Information on EC 2.7.11.4 - [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase

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The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY
2.7.11.4
-
RECOMMENDED NAME
GeneOntology No.
[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] = ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphotransferase
The enzyme has no activating compound but is specific for its substrate. It is a mitochondrial enzyme associated with the branched-chain 2-oxoacid dehydrogenase complex. Phosphorylation inactivates EC 1.2.4.4, 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring).
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
BCK
-
-
-
-
BCKD kinase
-
-
BCKD kinase
-
-
BCKD kinase
-
-
BCKD-kinase
-
-
BCKDH kinase
-
-
-
-
BCKDH kinase
-
-
BCOAD
-
-
branched chain ketoacid dehydrogenase kinase
-
-
branched-chain 2-oxo acid dehydrogenase kinase
-
-
-
-
branched-chain alpha-keto acid decarboxylase/dehydrogenase kinase
-
-
branched-chain alpha-keto acid dehydrogenase
-
-
branched-chain alpha-keto acid dehydrogenase kinase
-
-
-
-
branched-chain alpha-keto acid dehydrogenase kinase
-
-
branched-chain alpha-ketoacid dehydrogenase kinase
-
-
-
-
branched-chain alpha-ketoacid dehydrogenase kinase
-
-
branched-chain alpha-ketoacid dehydrogenase kinase
-
-
branched-chain alpha-ketoacid dehydrogenase kinase
-
-
branched-chain keto acid dehydrogenase kinase
-
-
-
-
branched-chain oxoacid dehydrogenase complex
-
-
branched-chain oxoacid dehydrogenase kinase
-
-
kinase, branched-chain oxo acid dehydrogenase (phosphorylating)
-
-
-
-
additional information
-
kinase activity is an intrinsic activity of branched-chain oxo acid dehydrogenase complex
CAS REGISTRY NUMBER
COMMENTARY
82391-38-6
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
mouse, C57BL/6J
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
mouse, C57BL/6J
-
-
Manually annotated by BRENDA team
clone 9 cells express higher amounts of the enzyme after insulin treatment
-
-
Manually annotated by BRENDA team
female Sprague-Dawley
-
-
Manually annotated by BRENDA team
male Wistar
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
the BDK activity is decreased in the livers of streptozotocin-induced diabetic rats
malfunction
-
patients with homozygous BCKDK mutations display reductions in BCKDK messenger RNA and protein, E1alpha phosphorylation, and plasma branched-chain amino acids. Inactivating mutations in the gene BCKDK in consanguineous families are associated with autism, epilepsy, and intellectual disability, geno- and phenotyping, overview
physiological function
-
branched-chain alpha-keto acid dehydrogenase kinase is responsible for the regulation of branched-chain alpha-keto acid dehydrogenase complex, which is the rate-limiting enzyme in the catabolism of branched-chain amino acids
metabolism
-
the enzyme is involved in the regulation of the branched-chain alpha-keto acid dehydrogenase complex by inactivating it through phopshorylation, complex regulation and effects of the drug benzofibrate, overview
additional information
-
activity of BDK practically corresponds with plasma insulin concentrations
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
-
-
-
-
?
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
-
inactivation of the substrate enzyme
-
-
?
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
-
the catalyzed reversible specific phosphorylation of the BCKD subunit regulates the first committed step in the pathway for leucine, isoleucine, and valine catabolism
-
-
?
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
-
the enzyme catalyzes the regulatory inactivation of the rate limiting enzyme in branched-chain amino acid catabolism, phosphorylation of the branched-chain alpha-keto acid dehydrogenase complex leads to its inactivation, BDK itself is regulated via protein-protein interaction with the BCKD complex
-
-
?
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
-
recombinant human wild-type and mutant substrate proteins, overview, phosphorylation at Ser301 and Ser302 in the phosphorylation loop of decarboxylase E1b component of the large branched-chain alpha-keto acid dehydrogenase complex, loop structure, overview
-
-
?
ATP + histone II-S
?
show the reaction diagram
-
-
-
-
?
ATP + histone II-S
?
