PDHB siRNA – Pyruvate Dehydrogenase E1 Component Subunit Beta, Mitochondrial Isoform 1 (Human)

The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and carbon dioxide, and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 beta subunit. Mutations in this gene are associated with pyruvate dehydrogenase E1-beta deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2012]

PDHB: the beta subunit of pyruvate dehydrogenase (PDH), 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. Defects in PDHB are a cause of pyruvate dehydrogenase E1 component deficiency (PDHE1 deficiency), the most common enzyme defect in patients with primary lactic acidosis. It is associated with variable clinical phenotypes ranging from neonatal death to prolonged survival complicated by developmental delay, seizures, ataxia, apnea, and in some cases to an X-linked form of Leigh syndrome (LS). Two alternatively spliced human isoforms have been described.

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

Chromosomal Location of Human Ortholog: 3p21.1-p14.2

Cellular Component: nucleoplasm; mitochondrion; mitochondrial matrix; pyruvate dehydrogenase complex; nucleus

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

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

Disease: Pyruvate Dehydrogenase E1-beta Deficiency