Pyruvate dehydrogenase complex

A multienzyme assembly that converts pyruvate into acetyl-CoA, producing carbon dioxide and NADH. It links glycolysis to the citric acid cycle and irreversibly commits carbon to oxidation.

Pyruvate decarboxylation: The removal of a carboxyl group from pyruvate, releasing carbon dioxide and leaving a two-carbon fragment. The first chemical step releases carbon dioxide and transfers the remaining fragment to the complex.
Glycolysis: A pathway that breaks glucose into pyruvate while generating ATP and NADH. It supplies the pyruvate that enters the complex.
Pyruvate dehydrogenase deficiency: A group of inherited disorders caused by impaired conversion of pyruvate to acetyl-CoA. Defects in complex components can cause this disorder, often with lactic acidosis and neurological impairment.
Lester Reed: An American biochemist who studied the structure and catalytic mechanism of the pyruvate dehydrogenase complex. His research helped establish how the complex’s components cooperate in catalysis.
Thiamine pyrophosphate: A coenzyme derived from vitamin B1 that stabilizes reactive carbon intermediates in enzyme-catalyzed reactions. Its reactive thiazolium ring carries the two-carbon fragment after decarboxylation.
Acetyl-CoA: A coenzyme-bound two-carbon acetyl group used in energy metabolism and biosynthesis. It is the complex’s principal carbon-containing product.
Lactic acidosis: A metabolic acidosis associated with elevated lactate in blood or tissues. When pyruvate oxidation is impaired, more pyruvate can be converted to lactate.
Robert B. Woodward: An American biochemist whose laboratory investigated the structure and mechanism of multienzyme complexes. His group’s work contributed to defining the complex’s organized architecture.
Lipoamide: A protein-bound cofactor whose flexible arm carries acyl groups and reducing equivalents between enzyme active sites. Its swinging arm transfers the acetyl group between catalytic centers.
Citric acid cycle: A cyclic pathway that oxidizes acetyl-CoA to carbon dioxide and captures energy in reduced cofactors. It receives the acetyl group produced by the complex.

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