DLD
Function
Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex) (PubMed:15712224, PubMed:16442803, PubMed:16770810, PubMed:17404228, PubMed:20160912, PubMed:20385101). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711). In monomeric form may have additional moonlighting function as serine protease (PubMed:17404228). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity).
Involvement in disease
Dihydrolipoamide dehydrogenase deficiency
DLDD
An autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Tyrosine phosphorylated.
Sequence Similarities
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
Cellular localization
- Mitochondrion matrix
- Nucleus
- Cell projection
- Cilium
- Flagellum
- Cytoplasmic vesicle
- Secretory vesicle
- Acrosome
- Mainly localizes in the mitochondrion. A small fraction localizes to the nucleus, where the 2-oxoglutarate dehydrogenase complex is required for histone succinylation.
Alternative names
GCSL, LAD, PHE3, DLD, Dihydrolipoamide dehydrogenase, Glycine cleavage system L protein