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

Basic Information

Enzyme Number

Official Name

dihydrolipoyl dehydrogenase

Name from literature

branched-chain alpha-keto acid dehydrogenase complex

Pathway from literature

the branched-chain amino acid catabolism

Pathway from KEGG

Amino Acid Metabolism; Glycine, serine and threonine metabolism; map00260

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

Carbohydrate Metabolism; Pyruvate metabolism; map00620

Carbohydrate Metabolism; Glycolysis / Gluconeogenesis; map00010

Carbohydrate Metabolism; Citrate cycle (TCA cycle); map00020

Amino Acid Metabolism; Alanine and aspartate metabolism; map00252


Human (9606)

Genome localization

7q31-q32[1738 ],


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, 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 (click here for diagram), in which it acts, together with EC, glycine dehydrogenase (decarboxylating), and EC, 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, the T protein (EC, the L protein (EC and the lipoyl-bearing H protein [6].

Rate-limiting Description

"The rate-limiting step of branched-chain amino acid oxidation is performed by the mitochondrial enzyme branched-chain alpha-keto acid dehydrogenase (BCKAD), which is regulated by a deactivating kinase." (11641455)

Regulatory Information

Regulatory type


transcriptional factor;

"Only 33% of the functional variants were found in known consensus transcription factor binding sequences or motifs, which suggests that either there are many unknown transcription factor binding motifs or other, unknown mechanisms are involved. The genes with functional polymorphisms that are reported here for the first time include AGTRL2, CAT, CHRNA5, CTSG, CYP2D6, DLD, ERCC1, GABRA1, GABRP, HNRPH3, HIP1, IGKV1-9, KCNJ15, KCNK6, KLK1, MSMB, MYOC, NPY2R, NOTCH4, ORM2, PEDF, PTPRCAP, ST16 (IL24), SULT1A1, and TSHR." (16086313)

Gene ontology

Gene ontology

GO:0050660 (F) FAD binding [P09622 ];
GO:0009055 (F) electron carrier activity [P09622 ];
GO:0005759 (C) mitochondrial matrix [P09622 ];
GO:0055114 (P) oxidation reduction [P09622 ];
GO:0045454 (P) cell redox homeostasis [P09622 ];
GO:0004148 (F) dihydrolipoyl dehydrogenase activity [P09622 ];

Subcellular localization


mitochondrion [P09622 ];

Disease relevance


Defects in DLD are a cause of congenital infantile lactic acidosis [P09622 ];

Defects in DLD are a cause of maple syrup urine disease (MSUD) [MIM:248600]. MSUD is characterized by mental and physical retardation, feeding problems and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine, resulting from a block in oxidative decarboxylation [P09622 ];




Entrez Gene




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