchromen-4-one
-
-
molvizarin
-
-
-
additional information
-
no inhibition by rotenone up to 0.25 mM and flavone
-
additional information
-
insensitive to rotenone
-
additional information
-
insensitive to 0.5 mM 5,5-dithiobis-(2-nitrobenzoate) and 10 mM oxidized glutathione at pH 8.0
-
additional information
-
in m.1627A animals, the enzyme activity value under normal oxygen is significantly higher than that under simulated hypoxia
-
additional information
-
COX I mutant cybrids show a 80% reduction in complex I enzymatic activity in isolated mitochondria as compared with control cybrids
-
additional information
-
mouse cell lines with suppressed expression of the nuclearly encoded subunit 4 of complex IV associated with a loss of assembly of complex IV show significantly reduced level of assembled complex I and activity, whereas levels and activity of complex III are normal or up-regulated
-
additional information
-
inhibition of mitochondrial complex I by serum and potassium deprivation. Caffeine does not exert neuroprotective effects after serum and potassium withdrawal, a p53-independent model of apoptosis
-
additional information
-
no inhibition: dibenziodolium chloride, diphenyliodonium chloride, 1-hydroxy-2-dodecyl-4(1H)quinolone, atovaquone, antimycin A, rotenone, flavone, artemisinin
-
additional information
-
not inhibited by ferricyanide above 1 mM
-
additional information
-
the oxidation of NADH by 5,8-dioxy-1,4-naphthoquinone, catalyzed by complex I is completely insensitive to 0.002 mM rotenone
-
additional information
-
inhibition of flavin-site reactions by NADH analogues and fragments, overview
-
additional information
-
when NADH, ADP, ATP and ADP-ribose bind to the reduced flavin they stimulate paraquat and HAR reduction, but inhibit FeCN, APAD+ and O2 reduction
-
additional information
-
capsaicin, the DELTAlac-acetogenin, 1-methyl-4-phenyl-pyridinium, piericidin A, ranolazine, and stigmatellin have no effect on the antiporter activity, whereas fenpyroximate (as well as rotenone) inhibited it
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ADP
-
4.5fold activation of NADH:ubiquinone oxidoreductase at 0.1 M
ADP-ribose
-
-
alamethicin
-
slight stimulation
asolectin
-
activation by detergent solubilized asolectin
-
asolectin
-
-
-
ATP
-
10fold activation of NADH:ubiquinone oxidoreductase at 0.1 M, ATP in the micromolar concentration range specifically stimulates the NADH:hexaammineruthenium(III) (HAR) reductase activity catalyzed by eukaryotic complex I when assayed at low NADH and acceptor concentrations
ATP
-
ATP in the micromolar concentration range specifically stimulates the NADH:hexaammineruthenium(III) (HAR) reductase activity catalyzed by eukaryotic complex I when assayed at low NADH and acceptor concentrations
Dodecyl maltoside
-
strong stimulation of activity
FAD
-
0.1 mM, about 2fold stimulation
L-Dopa
-
enhances nigral mitochondrial complex I expression and activity. Significant increase at 6 h, with maximal values at 24 h, compared with control animals, in absence of concomitant changes in the expression or activity of complex IV
liponox DCH
-
required at 0.02% for optimum activity
-
pyruvate
-
when RCC-I is activated, mitochondrial superoxide is decreased by mitochondrial nitric oxide synthase stimulation, whereas decreased superoxide is prevented when mitochondrial nitric oxide synthase is inhibited. RCC-I activation increases mitochondrial S-nitrosoglutathione that is further increased by mitochondrial nitric oxide synthase stimulation and prevented when mitochondrial nitric oxide synthase is inhibited
riboflavin
-
0.001 mg/ml
rotenone
-
chronic rotenone treatment (100 nanomol, 72 h) increases fully assembled complex I in human skin fibroblasts
malate
-
when RCC-I is activated, mitochondrial superoxide is decreased by mitochondrial nitric oxide synthase stimulation, whereas decreased superoxide is prevented when mitochondrial nitric oxide synthase is inhibited. RCC-I activation increases mitochondrial S-nitrosoglutathione that is further increased by mitochondrial nitric oxide synthase stimulation and prevented when mitochondrial nitric oxide synthase is inhibited
additional information
-
brief exposure of the thermally deactivated mitochondria with malate/glutamate, NAD+ and cytochrome c induced reactivation of the inactivated enzyme, exposure to 37C induces deactivation of complex I
-
additional information
-
the enzyme exists in two kinetically and structurally distinct slowly interconvertible forms, active form A and de-activated form D. Continous slow cycling between form A and form D occurs during the steady-state operation of complex I in the mitochondria
-
additional information
-
in m.1627C animals, the enzyme activity value under normal oxygen is significantly lower than that under simulated hypoxia
-
additional information
-
positions C67, H149 and H322 of NDUFA10 are specially targeted by different modifications suggesting the high reactivity of these residues and their potential implication in the regulation of the protein function. Accumulation of R, K and H methylations and probably K acetylations at the C-terminal region that may play a role in the control of NDUFA10 activity
-
additional information
-
no activation by adenylylimidodiphosphate, GTP, GDP, adenosine, AMP, cAMP, and CTP
-
additional information
-
no stimulation of the three-subunit FP fragment of complex I or for membrane-bound NDH-1 by ATP
-
additional information
-
NADH, ATP, ADP and ADP-ribose stimulate the enzyme reactions, indicating that the positively-charged acceptors interact with their negatively charged phosphates. In contrast to direct O2 reduction the rate is stimulated, not inhibited, by high NADH concentrations. When NADH, ADP, ATP and ADP-ribose bind to the reduced flavin they stimulate paraquat and HAR reduction, but inhibit FeCN, APAD+ and O2 reduction. Adenosine, which lacks phosphates, does not stimulate the reaction with hexaammineruthenium(III), HAR, ternary mechanism of HAR and paraquat reduction,overview
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.55
-
1,1'-carbamoylmethylviologen
-
-
1
-
1,1'-carbamoylmethylviologen
-
-
0.4
-
1,4-benzoquinone
-
pH 7.0, 25C
0.0434
-
2,3-dimethoxy-5-methyl-6-[(6-methyl-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
-
-
0.3598
-
2,3-dimethoxy-5-methyl-6-[(6-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
-
-
0.0417
-
2,3-dimethoxy-5-methyl-6-[(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
-
-
0.4
-
2,5-dimethyl-1,4-benzoquinone
-
pH 7.0, 25C
0.0062
-
2,6-dichlorophenolindophenol
-
-
0.016
-
2,6-dichlorophenolindophenol
-
-
0.55
-
2,6-dichlorophenolindophenol
-
-
0.03348
-
2-[(2,6-dimethylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
0.221
-
2-[(2-chloro-6-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
0.01683
-
2-[(2-chloro-6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
0.4144
-
2-[(6-chloro-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
0.417
-
2-[(6-chloro-2-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
0.227
-
2-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
0.125
-
3'-acetyl pyridine adenine dinucleotide
-
pH 8.0, 26C
0.08
-
5,8-dioxy-1,4-naphthoquinone
-
pH 7.0, 25C
-
0.12
-
5-oxy-1,4-naphthoquinone
-
pH 7.0, 25C
-
0.09
-
9,10-phenanthrenequinone
-
pH 7.0, 25C
0.1
-
benzoquinone
-
-
0.065
-
coenzyme Q0
-
-
0.01
-
coenzyme Q1
-
pH 8.0, 25C
0.0129
-
coenzyme Q1
-
-
0.015
-
coenzyme Q1
-
pH 8.0, 25C
0.02
-
coenzyme Q1
-
pH 8.0, 25C
0.024
-
coenzyme Q1
-
-
0.297
-
coenzyme Q10
-
-
0.012
-
cytochrome c
-
-
0.036
-
cytochrome c
-
in the presence of 0.1 mM daunorubicin
0.0571
-
cytochrome c
-
in the presence of 0.1 mM mitoxantrone
0.0684
-
cytochrome c
-
in the presence of 0.1 mM ametantrone
0.0004
-
deamino-NADH
-
pH 8.0, 26C
0.024
-
decylubiquinone
-
using 0.1 mM NADH at pH 7.5
0.066
-
decylubiquinone
-
-
2
3
decylubiquinone
-
mutant enzyme V206E; mutant enzyme Y229H
25
-
decylubiquinone
-
mutant enzyme H210T
33
-
decylubiquinone
-
mutant enzyme D213E
34
-
decylubiquinone
-
mutant enzyme D213N
37
-
decylubiquinone
-
mutant enzyme R209F
40
-
decylubiquinone
-
mutant enzyme E228D
43
-
decylubiquinone
-
mutant enzyme E216A; wild type enzyme
0.489
-
duroquinone
-
-
0.055
-
ferricyanide
-
-
0.4
-
ferricyanide
-
-
4
-
ferricyanide
-
-
0.002
-
menadione
-
pH 7.5, 30C
0.239
-
menadione
-
pH 8.0, 25C
0.007
-
n-decylubiquinone
-
mutant P232G (49000 Da subunit)
0.012
-
n-decylubiquinone
-
mutant T157I (30000 Da subunit)
0.014
-
n-decylubiquinone
-
mutant R211W (30000 Da subunit)
0.016
-
n-decylubiquinone
-
mutant D228Q (49000 Da subunit)
0.017
-
n-decylubiquinone
-
mutant S416P (49000 Da subunit)
0.021
-
n-decylubiquinone
-
mutant F87L (49000 Da subunit)
0.029
-
n-decylubiquinone
-
mutant R231E (49000 Da subunit)
0.039
-
n-decylubiquinone
-
mutant S416A (49000 Da subunit)
0.007
-
NAD+
-
pH 8.0, 25C, succinate supported NAD+ reduction
0.27
-
