Dihydrolipoamide Dehydrogenase (DLD) Human Recombinant Protein

This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DLD: a multi-functional mitochondrial enzyme. An enzymatic component of the mitochondrial glycine cleavage system, the pyruvate dehydrogenase complex (PDHC), the alpha-ketoglutarate dehydrogenase complex, and the branched-chain alpha-keto acide dehydrogenase complex. Is the E3 component of the PDHC that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2. The E3 component has dihydrolipoamide dehydrogenase activity. The PDHC contains 20-30 copies of pyruvate decarboxylase tetramers (2 alpha:2 beta)(E1), 60 copies of dihydrolipoamide acetyltransferase (E2), six homodimers of dihydrolipoamide dehydrogenase (E3), plus E3 binding proteins. Defects in DLD are a cause of maple syrup urine disease (MSUD), 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. Differentially expressed in the Wernicke's Area from patients with schizophrenia. Inhibited by 5-methoxyindole-2-carboxylic acid (MICA).

Protein type: EC 1.8.1.4; Oxidoreductase; Mitochondrial; Carbohydrate Metabolism - glycolysis and gluconeogenesis; Carbohydrate Metabolism - citrate (TCA) cycle; Amino Acid Metabolism - valine, leucine and isoleucine degradation; Carbohydrate Metabolism - pyruvate; Amino Acid Metabolism - glycine, serine and threonine

Chromosomal Location of Human Ortholog: 7q31-q32

Cellular Component: nucleoplasm; mitochondrion; mitochondrial matrix; acrosomal matrix; cilium

Molecular Function: mercury (II) reductase activity; FAD binding; mercury ion binding; dihydrolipoyl dehydrogenase activity; NADP binding

Biological Process: mitochondrial electron transport, NADH to ubiquinone; tricarboxylic acid cycle; regulation of acetyl-CoA biosynthetic process from pyruvate; gastrulation; branched chain family amino acid catabolic process; proteolysis; cellular metabolic process; regulation of membrane potential; cell redox homeostasis; detoxification of mercury ion; lysine catabolic process; pyruvate metabolic process; sperm capacitation

Disease: Dihydrolipoamide Dehydrogenase Deficiency