Diaphorase (DLD) Enzyme

This gene encodes the L protein of the mitochondrial glycine cleavage system. The L protein, also named dihydrolipoamide dehydrogenase, is also a component of the pyruvate dehydrogenase complex, the alpha-ketoglutarate dehydrogenase complex, and the branched-chain alpha-keto acide dehydrogenase complex. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. [provided by RefSeq, Jul 2008]

Function: Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction.

Catalytic activity: Protein N(6)-(dihydrolipoyl)lysine + NAD+ = protein N(6)-(lipoyl)lysine + NADH.

Cofactor: Binds 1 FAD per subunit

By similarity.

Subunit structure: Homodimer. Eukaryotic pyruvate dehydrogenase complexes are organized about a core consisting of the oligomeric dihydrolipoamide acetyl-transferase, around which are arranged multiple copies of pyruvate dehydrogenase, dihydrolipoamide dehydrogenase and protein X bound by non-covalent bonds. Ref.12

Subcellular location: Mitochondrion matrix.

Post-translational modification: Tyrosine phosphorylated

By similarity.

Involvement in disease: Defects in DLD are involved in the development of congenital infantile lactic acidosis.Maple syrup urine disease (MSUD) [MIM:248600]: A metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include 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. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.Note: The disease is caused by mutations affecting the gene represented in this entry.

Miscellaneous: The active site is a redox-active disulfide bond.

Sequence similarities: Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.

Sequence caution: The sequence BAD92940.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.