NAD+
-
pH 8.0, 25C, succinate supported NAD+ reduction
5e-05
-
NADH
-
apparent value, for superoxide production, at 32C and pH 7.5
0.001
-
NADH
-
-
0.0014
-
NADH
-
coupled oxidase reaction, pH 8.0, 25C
0.00172
-
NADH
-
with 0.01 mM coenzyme Q1
0.00195
-
NADH
-
with 0.025 mM coenzyme Q1
0.002
-
NADH
-
coupled oxidase reaction, pH 8.0, 25C
0.002
-
NADH
-
with 0.05 mM coenzyme Q1
0.0022
-
NADH
-
uncoupled oxidase reaction, pH 8.0, 25C
0.0027
-
NADH
-
pH 8.0, 26C
0.005
-
NADH
-
in the presence of 1 mM ferricyanide
0.0051
-
NADH
-
using decylubiquinone as substrate
0.0057
-
NADH
-
mutant E183H, pH 6.0, 30C
0.0058
-
NADH
-
mutant E183D, pH 6.0, 30C
0.006
-
NADH
-
uncoupled oxidase reaction, pH 8.0, 25C
0.007
-
NADH
-
reaction with ferricyanide
0.007
-
NADH
-
uncoupled oxidase reaction, pH 8.0, 25C
0.01
-
NADH
-
-
0.0116
-
NADH
-
at pH 7.0
0.012
-
NADH
-
-
0.012
-
NADH
-
mutant E183Q, pH 6.0, 30C
0.013
-
NADH
-
wild-type enzyme, pH 6.0, 30C
0.014
-
NADH
-
reaction with cytochrome c
0.014
-
NADH
-
-
0.014
-
NADH
-
mutant E183N, pH 6.0, 30C
0.0167
-
NADH
-
using ubiquinone-1 as substrate
0.019
-
NADH
-
reaction with ubiquinone-1
0.031
-
NADH
-
with ubiquinone-6 as acceptor
0.0438
-
NADH
-
enzyme activated before assay, electron acceptor: ferricyanide
0.0452
-
NADH
-
electron acceptor: ferricyanide
0.0483
-
NADH
-
enzyme activated before assay, electron acceptor: ubiquinone-1
0.094
-
NADH
-
pH 7.6, 32C, cosubstrate: ubiquinone-1, ubiquinone-0 or idebenone
0.0965
-
NADH
-
electron acceptor: ubiquinone-1
0.132
-
NADH
-
pH 7.5, 30C
0.025
-
NADPH
-
mutant E183H, pH 6.0, 30C
0.045
-
NADPH
-
mutant E183Q, pH 6.0, 30C
0.39
-
NADPH
-
mutant E183D, pH 6.0, 30C
0.48
-
NADPH
-
mutant E183N, pH 6.0, 30C
1.8
-
NADPH
-
-
1.87
-
NADPH
-
wild-type enzyme, pH 6.0, 30C
0.05
-
naphthoquinone
-
-
0.0046
-
oxidized dichlorophenolindophenol
-
pH 8.0, 25C
-
0.104
-
ubiquinone-0
-
pH 8.0, 25C
0.35
-
ubiquinone-0
-
-
0.002
-
ubiquinone-1
-
pH 8.0, 25C
0.0041
-
ubiquinone-1
-
at pH 7.0
0.015
-
ubiquinone-1
-
pH 7.4, 25C
0.04
-
ubiquinone-1
-
-
0.143
-
ubiquinone-1
-
-
0.4
-
ubiquinone-1
-
-
0.0032
-
ubiquinone-2
-
at pH 7.0
0.01
-
ubiquinone-2
-
-
0.0204
-
ubiquinone-2
-
using 0.1 mM NADH at pH 7.5
0.083
-
ubiquinone-2
-
-
0.1
-
menaquinone
-
-
additional information
-
additional information
-
Km-value for NADH, decylubiquinone, coenzyme Q1 and coenzyme Q2 are measured at different concentrations of the cosubstrate
-
additional information
-
additional information
-
Km-values for decylubiquinone are measured at pH-values 6.5 and 9.0 at different concentrations of the cosubstrate NADH. Km-values for NADH are measured at pH values 6.5, 7.0, 7.5, 8.0, 8.5 and 9.0 and at different concentrations of the cosubstrate decylubiquinone
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
8.33
-
2,3-dimethoxy-5-methyl-6-[(6-methyl-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
-
-
81.73
-
2,3-dimethoxy-5-methyl-6-[(6-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
-
-
23.88
-
2,3-dimethoxy-5-methyl-6-[(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]benzo-1,4-quinone
-
-
11.22
-
2-[(2,6-dimethylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
42.95
-
2-[(2-chloro-6-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
25.8
-
2-[(2-chloro-6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
63.46
-
2-[(6-chloro-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
76.28
-
2-[(6-chloro-2-methylimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
62.82
-
2-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)methyl]-5,6-dimethoxy-3-methylbenzo-1,4-quinone
-
-
47.69
-
coenzyme Q0
-
-
211.5
-
coenzyme Q1
-
-
1500
-
hexaammineruthenium-III-chloride
-
-
0.077
-
menadione
-
pH 8.0, 25C
2
8
NADH
-
mutant E183Q, pH 6.0, 30C
2.7
-
NADH
-
pH 7.6, 32C, cosubstrate: ubiquinone-1, ubiquinone-0 or idebenone
11
-
NADH
-
mutant E183N, pH 6.0, 30C
26
-
NADH
-
wild-type enzyme, pH 6.0, 30C
37
-
NADH
-
mutants E183D and E18H, pH 6.0, 30C
80
100
NADH
-
with ubiquinone-6 as acceptor, Triton assay medium
500
550
NADH
-
with ubiquinone-6 as acceptor, mitochondria
3
-
NADPH
-
wild-type enzyme, pH 6.0, 30C
10
-
NADPH
-
mutant E183H, pH 6.0, 30C
11
-
NADPH
-
mutant E183N, pH 6.0, 30C
14
-
NADPH
-
mutant E183Q, pH 6.0, 30C
34
-
NADPH
-
mutant E183D, pH 6.0, 30C
0.032
-
oxidized dichlorophenolindophenol
-
pH 8.0, 25C
-
0.33
-
ubiquinone-0
-
pH 8.0, 25C
0.015
-
ubiquinone-1
-
pH 8.0, 25C
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
800
-
NADH
-
mutant E183N, pH 6.0, 30C
14331
2000
-
NADH
-
wild-type enzyme, pH 6.0, 30C
14331
2300
-
NADH
-
mutant E183Q, pH 6.0, 30C
14331
6400
-
NADH
-
mutant E183D, pH 6.0, 30C
14331
6500
-
NADH
-
mutant E183H, pH 6.0, 30C
14331
1.8
-
NADPH
-
wild-type enzyme, pH 6.0, 30C
27498
20
-
NADPH
-
mutant E183N, pH 6.0, 30C
27498
90
-
NADPH
-
mutant E183D, pH 6.0, 30C
27498
320
-
NADPH
-
mutant E183Q, pH 6.0, 30C
27498
400
-
NADPH
-
mutant E183H, pH 6.0, 30C
27498
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.015
-
2,6-dichlorophenolindophenol
-
-
0.005
-
5BM-GX
-
-
0.025
-
ADP-ribose
-
pH 8.0, 25C
0.08
-
ADP-ribose
-
pH 8.0, 25C
5.5
-
AMP
-
versus NADH
11.5
-
AMP
-
versus oxidized 2,6-dichlorophenolindophenol
0.001
-
AMS-GX
-
-
0.00022
-
dicoumarol
-
pH 7.5, 30C
0.001
-
molvizarin
-
-
-
0.012
-
NADH
-
in 0.4 M phosphate, using 5,8-dioxy-1,4-naphthoquinone as substrate, at pH 7.0, 25C
0.05
-
NADH
-
pH 7.0, 25C
0.05
-
NADH
-
in 0.4 M phosphate, using ferricyanide as substrate, at pH 7.0, 25C
0.0008
-
otivarin
-
-
0.001
-
piercidin
-
-
0.0003
-
rolliniastatin-1
-
-
0.0006
-
rolliniastatin-2
-
-
1e-06
-
rotenone
-
pH 8.0, 25C, NADH oxidase reaction
2e-05
-
rotenone
-
pH 8.0, 25C, NAD+ reduction
0.00015
-
rotenone
-
pH 8.0, 25C, NADH oxidase reaction
0.0005
-
rotenone
-
pH 8.0, 25C, NADH oxidase reaction
0.004
-
rotenone
-
-
0.0004
-
squamocin
-
-
0.007
-
Triton X-100
-
pH 8.0, 25C, NADH oxidase reaction
0.01
-
Triton X-100
-
pH 8.0, 25C
0.01
-
Triton X-100
-
pH 8.0, 25C, NAD+ reduction
0.025
-
Triton X-100
-
pH 8.0, 25C, NADH oxidase reaction
0.04
-
Triton X-100
-
pH 8.0, 25C, NAD+ reduction
0.05
-
Triton X-100
-
pH 8.0, 25C, NADH oxidase reaction
30
-
vanillylnonanamide
-
mutant enzyme D213E
40
-
vanillylnonanamide
-
wild type enzyme
41
-
vanillylnonanamide
-
mutant enzyme D213N
43
-
vanillylnonanamide
-
mutant enzyme E228D
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00087
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxy-5-propyloctyl]octahydro-2,2'-bifuran-5-yl]-5-propylnonan-1-ol
-
IC50: 870 nM
0.00028
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyethyl]octahydro-2,2'-bifuran-5-yl]undecan-1-ol
-
IC50: 280 nM
3.4e-05
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyheptyl]octahydro-2,2'-bifuran-5-yl]pentadecan-1-ol
-
IC50: 34 nM
3.2e-06
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyheptyl]octahydro-2,2'-bifuran-5-yl]undecan-1-ol
-
IC50: 3.2 nM
7.5e-06
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxynonyl]octahydro-2,2'-bifuran-5-yl]tridecan-1-ol
-
IC50: 7.5 nM
4.5e-05
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxypropyl]octahydro-2,2'-bifuran-5-yl]undecan-1-ol
-
IC50: 45 nM
4.8e-05
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundec-3-yn-1-yl]octahydro-2,2'-bifuran-5-yl]dodec-4-yn-1-ol
-
-
0.0104
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]dodecan-1-ol
-
-
0.000172
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]undeca-3,5,7,9-tetrayn-1-ol
-
IC50: 0.000172 mM
2.7e-05
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-5-ethyl-1-hydroxyoctyl]octahydro-2,2'-bifuran-5-yl]undecan-1-ol
-
IC50: 27 nM
0.0015
-
(1R)-5-ethyl-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxy-5-propyloctyl]octahydro-2,2'-bifuran-5-yl]octan-1-ol
-
IC50: 1500 nM
0.001
-
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diylbis[6-(2-butylphenoxy)hexan-1-ol]
-
IC50: 1000 nM
8.3e-07
-
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diylbis[6-(4-butylphenoxy)hexan-1-ol]
-
IC50: 0.83 nM
0.0045
-
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyldihexan-1-ol
-
IC50: 4500 nM
4.5e-05
-
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyldioctan-1-ol
-
IC50: 45 nM
1.6e-06
-
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyldiundecan-1-ol
-
IC50: 0.0000016 mM
1.6e-06
-
(1R,1'R)-1,1'-(2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyldiundecan-1-ol
-
IC50: 1.6 nM
9e-06
-
(1R,1'S)-1,1'-(2R,5R)-tetrahydrofuran-2,5-diylditridecan-1-ol
-
IC50: 9.0 nM
0.025
-
(1R,1'S)-1,1'-(2R,5R)-tetrahydrofuran-2,5-diylditridecan-1-ol
-
IC50: 0.025 mM
1.2e-06
-
(5S)-3-[(10R)-10-hydroxy-10-[(2R,2'R,5R,5'R)-5'-[(1R)-1 hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]decyl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000012 mM
8.3e-07
-
(5S)-3-[(13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-8-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.00000083 mM
1.7e-06
-
