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Information on EC 1.8.1.4 - dihydrolipoyl dehydrogenase and Organism(s) Rattus norvegicus
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1.8.1.4 dihydrolipoyl dehydrogenaseIUBMB Comments
A flavoprotein (FAD). A component of the multienzyme 2-oxo-acid dehydrogenase complexes. In the pyruvate dehydrogenase complex, it binds to the core of EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase, and catalyses oxidation of its dihydrolipoyl groups. It plays a similar role in the oxoglutarate and 3-methyl-2-oxobutanoate dehydrogenase complexes. Another substrate is the dihydrolipoyl group in the H-protein of the glycine-cleavage system ({AminoAcid/GlyCleave} for diagram), in which it acts, together with EC 1.4.4.2, glycine dehydrogenase (decarboxylating), and EC 2.1.2.10, aminomethyltransferase, to break down glycine. It can also use free dihydrolipoate, dihydrolipoamide or dihydrolipoyllysine as substrate. This enzyme was first shown to catalyse the oxidation of NADH by methylene blue; this activity was called diaphorase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein .
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Word Map
- 1.8.1.4
-
multienzyme
- fad
- acetyltransferase
- dehydrogenases
- alpha-ketoglutarate
- flavin
-
branched-chain
- flavoproteins
- transacetylase
- thioredoxin
-
azotobacter
- vinelandii
- thiamin
-
subcomplexes
-
alpha-keto
- acidosis
- alpha-ketoacids
- succinyltransferase
-
mercuric
-
flavoenzymes
- 2-oxoacids
- trypanothione
- friedreich
-
1.2.4.1
-
subunit-binding
-
two-electron
-
radiofrequency
- medicine
-
ketoacids
- degradation
-
ashkenazi
-
t-proteins
-
myenteric
- analysis
- drug development
- diagnostics
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
lipoamide dehydrogenase, dihydrolipoamide dehydrogenase, dldh, l-protein, dihydrolipoyl dehydrogenase, nadh diaphorase, e3 component, lipdh, nicotinamide adenine dinucleotide diaphorase, lipoyl dehydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dehydrogenase, lipoamide
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dehydrolipoate dehydrogenase
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DHLDH
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diaphorase
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dihydrolipoamide dehydrogenase E3
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common component of the three 2-oxoacid dehydrogenase complexes oxidizing pyruvate, 2-oxoglutarate, and the branched-chain 2-oxo acids
dihydrolipoic dehydrogenase
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dihydrolipoyl dehydrogenase
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DLDH
E3
E3 component of 2-oxoglutarate dehydrogenase complex
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E3 component of acetoin cleaving system
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E3 component of alpha keto acid dehydrogenase complexes
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E3 component of pyruvate and 2-oxoglutarate dehydrogenases complexes
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E3 component of pyruvate complex
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E3 lipoamide dehydrogenase
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Glycine cleavage system L protein
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Glycine oxidation system L-factor
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LDP-Glc
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LDP-Val
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lipoamide dehydrogenase (NADH)
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lipoamide oxidoreductase (NADH)
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lipoamide reductase
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lipoate dehydrogenase
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lipoic acid dehydrogenase
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lipoyl dehydrogenase
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LPD
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LPD-GLC
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LPD-VAL
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NADH:lipoamide oxidoreductase
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ORF-E3
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DLDH
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E3
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY SOURCE
PATHWAYS
KEGG
Biosynthesis of secondary metabolites, Citrate cycle (TCA cycle), Glycine, serine and threonine metabolism, Glycolysis / Gluconeogenesis, Lysine degradation, Microbial metabolism in diverse environments, Propanoate metabolism, Pyruvate metabolism, Tryptophan metabolism, Valine, leucine and isoleucine degradation
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-, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
protein-N6-(dihydrolipoyl)lysine:NAD+ oxidoreductase
A flavoprotein (FAD). A component of the multienzyme 2-oxo-acid dehydrogenase complexes. In the pyruvate dehydrogenase complex, it binds to the core of EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase, and catalyses oxidation of its dihydrolipoyl groups. It plays a similar role in the oxoglutarate and 3-methyl-2-oxobutanoate dehydrogenase complexes. Another substrate is the dihydrolipoyl group in the H-protein of the glycine-cleavage system ({AminoAcid/GlyCleave} for diagram), in which it acts, together with EC 1.4.4.2, glycine dehydrogenase (decarboxylating), and EC 2.1.2.10, aminomethyltransferase, to break down glycine. It can also use free dihydrolipoate, dihydrolipoamide or dihydrolipoyllysine as substrate. This enzyme was first shown to catalyse the oxidation of NADH by methylene blue; this activity was called diaphorase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [6].