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
inactivation by phosphorylation of BCKDH
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
phosphorylation-mediated inactivation of the E1alpha subunit of branched-chain ketoacid dehydrogenase, BCKDH, phosphorylation of residue Ser293 of the E1alpha subunit of branched-chain ketoacid dehydrogenase, BCKDH
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylates alpha-subunit of multienzyme complex component E1
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylates alpha-subunit of multienzyme complex component E1
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
2 Ser-residues in E1-alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
incorporates 0.8 mol phosphate/mol alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
tight binding to multienzyme complex is required for phosphorylation, free enzyme is inactive
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
Ser-residues of MW 46000-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
Ser-residues of MW 46000-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
GTP cannot replace ATP
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylates alpha-subunit of multienzyme complex component E1 and additional sites not associated with inactivation of the enzyme
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylates exclusively MW 47000 subunit of substrate
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
incorporates 0.75 mol phosphate per mol phosphorylation site and 1.5 mol/mol alpha-subunit
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
branched-chain amino acid metabolism
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
branched-chain amino acid metabolism
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
regulatory enzyme of branched-chain 2-oxoacid dehydrogenase complex
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
regulatory enzyme of branched-chain 2-oxoacid dehydrogenase complex
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylation inactivates EC 1.2.4.4
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylation inactivates EC 1.2.4.4
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylation inactivates EC 1.2.4.4
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-, phosphorylation inactivates EC 1.2.4.4
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
-
?
additional information
?
-
-
R288A mutant of E1 is not phosphorylated by the enzyme
-
-
-
additional information
?
-
Q00972
enzyme has also ATPase activity in absence of E1
-
-
-
additional information
?
-
-
BCKD kinase transcription regulation, overview
-
-
-
additional information
?
-
-
The branched-chain alpha-keto acid dehydrogenase complex is the most important regulatory enzyme in branched-chain amino acid catabolism, regulation of hepatic BCKDH complex activity in spontaneous type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats and Zucker diabetic fatty rats, both showing reduced enzyme activity, overview
-
-
-
additional information
?
-
-
the branched-chain oxoacid dehydrogenase complex, BCOAD, is rate determining for the oxidation of branched-chain amino acids in skeletal muscle
-
-
-
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
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
-
inactivation of the substrate enzyme
-
-
?
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
-
the catalyzed reversible specific phosphorylation of the BCKD subunit regulates the first committed step in the pathway for leucine, isoleucine, and valine catabolism
-
-
?
ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase
ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase
show the reaction diagram
-
the enzyme catalyzes the regulatory inactivation of the rate limiting enzyme in branched-chain amino acid catabolism
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
inactivation by phosphorylation of BCKDH
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
show the reaction diagram
-
phosphorylation-mediated inactivation of the E1alpha subunit of branched-chain ketoacid dehydrogenase, BCKDH
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
branched-chain amino acid metabolism
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
branched-chain amino acid metabolism
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
regulatory enzyme of branched-chain 2-oxoacid dehydrogenase complex
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
regulatory enzyme of branched-chain 2-oxoacid dehydrogenase complex
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylation inactivates EC 1.2.4.4
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylation inactivates EC 1.2.4.4
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
-
phosphorylation inactivates EC 1.2.4.4
-
-
?
ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]
ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
phosphorylation inactivates EC 1.2.4.4
-
-
?
additional information
?
-
-
BCKD kinase transcription regulation, overview
-
-
-
additional information
?
-
-
The branched-chain alpha-keto acid dehydrogenase complex is the most important regulatory enzyme in branched-chain amino acid catabolism, regulation of hepatic BCKDH complex activity in spontaneous type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats and Zucker diabetic fatty rats, both showing reduced enzyme activity, overview
-
-
-
additional information
?