(5S)-3-[(13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]trideca-4,6,8,10-tetrayn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000017 mM
1e-06
-
(5S)-3-[(13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1S)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-10-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.000001 mM
8.5e-07
-
(5S)-3-[(13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1S)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-4-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.00000085 mM
0.00028
-
(5S)-3-[(13R)-13-hydroxy-13-[(2R,5R)-5-[(1S)-1-hydroxytridecyl]tetrahydrofuran-2-yl]trideca-4,6,8,10-tetrayn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.00028 mM
2.3e-06
-
(5S)-3-[(13R)-13-hydroxy-13-[(2R,5R)-5-[(1S)-1-hydroxytridecyl]tetrahydrofuran-2-yl]tridecyl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000023 mM
5.1e-06
-
(5S)-3-[(13S)-13-hydroxy-13-[(2R,5R)-5-[(1S)-1-hydroxytriecyl]tetrahydrofuran-2-yl]tridecyl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000051 mM
1.3e-05
-
(5S)-3-[(16R)-16-hydroxy-16-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]hexadecyl]-5-methylfuran-2(5H)-one
-
IC50: 0.000013 mM
0.000271
-
(5S)-3-[(19R)-19-hydroxy-19-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]nonadecyl]-5-methylfuran-2(5H)-one
-
IC50: 0.000271 mM
1.1e-06
-
(5S)-3-[(2E,13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-2-en-4-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000011 mM
1.4e-05
-
(5S)-3-[(5R)-5-hydroxy-5-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]pentyl]-5-methylfuran-2(5H)-one
-
IC50: 0.000014 mM
5.2e-06
-
(5S)-3-[(7E,13S)-13-hydroxy-13-[(2R,5R)-5-[(1S)-1-hydroxytridecyl]tetrahydrofuran-2-yl]tridec-7-en-9-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000052 mM
9.2e-07
-
(5S)-3-[(8E,13R)-13-hydroxy-13-[(2R,2'R,5R,5'R)-5'-[(1S)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]tridec-8-en-10-yn-1-yl]-5-methylfuran-2(5H)-one
-
IC50: 0.00000092 mM
1.6e-06
-
(5S)-3-[(8R)-8-hydroxy-8-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]octyl]-5-methylfuran-2(5H)-one
-
IC50: 0.0000016 mM
0.057
-
2-(4-butylbenzylamino)-3-methylchromen-4-one
-
-
0.06
-
2-(4-butylbenzyloxy)-3-methylchromen-4-one
-
-
0.0004
-
2-n-decyl-quinazoline-4-yl-amine
-
IC50: 0.0004 mM
0.052
-
2-[(4-butylbenzyl)sulfanyl]-3-methyl-4H-chromen-4-one
-
-
0.133
-
2-[4-(4-fluorobutyl)benzylamino]-3-methylchromen-4-one
-
-
0.033
-
2-[4-(4-fluorobutyl)benzyloxy]-3-methylchromen-4-one
-
-
0.009
-
2-[4-(4-fluorobutyl)benzylsulfanyl]-3-methylchromen-4-one
-
-
1e-05
-
37-methoxyquinoxalinone
-
IC50: 10 nM
1.7e-05
-
39-pyridopyrazinone
-
IC50: 17 nM
0.1
-
5-(N-ethyl)-N-isopropylamiloride
-
IC50 : 0.1 mM
4.5e-06
-
6-amino-4-(4-tert-butylphenethylamino)quinazoline
P17694
pH and temperature not specified in the publication
-
4.5e-06
-
6-amino-4-(4-tert-butylphenethylamino)quinazoline
-
pH and temperature not specified in the publication
-
2.3e-06
-
6-azido-N-[2-(4-tert-butylphenyl)ethyl]-6,7-dihydroquinazolin-4-amine
P17694
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.07
-
benzamil
-
IC50: 0.07 mM
8.3e-07
-
bullatacin
-
IC50: 0.00000083 mM
0.25
-
dicyclohexylcarbodi-imide
-
90% inhibition, IC50: 0.25 mM
0.013
-
diphenylene iodonium
-
75% inhibition, IC50: 0.013 mM
0.09
-
fenazaquin
-
-
0.00017
-
Myxothiazol
-
IC50: 170 nM
0.009
-
palmitate
-
IC50: 0.009 mM, at 25C and pH 8.0
1.3e-06
-
Piericidin A
-
IC50: 0.0000013 mM
0.008
-
pyridaben
-
-
0.002
-
rotenone
-
IC50: 0.002 mM
0.016
-
rotenone
-
-
8.5e-07
-
squamocin M
-
IC50: 0.00000085 mM
0.01
0.05
Zn2+
-
pH-dependent potent inhibitor, IC50: 0.01-0.05 mM at pH 7.5, depending on the enzyme state, Zn2+ does not inhibit NADH oxidation or intramolecular electron transfer, so it probably inhibits either proton transfer to bound quinone or proton translocation.
0.052
-
[2-(4-butyl)benzylsulfanyl]-3-methylchromen-4-one
-
-
0.0017
-
(1R,1'R)-1,1'-((2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyl)-bis-(6-(4-n-butylphenoxy)hex-3-yn-1-ol)
-
-
additional information
-
(1R,1'R)-1,1'-((2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyl)-bis-(6-(4-n-butylphenoxy)hexan-1-ol)
-
IC50: above 15 mM
0.15
-
flutamide
-
-
-
additional information
-
additional information
-
IC50 for polymyxin B is 0.0014 mg/ml, IC50 for nanaomycin A is 0.031 mg/ml
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0098
-
-
mutant enzyme E234Q, using ubiquinone-1 as substrate
0.04
-
-
mutant enzyme E36A, using deamino-NADH as electron donor
0.042
-
-
mutant enzyme E36Q, using deamino-NADH as electron donor
0.08
-
-
mutant enzyme R25A/R26A, using deamino-NADH as electron donor
0.149
-
-
mutant enzyme E72Q, using deamino-NADH as electron donor
0.15
-
-
mutant enzyme E234Q, using hexammineruthenium-(III)-chloride as substrate
0.151
-
-
mutant enzyme R25A, using deamino-NADH as electron donor
0.161
-
-
wild type enzyme, using ubiquinone-1 as substrate
0.163
-
-
mutant enzyme E228Q, using hexammineruthenium-(III)-chloride as substrate
0.175
-
-
mutant enzyme E234D, using ubiquinone-1 as substrate
0.176
-
-
mutant enzyme R25K, using deamino-NADH as electron donor
0.186
-
-
NADH-ubiquinone-0 oxidoreductase activity
0.211
-
-
mutant enzyme R209H, using NADH as substrate
0.213
-
-
mutant enzyme E228K, using hexammineruthenium-(III)-chloride as substrate
0.222
-
-
mutant enzyme R26A, using deamino-NADH as electron donor
0.229
-
-
mutant enzyme R209F, using hexammineruthenium-(III)-chloride as substrate
0.245
-
-
mutant enzyme D213E, using hexammineruthenium-(III)-chloride as substrate
0.249
-
-
mutant enzyme R209H, using hexammineruthenium-(III)-chloride as substrate
0.256
-
-
mutant enzyme R209F, using NADH as substrate
0.259
-
-
mutant enzyme V206E, using hexammineruthenium-(III)-chloride as substrate
0.265
-
-
mutant enzyme R209K, using hexammineruthenium-(III)-chloride as substrate
0.268
-
-
mutant enzyme H210T, using NADH as substrate; mutant enzyme R209K, using NADH as substrate
0.273
-
-
mutant enzyme E72A, using deamino-NADH as electron donor
0.274
-
-
mutant enzyme E228K, using NADH as substrate; mutant enzyme Y229H, using hexammineruthenium-(III)-chloride as substrate
0.305
-
-
mutant enzyme E228D, using hexammineruthenium-(III)-chloride as substrate
0.31
-
-
mutant enzyme H210F, using NADH as substrate
0.313
-
-
mutant enzyme V206E, using NADH as substrate
0.316
-
-
mutant enzyme H210T, using hexammineruthenium-(III)-chloride as substrate
0.32
-
-
mutant enzyme E228Q, using NADH as substrate
0.324
-
-
mutant enzyme D213E, using NADH as substrate
0.329
-
-
mutant enzyme H210F, using hexammineruthenium-(III)-chloride as substrate
0.341
-
-
mutant enzyme D213N, using NADH as substrate
0.348
-
-
mutant enzyme Y229H, using NADH as substrate
0.351
-
-
mutant enzyme G21V, using deamino-NADH as electron donor
0.354
-
-
mutant enzyme E216A, using hexammineruthenium-(III)-chloride as substrate
0.368
-
-
mutant enzyme D213N, using hexammineruthenium-(III)-chloride as substrate
0.424
-
-
mutant enzyme E228D, using NADH as substrate
0.442
-
-
mutant enzyme E216A, using NADH as substrate
0.514
-
-
mutant enzyme F15A, using deamino-NADH as electron donor
0.556
-
-
mutant enzyme R85K, using deamino-NADH as electron donor
0.564
-
-
mutant enzyme R85A, using deamino-NADH as electron donor
0.568
-
-
mutant enzyme R87A, using deamino-NADH as electron donor
0.57
-
-
in 50 mM MOPS containing 10 mM MgCl2 at pH 7.3, using 0.25 mM deamino-NADH as substrate
0.571
-
-
wild type enzyme, using deamino-NADH as electron donor
0.603
-
-
mutant enzyme R87K, using deamino-NADH as electron donor
0.62
-
-
mutant enzyme R26K, using deamino-NADH as electron donor
0.62
-
-
mutant enzyme H129A, using hexamineruthenium(III)-chloride as substrate
0.63
-
-
wild type enzyme, using NADH as substrate
0.8
-
-
wild type enzyme, using hexammineruthenium-(III)-chloride as substrate
0.84
-
-
wild type enzyme, using hexamineruthenium(III)-chloride as substrate
1.144
-
-
wild type enzyme, using hexammineruthenium-(III)-chloride as substrate
1.2
-
-
NADH:duroquinone reductase activity
1.3
-
-
50C, 0.02 mM ubiquinone-2 as substrate
1.34
-
-
mutant enzyme E234D, using hexammineruthenium-(III)-chloride as substrate
2.2
-
-
membrane extract, using hexaammineruthenium-III-chloride as substrate
2.3
-
-
mutant enzyme R141M, NADH-dependent activity of complex 1 containing proteoliposomes using n-decylubiquinone as substrate
3.4
-
-
-
4.1
-
-
in 20 mM MOPS containing 50 mM KCl at pH 7.4, using n-decylubiquinone as substrate
4.8
-
-
in 20 mM MOPS containing 50 mM KCl at pH 7.4, using ubiquinone-1 as substrate
5.5
-
-
wild type enzyme, NADH-dependent activity of complex 1 containing proteoliposomes using n-decylubiquinone as substrate
10.3
-
-
NADH-ferricyanide oxidoreductase activity; reduction of K3Fe(CN)6
11.5
-
-
activity with ubiquinone-2
13.2
-
-
reduction of Coenzyme Q10
16.1
-
-
mutant enzyme R141M, NADH-dependent activity of complex 1 containing proteoliposomes using hexaammineruthenium-(III)-chloride as substrate