CAS REGISTRY NUMBER
COMMENTARY
9001-18-7
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dihydrolipoamide + NAD+
lipoamide + NADH
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?
additional information
?
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the enzyme is a component of the three 2-oxoacid dehydrogenase complexes oxidizing pyruvate, 2-oxoglutarate, and the branched-chain 2-oxo acids
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
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the enzyme is a component of the three 2-oxoacid dehydrogenase complexes oxidizing pyruvate, 2-oxoglutarate, and the branched-chain 2-oxo acids
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Diethylamine NONOate
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induces 71% loss in diaphorase activity at 10 mM, but does not induce any activity loss at 2 mM
H2O2
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enzyme is inactivated by complex III- but not complex I-derived reactive oxygen species, and the accompanying loss of activity due to the inactivation can be restored by cysteine and glutathione. H2O2 instead of superoxide anion is responsible for the inactivation, and protein sulfenic acid formation is associated with the loss of enzymatic activity
S-nitrosocysteine
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induces a 62% loss in diaphorase activity at 2 mM and an 88% loss at 10 mM
S-nitrosoglutathione
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induces 84% loss in diaphorase activity at 10 mM, but does not induce any activity loss at 2 mM
valproyl-dephosphoCoA
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uncompetitive inhibitor, 0.5-1.0 mM inhibit DLDH activity
additional information
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diamide, GSH, GSSG, cysteine and nitrite do not exhibit any inhibitory effects
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additional information
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no age-related decline in DLDH activity or expression is evident in rats over the period from 5 to 30 months of age. Lower DLDH dehydrogenase activity observed in pups may be due to NADH inhibition
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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activity of DLDH dehydrogenase increases in rats between 10 and 20 days of age. Dehydrogenase activity of DLDH shows a further, progressive increase in rats from 20 days to adulthood, in the absence of any further change in DLDH expression or diaphorase activity
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additional information
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activity of DLDH diaphorase is both protein amount- and time-dependent
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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enzyme is not detected on Western blots probed with antibodies that recognize mitochondrial dihydrolipoamide dehydrogenase
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30% increase in DLDH expression in rats between 10 and 20 days of age, whereas there is no further increase during the period from 20 to 60 days. Diaphorase activity shows a 46% increase in rats between 10 and 20 days of age, but there is also no further increase between 20 and 60 days. DLDH dehydrogenase activity increases progressively over the period from 10 to 60 days of age (63% between 10 and 20 days, 30% between 20 and 30 days, and 25% between 30 and 60 days of age)
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significant increase in DLDH dehydrogenase activity in rats only for the period between 30 and 60 days of age
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significant increase in DLDH dehydrogenase activity in rats only for the period between 30 and 60 days of age
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increase in DLDH dehydrogenase activity in rats between 10 and 20 days of age, with no further increase evident thereafter
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
-
synthesized predominantly on free ribosomes and translocated into mitochondria
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
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enzyme is inactivated by complex III- but not complex I-derived reactive oxygen species, and the accompanying loss of activity due to the inactivation can be restored by cysteine and glutathione. H2O2 instead of superoxide anion is responsible for the inactivation, and protein sulfenic acid formation is associated with the loss of enzymatic activity
physiological function
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effects of insulin treatment on HuC/HuD myoenteric neurons, NADH diaphorase, and nNOS-positive myoenteric neurons of the duodenum of adult rats with acute diabetes is investigated: The density of NADH diaphorase-positive neurons in animals from the diabetic group and in the insulin treated diabetic group is greater than in the control group, indicating that short-term diabetes increases the activity of respiratory chain enzymes
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DLDH_RAT
509
0
54038
Swiss-Prot
Mitochondrion (Reliability: 2)
A0A8I5ZXS2_RAT
502
0
53267
TrEMBL
Mitochondrion (Reliability: 3)
A0A8I6A971_RAT
463
0
49189
TrEMBL
Mitochondrion (Reliability: 2)
A0A8I6GBX4_RAT
538
0
57390
TrEMBL
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
56000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
dissociation of the lipoamide dehydrogenase component from the branched-chain alpha-keto acid dehydrogenase complex during purification
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presence of dithiothreitol during purification preserves enzymatic activity
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
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development of a blue native-PAGE-based method for isolation of enzymatically active DLDH from animal tissues and visualization as well as quantification of its diaphorase activity using the NADH/nitroblue tetrazolium detection system
degradation
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decreased activity of DLDH induced by valproic acid metabolites may, at least in part, account for the impaired rate of oxygen consumption and ATP synthesis in mitochondria if 2-oxoglutarate or glutamate are used as respiratory substrates, thus limiting the flux of these substrates through the citric acid cycle
medicine
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brain DLDH expression and activity undergo independent postnatal maturational increases. Senescence does not confer any detectable change in the activity of DLDH or its susceptibility to inactivation by mitochondrial oxidative stress
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ono, K.; Hakozaki, M.; Kimura, A.; Kochi, H.
