lipo-PDH decarboxylates PYR to Ac-CoA

Stable Identifier
Homo sapiens
pyruvate + CoASH + NAD+ => acetylCoA + CO2 + NADH + H+, Oxidative decarboxylation of pyruvate to acetyl CoA by pyruvate dehydrogenase
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The mitochondrial pyruvate dehydrogenase complex catalyzes the reaction of pyruvate, CoASH, and NAD+ to form acetylCoA, CO2, and NADH. The enzyme complex contains multiple copies of three different proteins, E1 alpha, E1 beta, E2, and E3, each with distinct catalytic activities (Reed and Hackert 1990; Zhou et al 2001). The reaction starts with the oxidative decarboxylation of pyruvate catalyzed by E1 alpha and beta (pyruvate dehydrogenase). Lipoamide cofactor associated with E1 is reduced at the same time. Next, the acetyl group derived from pyruvate is transferred to coenzyme A in two steps catalyzed by E2 (dihydrolipolyl transacetylase). Finally, the oxidized form of lipoamide is regenerated and electrons are transferred to NAD+ in two steps catalyzed by E3 (dihydrolipoyl dehydrogenase). The biochemical details of this reaction have been worked out with pyruvate dehydrogenase complex and subunits purified from bovine tissue and other non-human sources. Direct evidence for the roles of the corresponding human proteins comes from studies of patients expressing mutant forms of E1 alpha (Lissens et al. 2000), E1 beta (Brown et al. 2004), E2 (Head et al. 2005), and E3 (Brautigam et al. 2005).

Literature References
PubMed ID Title Journal Year
2188967 Structure-function relationships in dihydrolipoamide acyltransferases.

Reed, LJ, Hackert, ML

J Biol Chem 1990
16049940 Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency

Head, RA, Brown, RM, Zolkipli, Z, Shahdadpuri, R, King, MD, Clayton, PT, Brown, GK

Ann Neurol 2005
15138885 Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency

Brown, RM, Head, RA, Boubriak, II, Leonard, JV, Thomas, NH, Brown, GK

Hum Genet 2004
15946682 Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations

Brautigam, CA, Chuang, JL, Tomchick, DR, Machius, M, Chuang, DT

J Mol Biol 2005
11752427 The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes.

Zhou, ZH, McCarthy, DB, O'Connor, CM, Reed, LJ, Stoops, JK

Proc Natl Acad Sci U S A 2001
10679936 Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency

Lissens, W, De Meirleir, L, Seneca, S, Liebaers, I, Brown, GK, Brown, RM, Ito, M, Naito, E, Kuroda, Y, Kerr, DS, Wexler, ID, Patel, MS, Robinson, BH, Seyda, A

Hum Mutat 2000
Participant Of
Catalyst Activity
Catalyst Activity
pyruvate dehydrogenase activity of lipo-PDH [mitochondrial matrix]
Physical Entity
Orthologous Events
Cross References