23
-
-
wild type enzyme, NADH-dependent activity of complex 1 containing proteoliposomes using hexaammineruthenium-(III)-chloride as substrate
35.91
-
-
ca. 20 h survival after seizures
36.28
-
-
acute phase of seizures
39.1
-
-
in 20 mM MOPS containing 50 mM KCl at pH 7.4, using hexamineruthenium(III)-chloride as substrate
44
-
-
membrane extract
61.9
-
-
reaction with ubiquinone-6
64
-
-
NADH:hexamineruthenium(III)-chloride oxidoreductase activity
90
-
-
after purification, using hexaammineruthenium-III-chloride as substrate
100.6
-
-
controls
102
-
-
controls
195
-
-
NADH + ubiquinone-2, 60C
273
-
-
after 6.2fold purification
1671
-
-
reaction with ubiquinone-2
additional information
-
-
-
additional information
-
-
-
additional information
-
-
NADH/ferricyanide oxidoreductase activity (measured as ferricyanide reduction) and NAD(P)H oxidase activity (measured as oxygen consumption) of cytoplasmic membranes from Escherichia coli recombinantly expressing the enzyme
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.5
9.5
-
reaction with ubiquinone-6 is almost constant between pH 4.5 and pH 9.5
4.5
-
-
reaction with ferricyanide
5
-
-
reduction of NAD+ with reduced methyl viologen
6
7
-
mutant E183H, activity with NADH
6
-
-
assay at
6
-
-
mutant E183H, activity with NADPH; wild-type enzyme, activity with NADH, first peak
6.2
-
-
reaction with ubiquinone-2
6.5
-
-
wild-type enzyme, activity with NADPH
7.1
-
-
reaction with ubiquinone-1
7.4
-
-
assay at
7.4
-
-
assay at
7.5
8.5
-
-
7.5
-
-
reaction with 2,6-dichlorophenolindophenol
7.5
-
-
assay at
7.5
-
-
wild-type enzyme, activity with NADH, second higher peak
7.5
-
-
assay at
7.6
-
-
assay at
8
-
-
assay at
9
-
-
assay at
10
-
-
reaction with ferricyanide or 1,1'-carbamoylmethylviologen
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.5
7
-
50% of maximal activity at pH 3.5 and 7.0, reaction with ferricyanide
5
8
-
activity range
5.5
7.5
-
pH 5.5: about 80% of maximal activity, pH 7.5: about 85% of maximal activity
6
10
-
pH 6.0: about 50% of maximal activity, pH 10.0: about 50% of maximal activity
6
9
-
-
6
9
-
activity range
6.7
7.9
-
about 90% of maximal activity at pH 6.7 and at pH 7.9, reaction with ubiquinone-1
8
10.3
-
pH 8.0: about 60% of maximal activity, pH 10.3: about 30% of maximal activity
additional information
-
-
production of superoxide by complex I during reverse electron transport is at least 3fold more sensitive to the pH gradient than to the membrane potential
additional information
-
-
only NADH binding to the enzyme in pH-dependent. NADH binding to the free enzyme is accelerated by protonation of an amino acid (possibly His)
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
30
-
assay at
25
-
-
assay at
25
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
32
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
35
80
-
activity increases 4fold from 35C to 80C, the maximal possible operating temperature
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.67
-
-
subunit ND 6, calculation from nucleotide sequence
3.84
-
-
subunit ND 6, calculation from nucleotide sequence
4.17
-
-
subunit NDUFAB1, calculation from nucleotide sequence
4.44
-
-
subunit NDUFB2, calculation from nucleotide sequence
4.48
-
-
subunit NDUFB2, calculation from nucleotide sequence
4.5
-
-
subunit ND 3, calculation from nucleotide sequence
4.6
-
-
subunit ESSS, calculation from nucleotide sequence
4.71
-
-
subunit NDUFAB1, calculation from nucleotide sequence
4.92
-
-
subunit NDUFB8, calculation from nucleotide sequence
5.07
-
-
subunit NDUFV2, calculation from nucleotide sequence
5.1
-
-
subunit NDUFA1, calculation from nucleotide sequence
5.1
-
-
subunit NDUFS8, calculation from nucleotide sequence
5.13
-
-
subunit NDUFS8, calculation from nucleotide sequence
5.24
-
-
subunit NDUFS1, calculation from nucleotide sequence
5.26
-
-
subunit NDUFB8, calculation from nucleotide sequence
5.28
-
-
subunit NDUFS1, calculation from nucleotide sequence
5.31
-
-
subunit NDUFV2, calculation from nucleotide sequence
5.43
-
-
subunit ND 4L, calculation from nucleotide sequence
5.45
-
-
subunit NDUFS3, calculation from nucleotide sequence
5.55
-
-
subunit NDUFS3, calculation from nucleotide sequence
5.86
-
-
subunit NDUFS2, calculation from nucleotide sequence
5.95
-
-
subunit NDUFS2, calculation from nucleotide sequence
5.96
-
-
subunit NDUFA10, calculation from nucleotide sequence
6.2
-
-
isoelectric focusing
6.25
-
-
subunit NDUFV3, calculation from nucleotide sequence
6.31
-
-
subunit NDUFB5, calculation from nucleotide sequence
6.39
-
-
subunit NDUFV3, calculation from nucleotide sequence
6.42
-
-
subunit ND 1, calculation from nucleotide sequence; subunit NDUFB5, calculation from nucleotide sequence
6.42
-
-
subunit ND 1, calculation from nucleotide sequence
6.64
-
-
subunit NDUFS6, calculation from nucleotide sequence
6.84
-
-
subunit NDUFA5, calculation from nucleotide sequence
7.53
-
-
subunit NDUFV1, calculation from nucleotide sequence
7.57
-
-
subunit NDUFB10, calculation from nucleotide sequence
7.68
-
-
subunit NDUFB9, calculation from nucleotide sequence
7.82
-
-
subunit NDUFA5, calculation from nucleotide sequence
7.92
-
-
subunit NDUFV1, calculation from nucleotide sequence
7.93
-
-
subunit NDUFS6, calculation from nucleotide sequence
8.03
-
-
subunit NDUFA3, calculation from nucleotide sequence
8.19
-
-
subunit NDUFB10, calculation from nucleotide sequence
8.29
-
-
subunit B14.7, calculation from nucleotide sequence
8.3
-
-
subunit B16.6, calculation from nucleotide sequence
8.3
-
-
subunit B14.7, calculation from nucleotide sequence
8.34
-
-
subunit NDUFC1, calculation from nucleotide sequence
8.35
-
-
subunit NDUFB7, calculation from nucleotide sequence
8.39
-
-
subunit NDUFA8, calculation from nucleotide sequence
8.69
-
-
subunit NDUFB7, calculation from nucleotide sequence
8.76
-
-
subunit NDUFA8, calculation from nucleotide sequence
9
-
-
subunit NDUFA3, calculation from nucleotide sequence
9.01
-
-
subunit NDUFB3, calculation from nucleotide sequence
9.1
-
-
subunit NDUFS5, calculation from nucleotide sequence
9.15
-
-
subunit ND 5, calculation from nucleotide sequence
9.34
-
-
subunit ND 5, calculation from nucleotide sequence
9.38
-
-
subunit NDUFC2, calculation from nucleotide sequence
9.41
-
-
subunit NDUFC2, calculation from nucleotide sequence
9.42
-
-
subunit ND 4, calculation from nucleotide sequence
9.45
-
-
subunit NDUFB1, calculation from nucleotide sequence
9.45
-
-
subunit ND 4, calculation from nucleotide sequence
9.47
-
-
subunit B16.6, calculation from nucleotide sequence
9.48
-
-
subunit NDUFA9, calculation from nucleotide sequence
9.49
-
-
subunit NDUFS4, calculation from nucleotide sequence
9.51
-
-
subunit NDUFA1, calculation from nucleotide sequence
9.52
-
-
subunit B17.2, calculation from nucleotide sequence; subunit NDUFA4, calculation from nucleotide sequence
9.64
-
-
subunit NDUFA9, calculation from nucleotide sequence
9.65
-
-
subunit NDUFS4, calculation from nucleotide sequence
9.71
-
-
subunit NDUFS7, calculation from nucleotide sequence
9.75
-
-
subunit NDUFA2, calculation from nucleotide sequence
9.79
-
-
subunit NDUFB6, calculation from nucleotide sequence
9.82
-
-
subunit ND 2, calculation from nucleotide sequence; subunit NDUFB4, calculation from nucleotide sequence
9.89
-
-
subunit NDUFB4, calculation from nucleotide sequence
9.93
-
-
subunit ND 2, calculation from nucleotide sequence
10.01
-
-
subunit NDUFA2, calculation from nucleotide sequence
10.04
-
-
subunit NDUFB6, calculation from nucleotide sequence
10.1
-
-
subunit NDUFA6, calculation from nucleotide sequence
10.15
-
-
subunit NDUFA6, calculation from nucleotide sequence
10.17
-
-
subunit NDUFA7, calculation from nucleotide sequence
10.3
-
-
subunit B17.2, calculation from nucleotide sequence
10.48
-
-
subunit NDUFA7, calculation from nucleotide sequence
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
in the high positive schizophrenic group a positive correlation exists between cerebral glucose metabolism and complex I activity in the basal ganglia (lentiform nucleus including the putamen and globus pallidus) and the thalamus, but reaches significance only for its left side
Manually annotated by BRENDA team
-
complex I activity is significantly higher in high positive schizophrenics as compared to control subjects and low positive schizophrenic patients. In low positive schizophrenic patients complex I activity does not differ from that of the control group. Entering age and gender as covariates has no effect on the significance of difference in complex I activity between subject groups. Significant positive correlation between complex I activity and the severity of positive symptoms
Manually annotated by BRENDA team
-
NADH dehydrogenase activity in the platelets of patients with Parkinson's disease from an Indian population is lower than that in healthy age and gender-matched controls