-
-
the branched-chain oxoacid dehydrogenase complex, BCOAD, is rate determining for the oxidation of branched-chain amino acids in skeletal muscle
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Calmodulin
-
activation
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
EGTA
-
activation, presumably by chelation of Ca2+
K+
-
activation, 0.1 M
Mg2+
-
-
Mg2+
-
maximum activity at 1.5 mM, inhibits above 1.5 mM
Mg2+
-
Km-value: 0.025 mM; requirement, actual substrate: MgATP2-
Mg2+
-
requirement, actual substrate: MgATP2-
Mg2+
-
requirement, actual substrate: MgATP2-
Mg2+
-
requirement, actual substrate: MgATP2-
Rb+
-
activation
Mg2+
-
required
additional information
-
no activation by Ca2+
additional information
-
no activation by Li+, Na+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-(N-Morpholino)propane sulfonate buffer
-
-
2-Chloroisohexanoate
-
no inhibition by (R)(-)-2-chloroisopentanoate; potassium phosphate increases sensitivity to this inhibitor
2-Chloroisohexanoate
-
no inhibition by (R)(-)-2-chloroisopentanoate; potassium phosphate increases sensitivity to this inhibitor; (R)(+)-isomer is twice as effective as (S)(-)-isomer; site-specific inhibitor
2-Chloroisohexanoate
-
-
2-Chloroisohexanoate
-
-
2-Chloroisohexanoate
-
ATP does not protect; i.e. 2-chloro-4-methylpentanoate, strong
2-Chloroisohexanoate
-
enhanced by monovalent cations and further enhanced by phosphate
2-Chloroisohexanoate
-
50% inhibition at 0.014 mM, no inhibition with histone II-S as substrate
2-Chloroisohexanoate
-
50% inhibition at 0.014 mM
2-oxo-3-methylpentanoate
-
more effective than 2-oxoisopentanoate
2-oxo-3-methylpentanoate
-
-
2-oxo-3-methylpentanoate
-
-
2-oxoisocaproate
-
more effective than 2-oxo-3-methylpentanoate and 2-oxoisopentanoate
2-oxoisocaproate
-
-
2-oxoisocaproate
-
kinetics, 40% inhibition at 0.065 mM
2-oxoisopentanoate
-
less effective than 2-oxoisohexanoate and 2-oxo-3-methylpentanoate
2-oxoisopentanoate
-
-
2-oxoisopentanoate
-
-
2-Oxopentanoate
-
kinetics
3-methyl-2-oxobutanoate
-
-
4-(2-Thienyl)-2-oxo-3-butenoate
-
2 mM
4-(3-Thienyl)-2-oxo-3-butenoate
-
2 mM
4-hydroxyphenylacetate
-
-
4-hydroxyphenyllactate
-
weak
4-hydroxyphenylpyruvate
-
-
4-hydroxyphenylpyruvate
-
very weak: 3-hydroxyphenylpyruvate
4-methyl-2-oxopentanoate
-
-
acetate
-
weak, in vivo and in vitro
acetoacetyl-CoA
-
40% inhibition at 0.01 mM
ADP
Q00972
product inhibition
ADP
-
50% inhibition at 0.4 mM, inhibition can be reversed by 2 mM Mg2+
alpha-Chloroisocaproate
-
inhibits the enzyme by releasing it from the BCKD complex via dissociation
alpha-Chloroisocaproate
-
-
alpha-Ketoisocaproate
-
inhibits the enzyme by releasing it from the BCKD complex via dissociation
alpha-ketoisovalerate
-
inhibits the enzyme by releasing it from the BCKD complex via dissociation
ATP
-
50% inhibition at 0.2 mM, inhibition can be reversed by 2 mM Mg2+
branched-chain 2-oxo acids
-
-
branched-chain 2-oxo acids
-
-
CDP
-
50% inhibition at 0.4 mM, inhibition can be reversed by 2 mM Mg2+
Clofibric acid
-
in vivo and in vitro
CTP
-
50% inhibition at 0.25 mM, inhibition can be reversed by 2 mM Mg2+
dexamethasone
-
decreases enzyme expression level in renal tubule cells
Dichloroacetate
-
ATP slightly protects
Dichloroacetate
-
50% inhibition at 1.8 mM
diphosphate
-
-
Furfurylidenepyruvate
-
1.85 mM
GDP
-
50% inhibition at 0.2 mM, inhibition can be reversed by 2 mM Mg2+
GTP
-
50% inhibition at 0.06 mM, inhibition can be reversed by 2 mM Mg2+
heparin
-
40% inhibition at 0.012 mg/ml
heparin
-
50% inhibition at 0.002 mM
methylmalonyl-CoA
-
40% inhibition at 0.2 mM
Mg2+
-
at concentrations above 1.5 mM, activation below
n-Octanoate
-
40% inhibition at 0.5 mM
NADP+
-
40% inhibition at 1.5 mM
phenylacetate
-
strong
Phenyllactate
-
strong
phenylpyruvate
-
in vivo and in vitro
thiamine
-
-
thiamine diphosphate
-
inhibits phosphorylation of wild-type E1, mutant E1-S303A and mutant E1-D296A/S303A, but not phosphorylation of mutant E1-H292A
thiamine diphosphate
-
-
thiamine diphosphate
-
-
thiamine diphosphate
-
-
UDP
-
50% inhibition at 0.25 mM, inhibition can be reversed by 2 mM Mg2+
UTP
-
50% inhibition at 0.1 mM, inhibition can be reversed by 2 mM Mg2+
MgATP2-
-
-
additional information
-
no inhibition by 2-chloropropionate
-
additional information
-
no inhibition by GTP
-
additional information
-