Purification, resolution, and reconstitution of rat liver branched-chain alpha-keto acid dehydrogenase complex
J. Biochem.
101
19-27
1987
Rattus norvegicus
Carothers, D.J.; Pons, G.; Patel, M.S.
Dihydrolipoamide dehydrogenase: functional similarities and divergent evolution of the pyridine nucleotide-disulfide oxidoreductases
Arch. Biochem. Biophys.
268
409-425
1989
Ascaris suum, Azotobacter vinelandii, Bacillus subtilis, Bos taurus, Escherichia coli, Geobacillus stearothermophilus, Halobacterium salinarum, Homo sapiens, Pisum sativum, Pseudomonas aeruginosa, Pseudomonas putida, Rattus norvegicus, Saccharomyces cerevisiae, Saccharomyces pastorianus, Sus scrofa
Matuda, S.; Saheki, T.
Intracellular distribution and biosynthesis of lipoamide dehydrogenase in rat liver
J. Biochem.
91
553-561
1982
Rattus norvegicus
Williams, C.H.
Flavin-containing dehydrogenases
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
13
89-173
1976
Azotobacter agilis, Azotobacter vinelandii, Bacillus subtilis, Bos taurus, Brassica oleracea, Enterococcus faecalis, Escherichia coli, Escherichia coli B / ATCC 11303, Escherichia coli Crookes, Escherichia coli M191-6, Globisporangium ultimum, Homo sapiens, Leuconostoc mesenteroides, Mycobacterium tuberculosis, Neurospora crassa, Parvimonas micra, Phytophthora erythroseptica, Pichia kudriavzevii, Proteus vulgaris, Pseudomonas fluorescens, Rattus norvegicus, Saccharomyces cerevisiae, Serratia marcescens, Spinacia oleracea, Squalus acanthias, Sus scrofa
-
Luis, P.B.; Ruiter, J.P.; Aires, C.C.; Soveral, G.; de Almeida, I.T.; Duran, M.; Wanders, R.J.; Silva, M.F.
Valproic acid metabolites inhibit dihydrolipoyl dehydrogenase activity leading to impaired 2-oxoglutarate-driven oxidative phosphorylation
Biochim. Biophys. Acta
1767
1126-1133
2007
Rattus norvegicus
Yan, L.J.; Yang, S.H.; Shu, H.; Prokai, L.; Forster, M.J.
Histochemical staining and quantification of dihydrolipoamide dehydrogenase diaphorase activity using blue native PAGE
Electrophoresis
28
1036-1045
2007
Rattus norvegicus
Yan, L.J.; Thangthaeng, N.; Forster, M.J.
Changes in dihydrolipoamide dehydrogenase expression and activity during postnatal development and aging in the rat brain
Mech. Ageing Dev.
129
282-290
2008
Rattus norvegicus
de Mello, S.T.; de Miranda Neto, M.H.; Zanoni, J.N.; Furlan, M.M.
Effects of insulin treatment on HuC/HuD, NADH diaphorase, and nNOS-positive myoenteric neurons of the duodenum of adult rats with acute diabetes
Digest. Dis. Sci.
54
731-737
2009
Rattus norvegicus
Yan, L.J.; Sumien, N.; Thangthaeng, N.; Forster, M.J.
Reversible inactivation of dihydrolipoamide dehydrogenase by mitochondrial hydrogen peroxide
Free Radic. Res.
47
123-133
2013
Rattus norvegicus
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