PDHA1 / PDH E1 ALPHA Antibody – Rabbit Polyclonal

PDHA1: a mitochondrial matrix enzyme that catalyzes the oxidative decarboxylation of pyruvate, producing acetyl-CoA and CO2. A key enzyme in controlling the balance between lipid and glucose oxidation depending on substrate availability. The pyruvate dehydrogenase (PDH) holoenzyme is a multi-enzyme complex (PDHC) that 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. The activity of PDH is tightly regulated by phosphorylation. The phosphorylation of at least one of three specific serine residues in E1 subunit by PDHK inactivates the PDHC, while dephosphorylation by PDP restores its activity. Sites 1, 2, and 3 of PDHA1 are S293, S300, and S232, respectively. Four PDHK isoenzymes have been described, each with different site specificity: all four phosphorylate sites 1 and 2 but at different rates; for site 1 PDHK2 >PDHK4 >PDHK1 >PDHK3; for site 2, PDHK3> PDHK4 > PDHK2 > PDHK1. Only PDHK1 phosphorylates site 3. PDHA1 deficiency is the most common enzyme defect in patients with primary lactic acidosis.

Protein type: Amino Acid Metabolism - valine, leucine and isoleucine biosynthesis; Carbohydrate Metabolism - pyruvate; EC 1.2.4.1; Carbohydrate Metabolism - citrate (TCA) cycle; Mitochondrial; Carbohydrate Metabolism - glycolysis and gluconeogenesis; Carbohydrate Metabolism - butanoate; Oxidoreductase

Chromosomal Location of Human Ortholog: Xp22.1

Cellular Component: mitochondrial matrix; mitochondrion; myelin sheath; nucleus; pyruvate dehydrogenase complex

Molecular Function: pyruvate dehydrogenase (acetyl-transferring) activity; pyruvate dehydrogenase activity

Biological Process: acetyl-CoA biosynthetic process from pyruvate; cellular metabolic process; glucose metabolic process; glyoxylate metabolic process; pyruvate metabolic process; regulation of acetyl-CoA biosynthetic process from pyruvate; tricarboxylic acid cycle

Disease: Pyruvate Dehydrogenase E1-alpha Deficiency