no inhibition by acetyl-CoA; no inhibition by coenzyme A
-
additional information
-
no inhibition by lactate
-
additional information
-
-
-
additional information
-
no inhibition by acetate; no inhibition by acetyl-CoA; no inhibition by lactate; no inhibition by methylcrotonyl-CoA, beta-hydroxy-beta-methylglutaryl-CoA, crotonyl-CoA, octanoyl-CoA, succinyl-CoA, propionyl-CoA, 0.1 mM each, propionate, beta-hydroxybutyrate, acetoacetate, malonate, alpha-ketomalonate, succinate, citrate, oxaloacetate, FAD+, NADPH, 2 mM; no inhibition by NADH, NAD+ 1 mM each
-
additional information
-
no inhibition by DL-leucine
-
additional information
-
binding of thiamin diphosphate cofactor to branched-chain alpha-keto acid decarboxylase/dehydrogenase, which induces a phosphorylation loop conformation change, inhibits the phosphorylation of the protein by the BCKD kinase, no inhibition of phosphorylation of mutant R287A, D295A, Y300F, and R301A E1B components
-
additional information
-
clofibric acid and thiamine diphosphate do not affect the protein-protein interaction of BDK with the BCKD complex
-
additional information
-
no inhibition by coenzyme A; no inhibition by isovaleryl-CoA
-
additional information
-
no inhibition by isovaleryl-CoA
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
poly-L-arginine
-
1.5 to 3fold
poly-L-lysine
-
1.5 to 3fold
protamine
-
1.5 to 3fold
Histone H3
-
1.5 to 3fold
-
additional information
-
tissue-specific translation of branched-chain alpha-ketoacid dehydrogenase kinase mRNA is dependent upon an upstream open reading frame in the 5'-untranslated region
-
additional information
-
exercise training increases branched-chain oxoacid dehydrogenase kinase content in human skeletal muscle, mechanism, overview
-
additional information
-
dietary supplementation of branched-chain amino acid over several weeks increases the enzyme activity in spontaneous type II diabetic rats, overview
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.025
-
ATP
-
pH 7.35, 20C
0.025
-
ATP
-
pH 7.5, 30C
0.0126
-
MgATP2-
-
pH 7.5, 30C
0.013
-
MgATP2-
-
pH 7.5, 30C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0542
-
phosphate
-
25C, recombinant enzyme alone
0.475
-
phosphate
-
25C, reconstituted with lipoylated recombinant E2
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.5
-
2-Chloroisohexanoate
-
37C
0.00092
-
2-oxoisocaproate
-
pH 7.5, 30C
0.00048
-
4-methyl-2-oxopentanoate
-
pH 7.5, 30C
0.0089
-
4-methyl-2-oxopentanoate
-
pH 7.5, 30C
0.00027
-
ADP
-
pH 7.5, 30C
0.13
-
ADP
-
pH 7.35, 20C
0.13
-
ADP
-
pH 7.5, 30C
0.27
-
ADP
-
pH 7.5, 30C
0.004
-
diphosphate
-
pH 7.5, 30C
4.5
-
Furfurylidenepyruvate
-
-
0.0059
-
thiamine
-
pH 7.5, 30C
0.0032
-
thiamine diphosphate
-
20 mM K+
0.0164
-
thiamine diphosphate
-
100 mM K+
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.006
-
alpha-Chloroisocaproate
-
100 mM K+
0.031
-
alpha-Chloroisocaproate
-
10 mM K+
0.0046
-
thiamine diphosphate
-
20 mM K+
0.008
-
thiamine diphosphate
-
100 mM K+
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0247
-
-
without added salt
0.0268
-
-
liver enzyme
0.0357
0.09
-
heart enzyme, depending on purification method
0.0357
-
-
heart enzyme
0.05
-
-
recombinant enzyme
additional information
-
-
various assay methods
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
additional information
-
-
in decreasing order of activity: HEPES, potassium phosphate, imidazole, 3-(N-morpholino)ethane buffer
additional information
-
-
HEPES-potassium buffer promotes higher activity than imidazole-chloride, 4-morpholinopropanesulfonic acid-potassium or potassium phosphate buffer
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
8.3
-
about half-maximal activity at pH 6.5 and 8.3
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
assay at room temperature
30
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.5
-
-
native PAGE
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
liver cell line
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
;
-
Manually annotated by BRENDA team
-
undifferentiated myoblast cell line
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
;
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
;
-
Manually annotated by BRENDA team
-
enzyme activity is 3-5fold higher in female than in male rats
Manually annotated by BRENDA team
-