Manually annotated by BRENDA team
-
in the low positive schizophrenic group, a region of negative correlation between cerebral glucose metabolism and complex I activity is identified bilaterally in the cerebellum and brainstem
Manually annotated by BRENDA team
-
in the low positive schizophrenic group, a region of negative correlation between cerebral glucose metabolism and complex I activity is identified bilaterally in the cerebellum and brainstem
Manually annotated by BRENDA team
-
severe decrease of complex I activity in a patient with Leigh syndrome and an elevated complex IV/complex I activity ratio
Manually annotated by BRENDA team
-
from mediobasal hypothalamus and midbrain
Manually annotated by BRENDA team
Mus musculus C57/Bl
-
from mediobasal hypothalamus and midbrain
-
Manually annotated by BRENDA team
-
fully assembled complex I is decreased in patient skin fibroblasts
Manually annotated by BRENDA team
-
complex I activity in cultured skin fibroblasts is in the normal range in a patient with Leigh syndrome, but complex IV/complex I activity ratio is significantly elevated and complex I/citrate synthase is decreased
Manually annotated by BRENDA team
-
TGFalpha-transfected mouse hepatocyte cell line
Manually annotated by BRENDA team
-
in the high positive schizophrenic group a positive correlation exists between cerebral glucose metabolism and complex I activity in the basal ganglia (lentiform nucleus including the putamen and globus pallidus) and the thalamus, but reaches significance only for its left side
Manually annotated by BRENDA team
additional information
-
procyclic form of the organism
Manually annotated by BRENDA team
additional information
-
SHSY cell
Manually annotated by BRENDA team
additional information
-
CCL16-B2 cell and V79-G18 cell
Manually annotated by BRENDA team
additional information
-
transmitochondrial cell line, cybrids from a patient with a multisystem mitochondrial disorder with a G6930A nonsense mutation in the COX I gene. G6930A mutation causes a disruption in the assembly and defective activity of complex VI
Manually annotated by BRENDA team
additional information
-
cerebellar granule neuron
Manually annotated by BRENDA team
additional information
-
in the control group, no areas of significant positive or negative correlation between cerebral glucose metabolism and peripheral complex I activity exist
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
electron microscopy reveals the two-part structure of the complex consisting of a peripheral and a membrane arm. The peripheral arm contains all known cofactors and the NADH-binding site, whereas the membrane arm has to be involved in proton translocation
Manually annotated by BRENDA team
-
conserved lysine residues of the membrane subunit NuoM are involved in energy conversion by the proton-pumping NADH:ubiquinone oxidoreductase
Manually annotated by BRENDA team
-
the membrane-bound respiratory enzymes differs from the canonical NADH: dehydrogenase (complex I), because it is not involved in the vectorial transfer of protons across membranes
Manually annotated by BRENDA team
-
subunit NuoA topology modeling, overview
Manually annotated by BRENDA team
Escherichia coli BW25113, Escherichia coli GR19N
-
-
-
Manually annotated by BRENDA team
-
activities of submitochondrial fragments from heart and brain, overview
Manually annotated by BRENDA team
-
alternative NADH dehydrogenase activity is located exclusively at the external face of the mitochondrial inner membrane
Manually annotated by BRENDA team
-
the mitochondrial multienzyme-complex is of dual origin. 6 of the at least 22 subunits with MW of 70000 Da, 48000 Da, 37000 Da, 25000 Da, 22000 Da and 18000 Da are synthesized in mitochondria. 11 subunits are synthesized in the cytoplasm
Manually annotated by BRENDA team
-
constitutively high content; membrane
Manually annotated by BRENDA team
-
inner membrane; loosly bound to inner mitochondrial membrane
Manually annotated by BRENDA team
-
the enzyme oxidizes NADH in the mitochondrial matrix and reduces ubiquinone in the inner mitochondrial membrane
Manually annotated by BRENDA team
-
NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria is a membrane-bound enzyme that contains 45 different subunits
Manually annotated by BRENDA team
-
DE2 faces the intermembrane space
Manually annotated by BRENDA team
-
submitochondrial fragments
Manually annotated by BRENDA team
Caenorhabditis elegans N2, Escherichia coli GV102, Mus musculus C57/Bl, Thermus thermophilus HB-8
-
-
-
Manually annotated by BRENDA team
additional information
-
submitochondrial particles
-
Manually annotated by BRENDA team
additional information
-
extramitochondrial membrane
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
12000
-
-
subunit NdhE
18000
-
-
subunit NdhJ
25000
-
-
SDS-PAGE, NuoE subunit
28000
-
-
subunit NdhK
46000
-
-
subunit NdhH
50000
-
-
gel filtration
50000
-
-
SDS-PAGE
50000
-
-
calculated from sequence of cDNA
51000
-
-
nuo-I subunit of wild type enzyme, SDS-PAGE
51000
-
-
SDS-PAGE
52000
-
-
SDS-PAGE, NuoF subunit
53000
-
-
SDS-PAGE
55000
-
-
SDS-PAGE
60000
-
-
gel filtration
64660
-
-
calculated from amino acid sequence
65000
-
-
gel filtration
69000
-
-
gel filtration
87000
-
-
disc gel electrophoresis
95000
-
-
gel filtration
200000
-
-
non-denaturing PAGE
210000
-
-
gel filtration
250000
-
-
soluble subcomplex
300000
-
-
membrane subcomplex
520000
-
-
above, gel filtration
550000
-
-
sucrose density gradient centrifugation
550000
-
-
whole enzyme consisting of membrane and soluble subcomplex, SDS-PAGE
570000
-
-
about, recombinant His-tagged complex I, gel filtration
600000
-
-
gel filtration
610000
-
-
calculation from sedimentation data
700000
-
-
about, sucrose density gradient centrifugation
900000
-
-
-
950000
-
-
whole wild type enzyme, SDS-PAGE
980000
-
-
-
additional information
-
-
several molecular mass forms of the purified complex exist
additional information
-
-
the enzyme exists in two kinetically and structurally distinct slowly interconvertible forms, active form A and de-activated form D. Continous slow cycling between form A and form D occurs during the steady-state operation of complex I in the mitochondria
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 57000, SDS-PAGE
?
-
x * 53000, SDS-PAGE
?
-
x * 37000, SDS-PAGE
?
-
x * 55000, SDS-PAGE
?
-
x * 8139 (subunit NDUFA1) + x * 10916 (subunit NDUFA2) + x * 9331 (subunit NDUFA3) + x * 9327 (subunit NDUFA4) + x * 13360 (subunit NDUFA5) + x * 15283 (subunit NDUFA6) + x * 12576 (subunit NDUFA7) + x * 19992 (subunit NDUFA8) + x * 38810 (subunit NDUFA9) + x * 36947 (subunit NDUFA10) + x * 10130 (subunit NDUFAB1) + x * 6996 (subunit NDUFB1) + x * 8491 (subunit NDUFB2) + x * 11690 (subunit NDUFB3) + x * 15081 (subunit NDUFB4) + x * 16858 (subunit NDUFB5) + x * 15515 (subunit NDUFB6) + x * 16331 (subunit NDUFB7) + x * 18816 (subunit NDUFB8) + x * 21984 (subunit NDUFB9) + x * 21024 (subunit NDUFB10) + x * 5753 (subunit NDUFC1) + x * 14322 (subunit NDUFC2) + x * 77183 (subunit NDUFS1) + x * 49230 (subunit NDUFS2) + x * 26479 (subunit NDUFS3) + x * 15356 (subunit NDUFS4) + x * 12648 (subunit NDUFS5) + x * 10777 (subunit NDUFS6) + x * 20280 (subunit NDUFS7) + x * 20442 (subunit NDUFS8) + x * 48626 (subunit NDUFV1) + x * 23847 (subunit NDUFV2) + x * 8028 (subunit NDUFV3) + x * 35651 (subunit ND 1) + x * 38764 (subunit ND 2) + x * 13091 (subunit ND3) + x * 51881 (subunit ND 4) + x * 68375 (subunit ND 5) + x * 18626 (subunit ND 6) + x * 10493 (subunit ND 4L) + x * 16860 (subunit B16.6) + x * 15115 (subunit B14.7) + x * 17374 (subunit B17.2) + x * 14343 (subunit ESSS), calculation from nucleotide sequence
?
-
x * 8148 (subunit NDUFA1) + x * 10845 (subunit NDUFA2) + x * 11482 (subunit NDUFA3) + x * 13412 (subunit NDUFA5) + x * 15224 (subunit NDUFA6) + x * 12500 (subunit NDUFA7) + x * 21966 (subunit NDUFA8) + x * 38872 (subunit NDUFA9) + x * 36843 (subunit NDUFA10) + x * 10124 (subunit NDUFAB1) + x * 8454 (subunit NDUFB2) + x * 11267 (subunit NDUFB3) + x * 15064 (subunit NDUFB4) + x * 16870 (subunit NDUFB5) + x * 15638 (subunit NDUFB6) + x * 16568 (subunit NDUFB7) + x * 18851 (subunit NDUFB8) + x * 21396 (subunit NDUFB9) + x * 20859 (subunit NDUFB10) + x * 14359 (subunit NDUFC2) + x * 76860 (subunit NDUFS1) + x * 49244 (subunit NDUFS2) + x * 26452 (subunit NDUFS3) + x * 15215 (subunit NDUFS4) + x * 12700 (subunit NDUFS5) + x * 10598 (subunit NDUFS6) + x * 20248 (subunit NDUFS7) + x * 20406 (subunit NDUFS8) + x * 48583 (subunit NDUFV1) + x * 23933 (subunit NDUFV2) + x * 8238 (subunit NDUFV3) + x * 36133 (subunit ND 1) + x * 38653 (subunit ND 2) + x * 13071 (subunit ND3) + x * 51783 (subunit ND 4) + x * 68618 (subunit ND 5) + x * 18923 (subunit ND 6) + x * 10659 (subunit ND 4L) + x * 16777 (subunit B16.6) + x * 14854 (subunit B14.7) + x * 17334 (subunit B17.2) + x * 14384 (subunit ESSS), calculation from nucleotide sequence
?
