Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.2.4.4

Official Name

3-methyl-2-oxobutanoate dehydrogenase

Name from literature

branched chain oxoacid dehydrogenase

Pathway from literature

BCAA oxidation/branched-chain amino acid catabolism

Pathway from KEGG

Amino Acid Metabolism; Valine, leucine and isoleucine degradation; map00280

Organisms

Human (9606)

Genome localization

19q13.1-q13.2[593 ], 6q13-q15[594 ],

Comments

Contains thiamine diphosphate. It acts not only on 3-methyl-2-oxobutanaoate, but also on 4-methyl-2-oxopentanoate and (S)-3-methyl-2-oxopentanoate, so that it acts on the 2-oxo acids that derive from the action of transaminases on valine, leucine and isoleucine. It is a component of the multienzyme 3-methyl-2-oxobutanoate dehydrogenase complex in which multiple copies of it are bound to a core of molecules of EC 2.3.1.168, dihydrolipoyllysine-residue (2-methylpropanoyl)transferase, which also binds multiple copies of EC 1.8.1.4, dihydrolipoyl dehydrogenase. It does not act on free lipoamide or lipoyllysine, but only on the lipoyllysine residue in EC 2.3.1.168.

Rate-limiting Description

"We have previously shown that BCAA ingestion increased the activity of branched-chain oxoacid dehydrogenase, the rate-limiting enzyme for BCAA oxidation in muscle, compared with low glycogen alone." (10562606)

Regulatory Information

Regulatory type

Detail

phosphorylation;

"analysis of roles of His291-alpha and His146-beta' in the reductive acylation reaction catalyzed by human branched-chain alpha-ketoacid dehydrogenase: refined phosphorylation loop structure in the active site" (12902323)

phosphorylation;

"cross-talk between thiamin diphosphate binding and phosphorylation loop conformation has an effect on human branched-chain alpha-keto acid decarboxylase/dehydrogenase" (15166214)

phosphorylation;

P12694

phosphorylation;

P21953

phosphorylation;

P12694:from_uniprot:337_Phosphoserine

phosphorylation;

P12694:from_uniprot:345_Phosphotyrosine

phosphorylation;

P12694:from_uniprot:347_Phosphoserine

Gene ontology

Gene ontology

GO:0016831 (F) carboxy-lyase activity [P21953, P12694 ];
GO:0005947 (C) mitochondrial alpha-ketoglutarate dehydroge... [P21953, P12694 ];
GO:0009083 (P) branched chain family amino acid catabolic ... [P21953, P12694 ];
GO:0003863 (F) 3-methyl-2-oxobutanoate dehydrogenase (2-me... [P21953, P12694 ];
GO:0003826 (F) alpha-ketoacid dehydrogenase activity [P12694 ];
GO:0030955 (F) potassium ion binding [P12694 ];
GO:0005515 (F) protein binding [P21953, P12694 ];
GO:0055114 (P) oxidation reduction [P21953, P12694 ];

Subcellular localization

Localization

mitochondrion [P21953, P12694 ];

Disease relevance

Disease

Defects in BCKDHA are a cause of maple syrup urine disease type IA (MSUD1A) [MIM:248600]. MSUD is an autosomal recessive disorder characterized by mental and physical retardation, feeding problems, and a maple syrup odor to the urine [P12694 ];

Defects in BCKDHB are the cause of maple syrup urine disease type IB (MSUD1B) [MIM:248600]. MSUD is an autosomal recessive disorder characterized by mental and physical retardation, feeding problems, and a maple syrup odor to the urine [P21953 ];

Links

SwissProt

P12694; P21953

Entrez Gene

593; 594

HPRD

02009; 02011



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min