malnutrition results in changed amounts of enzyme level
Manually annotated by BRENDA team
-
type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats and Zucker diabetic fatty rats
Manually annotated by BRENDA team
-
activity of BDK is higher in fatty diabetic rats than in lean non-diabetic rats
Manually annotated by BRENDA team
Mus musculus C57BL/6J, Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
LLC-PK1 renal tubule cell line expressing the Rattus norvegicus glucocorticoid receptor GR
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
fibroblast cell line
Manually annotated by BRENDA team
-
enzyme content decreases 0.7fold after running exercise for 5 weeks
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
enzyme content decreases 0.7fold after running exercise for 5 weeks
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
additional information
-
enzyme expression analysis
Manually annotated by BRENDA team
additional information
-
tissue distribution, tissue-specific translation of branched-chain alpha-ketoacid dehydrogenase kinase mRNA is dependent upon an upstream open reading frame in the 5'-untranslated region, thus mRNA and protein level do not correlate
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
2 forms: first form is bound to E2, second form is free and seems to be inactive
Manually annotated by BRENDA team
-
part of intramitochondrial branched-chain 2-oxoacid dehydrogenase complex
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
;
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
43280
-
-
calculated from amino acid sequence
44000
45000
-
SDS-PAGE
460000
-
-
gel filtration
2000000
-
-
above 2000000, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 44000, SDS-PAGE
?
Rattus norvegicus Sprague-Dawley
-
x * 44000, SDS-PAGE
-
dimer
Q00972
dimerizes through direct interaction of two opposing nucleotide-binding domains, crystallographic data
monomer
-
1 * 43000, uncomplexed kinase, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
vapor diffusion method
Q00972
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
loss of activity during purification at pH-values below 7
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
precipitation of branched-chain oxo acid dehydrogenase enzyme complex at acid pH-values, especially below 6.5, results in specific loss of kinase activity
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
labile enzyme, best stored at -70C in the presence of DTT
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
5000fold
-
copurifies with EC 1.2.4.4
-
alpha-ketoacid dehydrogenase complex
-
alpha-ketoacid dehydrogenase complex
-
from liver and heart, homogeneity
-
from purified branched-chain alpha-keto acid dehydrogenase complex
-
liver enzyme, heart enzyme and recombinant enzyme expressed in Escherichia coli
-
partially from mitochondria
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
DNA sequence determination and analysis, promotor region footprinting, expression analysis, mechanism of the enzyme expression regulation
-
BDK quantitative real-time PCR expression analysis
-
BDK semi-quantitative real-time PCR expression analysis
-
cloned and expressed in Escherichia coli
-
fragments of the enzyme cloned into firefly luciferase plasmid
-
fusion protein with maltose-binding protein
-
BCKD kinase transcription regulation, overview
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme expression is reduced by 5% by bezafibrate
-
insulin is known to increase the enzyme expression in cultured rat hepatocytes
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
R224P
-
naturally occuring mutation, leading to disruption of the beta sheet in a flexible linker domain, structure modeling
G671C
-
naturally occuring mutation, on chromosome 16, leads to the substitution of a highly conserved arginine with a proline at position 224 in BCKDK
additional information
-
identification of mutations from autism patients , e.g. in exon 4 (C466T) resulting in a premature stop codon at amino acid position 156, prior to the kinase domain, or a single base deletion (c.G222del) in exon 2 leading to frame-shift terminating the protein at position 74 of 412 amino acids, whole-exome sequencing from two consanguineous families
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
reconstitution with lipoylated recombinant E2
-