-
the bacterial complex consists of 14 different subunits, deletion of any of the nuo-genes results in a loss of complex I activity in the membrane
dimer
-
2 * 33000, SDS-PAGE
dimer
-
2 * 50000, SDS-PAGE
dimer
-
2 * 24000, SDS-PAGE
dodecamer
-
12 * 17000, SDS-PAGE
dodecamer
-
-
monomer
-
1 * 47000, SDS-PAGE
monomer
-
1 * 36000, SDS-PAGE
monomer
-
1 * 50000, SDS-PAGE
monomer
-
1 * 550000, SDS-PAGE
tetradecamer
-
-
tetradecamer
-
-
tridecamer
-
-
tridecamer
-
subunits NuoA through NuoN
tridecamer
Escherichia coli ANN023
-
-
-
monomer
-
1 * 46000, SDS-PAGE
additional information
-
the enzyme complex is composed of at least 10 polypeptides ranging in MW from 10000 Da to 70000 Da
additional information
-
the NADH:ubiquinone oxidoreductase complex is composed of three distinct fragments: 1. IP: a water soluble Fe-S-protein that is composed of 5-6 polypeptides and contains four Fe-S clusters, 2. FP: a water-soluble FeS-flavoprotein that is composed of three polypeptides and contains FMN and two FeS clusters, 3. a water-insoluble fraction containing phospholipids and hydrophobic polypeptides
additional information
-
the enzyme contains 13 different subunits
additional information
-
isolated complex contains 14 major polypeptides
additional information
-
at least five major polypeptides with MW of 76000 Da, 46000 Da, 39000 Da, 33000 Da and 27000 Da
additional information
-
consists of about 25 different subunits
additional information
-
the enzyme complex consists of at least 43 proteins, seven are encoded by the mitochondrial genome, while the remainder are encoded by the nuclear genome
additional information
-
composed of at least 32 individual subunits
additional information
-
about 15 polypeptides including that at 80000 Da, 54000 Da, 53000 Da, 51000 Da, 27000 Da, 25000 Da and 22000 Da cross react with polyclonal antibodies raised against complex I from Neurospora crassa
additional information
-
four polypeptides, of 15000 Da, 20000 Da, 38000 Da and 51000 Da are identified as subunits of complex I by SDS-PAGE
additional information
-
the enzyme complex comprises more than 35 subunits, the majority of which are encoded by the nucleus. Only five components ND1, ND2, ND4, ND5, and ND6 are coded for by the mitochondrial genome. Dum 5 mutant has a 1T deletion in the 3'UTR of nd5 whereas dum 17 is a 1T deletion in the coding sequence of nd6. Absence of intact ND1 or ND6 subunits prevents the assembly of the 850000 Da whole complex. Loss of ND4 or ND4/ND5 leads to the formation of a subcomplex of 650000 Da
additional information
-
proton-translocating NADH-quinone oxidoreductase is composed of at least 14 dissimilar subunits, designated NQO1-14. NQO1, NQO2, NQO3, NQO9, and probably NQO6 subunits are cofactor binding subunits
additional information
-
the NQO6 subunits plays a key role in electron transfer by functionally coupling iron-sulfur cluster N2 to quinone
additional information
-
enzyme is composed of at least 14 subunits
additional information
-
enzyme complex contains approximately 25 unlike polypeptides in three distinct fragments: 1. HP: contains the bulk of phospholipids of the complex I. 2. IP: contains polypeptides of 75000 Da, 49000 Da, 30000 Da, 18000 Da, 15000 Da and 13000 Da, 3. FP: contains polypeptides of 9000 Da, 24000 Da, and 51000 Da. FP and IP are surrounded by HP polypeptides
additional information
-
-
additional information
-
-
additional information
-
enzyme complex is composed of approximately 10 unlike polypeptides, the NADH-binding subunit has a MW of 47000 Da determined by SDS-PAGE
additional information
-
may contain up to 14 subunits
additional information
-
consists of 45 different subunits
additional information
-
NuoK is the smallest subunit of Escherichia coli NDH-1
additional information
-
consists of 30 subunits
additional information
-
consists of 46 subunits
additional information
-
consists of 30 subunits
additional information
-
consists of 45 subunits
additional information
-
consists of 35 subunits
additional information
-
consists of 37 subunits
additional information
-
two domains, hydrophilic and hydrophobic, constitute Complex I. The hydrophilic domain of Complex I contains noncovalently bound FMN and 8-9 FeS clusters, 8 of which are organized as a continuous eT chain connecting FMN and a UQ binding site. One or two UQ-binding sites are located at the interface between the hydrophilic and membrane Complex I domains or in the membrane domain close to the interface area. The hydrophilic domain is composed of 6 or 7 core subunits and protrudes to cytoplasm or mitochondrial matrix. The substrate binding site is located in the open cleft on the surface of the protein. The conserved residues aligning this solvent-accessible cavity form an unusual Rossmann fold, which provides tight packing of the substrate, ensures the planar condensed system of the nicotinamide and the FMN isoalloxazine rings and therefore determines high affinity to NADH, substrate specificity and high rate of hydride transfer to FMN. The membrane domain of bacterial Complex I consists of 7 subunits equivalent to core subunits of mitochondrial enzyme
additional information
-
two domains, hydrophilic and hydrophobic, constitute Complex I. The hydrophilic domain of Complex I contains noncovalently bound FMN and 8-9 FeS clusters, 8 of which are organized as a continuous eT chain connecting FMN and a UQ binding site. One or two UQ-binding sites are located at the interface between the hydrophilic and membrane Complex I domains or in the membrane domain close to the interface area. The hydrophilic domain is composed of 6 or 7 core subunits and protrudes to cytoplasm or mitochondrial matrix. The substrate binding site is located in the open cleft on the surface of the protein. The conserved residues aligning this solvent-accessible cavity form an unusual Rossmann fold, which provides tight packing of the substrate, ensures the planar condensed system of the nicotinamide and the FMN isoalloxazine rings and therefore determines high affinity to NADH, substrate specificity and high rate of hydride transfer to FMN
additional information
-
the enzyme nucleotide-binding site is made up of a unique Rossmann fold to accommodate the binding of the substrate NADH and of the primary electron acceptor flavin mononucleotide
additional information
-
complex I consists of 13 different subunits named NuoA-Nand encoded by the nuo operon
additional information
Q9LK88
overall 47 distinct types of proteins were found to form part of Arabidopsis complex I. An additional subunit, ND4L, is present but could not be detected by the procedures employed due to its extreme biochemical properties. Seven of the 48 subunits occur in pairs of isoforms, six of which are experimentally proven. Fifteen subunits of complex I from Arabidopsis are specific for plants
additional information
Thermus thermophilus HB-8
-
the NQO6 subunits plays a key role in electron transfer by functionally coupling iron-sulfur cluster N2 to quinone
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
lipoprotein
-
the enzyme complex contains 0.22 mg of lipid per 650000 Da enzyme
lipoprotein
-
the NADH:ubiquinone oxidoreductase complex is composed of three distinct fragments: 1. IP: a water soluble Fe-S-protein that is composed of 5-6 polypeptides and contains four Fe-S clusters, 2. FP: a water-soluble FeS-flavoprotein that is composed of three polypeptides and contains FMN and two FeS clusters, 3. a water-insoluble fraction containing phospholipids and hydrophobic polypeptides
lipoprotein
-
the enzyme complex contains phospholipids
lipoprotein
-
native lipids play an important role in the activation, stabilization and, as a sonsequence, crystallization of purified complex I
lipoprotein
-
the phospholipid content varies between 26 and 66 mol phosphate per mol of complex in different batches. Complex 1 purified by affinity chromatography can be fully reactivated by returning phosphatidylcholine, phosphatidylethanolamine and cardiolipin, the phospholipids removed by the purification procedure
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
sitting drop vapour diffusion method
-
two different two-dimensionmal crystal forms with p2 and p3 symmetry, are obtained using lipid containing native Escherichia coli extract
-
membrane crystals of the enzyme complex are prepared by adding mixed phospholipid-Triton X-100 micelles and then removing the Triton by dialysis
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
-
-
25C, stable for at least 1 h
4.5
9.5
-
stable
4.5
-
-
activity is irreversibly destroyed below
4.5
-
-
1 h, stable
7
-
-
100C, 15 min, 30% loss of activity
8
-
-
NDH-2 activity increases rapidly at pH 8.0 or above
9
-
-
1 h, about 50% loss of activity
9.5
-
-
activity is irreversibly destroyed above
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
pH 4, stable for at least 1 h
62
-
-
irreversibly inactictivated after 1 minute
65
-
-
3 h, Fe-S cluster remains intact
80
-
-
half-life: 10 h
100
-
-
pH 7, 15 min, 30% loss of activity
additional information
-
-
Triton X-100 partially protects complex I against thermally induced deactivation and partially activates the thermally deactivated enzyme
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, complex I is intact for about 2 days, stable for 3-5 days with inclusion of 10 mM CaCl2
-
not stable to repeated freeze-thaw cycles
-
ORGANIC SOLVENT
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Triton X-100
-
leads to immediate loss of activity
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
storage of 0.3 mg purified enzyme in 2 ml 0.1 M Tris/HCl, pH 8.0, for 24 h at 4C, results in 15% inactivation under anaerobic conditions, 55% inactivation in presence of air
-
392724
the tetranuclear cluster in the isolated NQO3 subunit is sensitive towards oxidants and converts into [3Fe-4S] form
-
392705
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, 8-10 mg protein/ml, stable for at least 1 year
-
-80C, stable for 6 months or longer
-
4C, complex I is intact for about 2 days, stable for 3-5 days with inclusion of 10 mM CaCl2
-
-15C, 0.07 mg/ml enzyme, 0.1 M Tris/HCl, pH 8.0, 72 h, under anaerobic conditions, 70% loss of activity
-
4C, 0.07 mg/ml enzyme, 0.1 M Tris/HCl, pH 8.0, 72 h, under anaerobic conditions, 75% loss of activity
-
in liquid nitrogen, 5% loss of activity after 72 h
-
-80C, alkaline buffer with 40% (w/v) glycerol, one month, without loss of activity
-
-80C, stable for at least 6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
HiLoad column chromatography, DEAE Sepharose fast flow column chromatography, Superdex S-200 gel filtration and Q-Sepharose column chromatography
-
nickel-affinity chromatography
-
enzymically active subcomplexes Ilambda, IS, and IlambdaS
-
Q-Sepharose HP column chromatography and Superose 6 10/300 GL gel filtration
-
Sephacryl S-300 gel-filtration
-
Sephadex G-25 gel filtration
-
DEAE Toyopearl gel filtration and Heparin-Sepharose column chromatography
-
by ion-exchange chromatography and gel filtration
-
DEAE-Trisacryl M anion exchange column chromatography, Source 15Q column chromatography and ultracentrifugation
-
nickel chelation affinity column chromatography
-
partial purification of the NuoCDEFG subcomplex
-
recombinant His-tagged complex I by nickel affinity chromatography and gel filtration
-
recombinant membrane-spanning subunit NuoA of complex I from Escherichia coli strain JM109 as full-length and truncated NuoA C-terminally fused to His-tagged cytochrome c domain by solubilization, ultracentrifugation, and affinity chromatography
-
recombinant wild-type and mutant enzymes from Escherichia coli
-
Source 15Q column chromatography and Sephacryl S-300 gel filtration
-
Strep-Tactin Sepharose column chromatography
-
using column chromatography on DEAE-Sephacel and DEAE-5PW
-
immunocapture-purified
-
ultracentrifugation
-
recombinant NQO3 subunit
-
recombinant His-tagged pfNDH2
-
efficient large scale purification of His-tagged proton translocating complex
-
Ni2+-affinity chromatography and gel filtration
-
Sepharose Fast Flow column chromatography
-
TSKgel 4000SW gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli
-
expression of recombinant enzyme subunits in Escherichia coli, quantitative expression analysis
-
constitutive expression of the tagged wild type, or mutant MWFE or ESSS proteins via a pTRIDENT-neo (tricistronic) vector with the EF1alpha promoter
-
expressed in Escherichia coli
-
expression of His-tagged complex I
-
expression of wild-type and mutant enzymes in Escherichia coli
-
gene nuoA, encoding a membrane-spanning subunit of complex I, expression in Escherichia coli strain Rosetta Gami and Jm109,expression as full-length and truncated NuoA C-terminally fused to His-tagged cytochrome c domain
-
overexpression of the NuoE subunit from complex I
-
expressed in Mycobacterium smegmatis
-
expression in Escherichia coli
-
expression of the subunits NQO4, NQO5 and NQO6 in Escherichia coli
-
NQO3 subunit overexpressed in NQO3
-
expression of His-tagged NDH2 in Escherichia coli
-
the enzyme overexpressed in Escherichia coli acts as a member of the respiratory chain in the host cell
-
the NDI1 gene encoding the rotenone-insensitive internal NADH-quinone oxidoreductase is cotransfected into complex-I-deficient Chinese hamster CCL16-B2 cells. The enzyme is expressed functionally and catalyzes electron transfer from NADH in the matrix to ubiquinone 10 in the inner mitochonbdrial membranes
-
NQO2 subunit expressed in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the gene encoding the alternative NADH dehydrogenases NDE2 is drastically down-regulated from early to late exponential growth, its transcript is severely reduced and/or absent in late exponential phase
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A352V
-
mutation in the 51 kDa subunit, shows mildly decreased NADH-dependent respiration and lactic acidosis
A443F
-
mutation in the 51 kDa subunit, shows decreased NADH-dependent respiration and lactic acidosis
T434M
-
mutation in the 51 kDa subunit, shows decreased NADH-dependent respiration and lactic acidosis
L158P
Chlamydomonas sp.
-
site-directed mutagenesis, introducetion of a Leu157Pro substitution into the Chlamydomonas ND4 subunit of complex I in two recipient strains by biolistic transformation
S2A
-
mutant of phosphorylated subunit ESSS, shows lower levels of mature protein and a significantly reduced complex I activity
S2A/S8A
-
double mutant of phosphorylated subunit ESSS, mutant protein causes a complete failure to assemble
S2E
-
mutant of phosphorylated subunit ESSS, shows lower levels of mature protein and a significantly reduced complex I activity
S30A
-
mutant of phosphorylated subunit ESSS, shows lower levels of mature protein and a significantly reduced complex I activity
S30E
-
mutant of phosphorylated subunit ESSS, shows lower levels of mature protein and a significantly reduced complex I activity
S55A
-
mutant of phosphorylated subunit MWFE, functional complex I can be assembled, mutant protein is expressed at a lower level compared to the wild-type protein
S55D
-
mutant of phosphorylated subunit MWFE, assembly of complex I is completely blocked
S55E
-
mutant of phosphorylated subunit MWFE, assembly of complex I is completely blocked
S55Q
-
mutant of phosphorylated subunit MWFE, assembly of complex I is completely blocked
S8A
-
mutant of phosphorylated subunit ESSS, shows lower levels of mature protein and a significantly reduced complex I activity
S8E
-
mutant of phosphorylated subunit ESSS, shows lower levels of mature protein and a significantly reduced complex I activity
T21A
-
mutant of phosphorylated subunit ESSS, shows lower levels of mature protein and a significantly reduced complex I activity
T21E
-
mutant of phosphorylated subunit ESSS, shows lower levels of mature protein and a significantly reduced complex I activity
D115N
-
45% of deamino-NADH oxidase activity of the wild type enzyme
D146N
-
59% of deamino-NADH oxidase activity of the wild type enzyme, one fourth reduced complex 1 content
D152N
-
59% of deamino-NADH oxidase activity of the wild type enzyme, one third reduced complex 1 content
D213E
-
reduced activity
D213N
-
reduced activity
D77E
-
54% of deamino-NADH oxidase activity of the wild type enzyme
D77N
-
completely abolished electron transfer activity, 12% of deamino-NADH oxidase activity of the wild type enzyme
D94E
-
83% of deamino-NADH oxidase activity of the wild type enzyme
D94N
-
completely abolished electron transfer activity, 12% of deamino-NADH oxidase activity of the wild type enzyme
E119Q
-
88% of deamino-NADH oxidase activity of the wild type enzyme
E144A
-
mutation in subunit NuoM, quinone reductase activity is lost
E144D
-
mutation in subunit NuoM, mutant has wild type sensitivity to rolliniastatin and complete proton-pumping efficiency of complex I; mutation in subunit NuoM, quinone reductase activity is unchanged
E163Q
-
76% of deamino-NADH oxidase activity of the wild type enzyme, one third reduced complex 1 content
E183D
-
site-directed mutagenesis, the mutant shows a 2fold increase in NADH/ferricyanide oxidoreductase activity and a 5fold increase in NADPHoxidase activity compared to the wild-type enzyme
E183H
-
site-directed mutagenesis, the mutant shows a 2fold increase in NADH/ferricyanide oxidoreductase activity and a 2fold increase in NADPHoxidase activitycompared to the wild-type enzyme
E183N
-
site-directed mutagenesis, the mutant shows a 2fold increase in NADH/ferricyanide oxidoreductase activity and a 2fold increase in NADPHoxidase activitycompared to the wild-type enzyme
E183Q
-
site-directed mutagenesis, the mutant shows a similar NADH/ferricyanide oxidoreductase activity and a 2fold increase NADPHoxidase activity compared to the wild-type enzyme
E214K
-
inactive mutant
E216A
-
reduced activity
E228D
-
reduced activity
E228K
-
reduced activity
E228Q
-
reduced activity
E36A
-
almost no NDH-1 activity
E36Q
-
almost no NDH-1 activity
E67D
-
78% of deamino-NADH oxidase activity of the wild type enzyme
E67Q
-
completely abolished electron transfer activity, one fourth reduced complex 1 content, 10% of deamino-NADH oxidase activity of the wild type enzyme
E72A
-
NDH-1 activity similar to wild type enzyme
E72Q
-
NDH-1 activity similar to wild type enzyme
F15A
-
NDH-1 activity similar to wild type enzyme
G21V
-
reduced NDH-1 activity
H101A
-
the NADH dehydrogenase subcomplex (NuoEFG subcomplex) in the cluster N5 mutant is unstable and dissociates from complex I. Recovery of these mutant NuoCDEFG subcomplexes by expressing the His-tagged NuoCD subunit, which has a high affinity to NuoG. At temperatures around -270C no cluster N5 signals are found in the cluster N5 mutant
H101A/C114A
-
the NADH dehydrogenase subcomplex (NuoEFG subcomplex) in the cluster N5 mutant is unstable and dissociates from complex I. Recovery of these mutant NuoCDEFG subcomplexes by expressing the His-tagged NuoCD subunit, which has a high affinity to NuoG. At temperatures around -270C no cluster N5 signals are found in the cluster N5 mutant
H101C
-
the NADH dehydrogenase subcomplex (NuoEFG subcomplex) in the cluster N5 mutant is unstable and dissociates from complex I. Recovery of these mutant NuoCDEFG subcomplexes by expressing the His-tagged NuoCD subunit, which has a high affinity to NuoG. At temperatures around -270C no cluster N5 signals are found in the cluster N5 mutant
H210F
-
reduced activity
H210T
-
reduced activity
K234A
-
mutation in subunit NuoM, quinone reductase activity is lost
K234R
-
mutation in subunit NuoM, quinone reductase activity is lost
R209F
-
reduced activity
R209H
-
reduced activity
R209K
-
reduced activity
R25A
-
reduced NDH-1 activity
R25A/R26A
-
strongly reduced NDH-1 activity
R25K
-
reduced NDH-1 activity
R26A
-
reduced NDH-1 activity
R26K
-
NDH-1 activity similar to wild type enzyme
R85A
-
NDH-1 activity similar to wild type enzyme
R85K
-
NDH-1 activity similar to wild type enzyme
R87A
-
NDH-1 activity similar to wild type enzyme
R87K
-
NDH-1 activity similar to wild type enzyme
V206E
-
reduced activity
W221A
-
mutant is used as a control subcomplex carrying wild-type clusters. At temperatures around -270C a cluster N5 signals is detected in the control
W243A
-
mutation in subunit NuoM, mutant has wild type sensitivity to rolliniastatin and complete proton-pumping efficiency of complex I; mutation in subunit NuoM, quinone reductase activity is decreased
Y229H
-
30% lower activity than wild type enzyme
D146N
Escherichia coli ANN023
-
59% of deamino-NADH oxidase activity of the wild type enzyme, one fourth reduced complex 1 content
-
D152N
Escherichia coli ANN023
-
59% of deamino-NADH oxidase activity of the wild type enzyme, one third reduced complex 1 content
-
D77N
Escherichia coli ANN023
-
completely abolished electron transfer activity, 12% of deamino-NADH oxidase activity of the wild type enzyme
-
E163Q
Escherichia coli ANN023
-
76% of deamino-NADH oxidase activity of the wild type enzyme, one third reduced complex 1 content
-
E214K
Escherichia coli GV102
-
inactive mutant
-
E216A
Escherichia coli GV102
-
reduced activity
-
H210F
Escherichia coli GV102
-
reduced activity
-
V206E
Escherichia coli GV102
-
reduced activity
-
E234D
-
mutant with slightly reduced activity compared to the wild type enzyme
E234Q
-
mutant with strongly reduced activity compared to the wild type enzyme
E107A
-
mutation in the 49000 Da subunit, no effect on complex I contant, mutant enzyme displays no deamino-nicotinamide-adeninedinucleotide:N-decylubiquinone activity
F87L
-
mutation in the 49000 Da subunit, no effect on complex I content, deamino-nicotinamide-adeninedinucleotide:N-decylubiquinone activity is reduced to aboput 60% of the parental strain value. The KM-value for n-decylubiquinone and the I50 value for rotenone are noemal
H129A
-
fully assembled but destabilized enzyme, without deamino-NADH:ubiquinone oxidoreductase activity
P232Q
-
mutation in thge 49000 Da subunit. Complex I assembly is severly impaired in this mutant. Deamino-nicotinamide-adeninedinucleotide:N-decylubiquinone activity is less than 20% of the normal value
R141M
-
reduced activity compared to wild type enzyme
R199W
-
mutation in the 30000 Da subunit, no significant alterations in complex I content or activity can be abserved in isolated mitochondrial membranes
R231E
-
mutation in the 49000 Da subunit of the complex, mutation has no effect on complex I content. Its deamino-nicotinamide-adeninedinucleotide:N-decylubiquinone activity is slightly reduced and its Km-value is somewhat elevated
R231Q
-
mutation in the 49000 Da subunit of the complex, no difference to wild-type enzyme in activity and stability
S416A
-
mutation in the 49000 Da subunit of the complex, mutation has no effect on complex I content. Its deamino-nicotinamide-adeninedinucleotide:N-decylubiquinone activity is slightly reduced. KM-value and I50 value for rotenone are both significantly higher than in the parental strain
S416P
-
mutation in the 49000 Da subunit of the complex, no difference to wild-type enzyme in activity and stability
T157I
-
mutation in the 30000 Da subunit, no significant alterations in complex I content or activity can be abserved in isolated mitochondrial membranes
additional information
-
construction of mrpA or mrpD deletion mutant strains, the deletion strains can be complemented in trans by their respective Mrp protein, but expression of MrpA in the Bacillus subtilis DELTAmrpD strain and vice versa does not improve growth at pH 7.4, mutant strains growth phenotypes, overview
K265A
-
mutation in subunit NuoM, mutant has wild type sensitivity to rolliniastatin and complete proton-pumping efficiency of complex I; mutation in subunit NuoM, quinone reductase activity is decreased
additional information
-
deletion of the nuoN gene results in complete loss of activity
additional information
-
deletion of any of the nuo-genes results in a loss of complex I activity in the membrane, the assembly of subunits is examined
additional information
-
cluster N5 knock-out (DELTAN5) mutant: the NADH dehydrogenase subcomplex (NuoEFG subcomplex) in the cluster N5 mutant is unstable and dissociates from complex I. The data confirm that, cluster N5 has a unique coordination with His(Cys)3 ligands in subunit NuoG. Recovery of these mutant NuoCDEFG subcomplexes by expressing the His-tagged NuoCD subunit, which has a high affinity to NuoG. At temperatures around -270C no cluster N5 signals are found in the cluster N5 mutant
additional information
-
construction of NuoL variants Y544Stop and W592Stop, that contain a stop codon leading to truncations in themiddle and at the end of the horizontal helix. The W592Stop variant is missing the C-terminal TM helix and the Y544Stop variant is missing this helix and approximately half of the amphipathic helix. Proton translocation by the mutant W592Stop variant and the Y544Stop variant after reconstitution in proteoliposomes, overview
additional information
-
construction of several variants with mutations at position 183 exhibiting up to 200fold enhanced catalytic efficiency with NADPH
E67Q
Escherichia coli ANN023
-
completely abolished electron transfer activity, one fourth reduced complex 1 content, 10% of deamino-NADH oxidase activity of the wild type enzyme
-
additional information
-
construction of NuoL variants Y544Stop and W592Stop, that contain a stop codon leading to truncations in themiddle and at the end of the horizontal helix. The W592Stop variant is missing the C-terminal TM helix and the Y544Stop variant is missing this helix and approximately half of the amphipathic helix. Proton translocation by the mutant W592Stop variant and the Y544Stop variant after reconstitution in proteoliposomes, overview
-
Y229H
Escherichia coli GV102
-
30% lower activity than wild type enzyme
-
additional information
-
mutation in the first intron of the NDUFS7 gene (c.17-1167 C > G), creates a strong donor splice site resulting in the generation of a cryptic exon, shows marked decrease of fully assembled complex I
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
gene therapy approaches involving Ndi1p may offer substantial clinical benefits in cases of complex I deficiency
drug development
-
nucleoside analog reverse transcriptase inhibitors are capable of affecting complex I activity in a non-polymerase-gamma/mtDNA mediated pathway. Elevations in superoxide produced at complex I caused by nucleoside analog reverse transcriptase inhibitors can provide a mechanism for the oxidative stress observed with these drugs
medicine
-
a deficient activity of the NADH:ubiquinone oxidoreductase enzyme complex is frequently observed in clinical heterogeneous group of mitochondrial disorders with Leigh (-like) disease as the main contributor. Enzyme complex activity measurement in skeletal muscle is the mainstay of the diagnostic process. Fibroblast studies are a prerequisite whenever prenatal enzyme diagnostic is considered
medicine
-
superoxide production is increased in children with inherited complex I deficiency, which is primarily a consequence of the reduction in cellular complex I activity and not of a further leakage of electrons from mutationally malformed complexes
medicine
-
complex I deficient patients show a specific increase in superoxide dismutase activity. Reactive oxygen species production remains significantly elevated in complex I deficient patients compared to controls, whereas glutathione peroxidase, catalase and glutathione-S-transferase are significantly reduced. Information on the status of reactive oxygen species and marking the alteration of reactive oxygen species scavenging enzymes in peripheral lymphocytes or lymphoblast cell lines will provide a better way to design antioxidant therapies for such disorders like complex I deficiency
medicine
-
identification of a NDUFS7 mutation in a consanguineous family with Leigh syndrome and isolated complex I deficiency
medicine
-
a systemic defect in complex I activity is not present in early Huntington's disease when striatal neuronal degeneration is already present
medicine
-
correlation between peripheral complex I activity and cerebral glucose metabolism in regions implicated in schizophrenia, may be a pathological factor that is differentially expressed in subgroups of schizophrenic patients
medicine
-
cellular levels of reactive oxygen species are significantly increased in cells of patients with nDNA-inherited isolated complex I deficiency. This increase is associated with variable decreases in the amount and intrinsic catalytic activity of complex I. Chronic treatment with a vitamin E derivative (Trolox) increases the amount of complex I and might provide an experimental basis for the use of antioxidants to treat complex I deficient patients
medicine
-
cellular levels of reactive oxygen species are significantly increased in cells of patients with DNA-inherited isolated complex I deficiency. This increase is associated with variable decreases in the amount and intrinsic catalytic activity of complex I. Chronic treatment with a vitamin E derivative (Trolox) increases the amount of complex I and might provide an experimental basis for the use of antioxidants to treat complex I deficient patients
medicine
-
mutations in NADH dehydrogenase ND subunits of complex I are an important genetic cause of childhood mitochondrial encephalopathies
drug development
-
carvedilol exerts its protective antioxidant action both by a direct antioxidant effect and by a preconditioning-like mechanism, via inhibition of mitochondrial complex I
medicine
-
the doxorubicin-inhibited NADH-quinone-reductase may provide a target for the anthracycline antitumor agents
medicine
-
inhibition of complex I may elicit enhanced formation of reactive oxygen species and contribute thus to neuronal injury
medicine
-
radiolabeled MC-I inhibitors as potential myocardial perfusion imaging agents
medicine
-
partial inhibition of mitochondrial respiratory complex I by rotenone reproduces aspects of Parkinsons disease in rodents. Cell vulnerability in the rotenone model of partial complex I deficiency is primarily determined by spare respiratory capacity rather than oxidative stress
medicine
-
the NDI1 gene provides a potentially useful tool for gene therapy of mitochondrial diseases caused by complex I deficiency
medicine
Caenorhabditis elegans N2
-
gene therapy approaches involving Ndi1p may offer substantial clinical benefits in cases of complex I deficiency
-
additional information
-
if phosphorylation occurs in vivo, effects on complex I activity are significant
degradation
-
quantification of superoxide production from Escherichia coli complex I is very prone to artifacts
additional information
-
missense mutation in the MT-ND5 subunit of NADH dehydrogenase in Tibet chicken breed. Significant differences between animals carrying mitochondria with the EF493865.1:m.1627A versus EF493865.1:m.1627C alleles for respiratory control ratio and enzyme activity. MT-ND5 gene variation is significantly associated with brain mitochondrial respiratory function in Tibet chicken embryos under hypoxia, which identifies MT-ND5 as a candidate gene for adaptation to hypoxia (or high hatchability under hypoxia) in Tibet chickens
medicine
-
NADH dehydrogenase activity in the platelets of patients with Parkinson's disease from an Indian population is lower than that in healthy age and gender-matched controls. The study contribute to the evidence of mitochondrial dysfunction playing a major role in the disease mechanism of Parkinson's disease and opens avenues for therapeutic intervention
additional information
-
crucial role for mitochondrial nitric oxide synthase in oxidative stress caused by mitochondrial complex I inactivation
additional information
-
reduction in complex I activity results in a decrease in mitochondrial movement which is compensated for by an increase in mitochondrial length and degree of branching and an enhanced diffusion of matrix constituents
additional information
-
an assembled complex IV helps to maintain complex I in mammalian cells
medicine
-
mitochondrial complex I plays an important role in modulating Toll-like receptor 4-mediated neutrophil activation. Metformin, as well as other agents that inhibit mitochondrial complex I, may be useful in the prevention or treatment of acute inflammatory processes in which activated neutrophils play a major role, such as acute lung injury
additional information
-
an assembled complex IV helps to maintain complex I in mammalian cells
medicine
-
enzymes activated by DNA damage, e.g. mediated by complex I inhibition, are an important feature in the process of neuronal apoptosis
additional information
-
crucial role for mitochondrial nitric oxide synthase in oxidative stress caused by mitochondrial complex I inactivation
additional information
-
two variants of the mitochondrial complex I subunit NDUFA10. A D/N substitution at position 120 resulting from a 353A/G transition in the coding gene is the biochemical difference between the two most abundant NDUFA10 isoforms