If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: pyruvate dehydrogenase complex, acetyl-CoA biosynthesis I (pyruvate dehydrogenase complex)
|Superclasses:||Degradation/Utilization/Assimilation → Carboxylates Degradation|
|Generation of Precursor Metabolites and Energy → Acetyl-CoA Biosynthesis|
This multi-enzyme complex, which consists of 24 subunits of pyruvate dehydrogenase, 24 subunits of lipoate acetyltransferase, and 12 subunits of dihydrolipoate dehydrogenase, catalyzes three reactions, which constitute a cycle. The complex contains a lipoyl active site in the form of lipoyllysine, as well as a thiamin diphosphate.
The net consequence of the cycle, in addition to reducing NAD+, is the conversion of pyruvate into acetyl-CoA and CO2, a key reaction of central metabolism because it links glycolysis I, which generates pyruvate, to the TCA cycle, into which the acetyl-CoA flows.
During aerobic growth the cycle is an essential source of acetyl-CoA to feed the TCA cycle and thereby to satisfy the cellular requirements for the precursor metabolites it forms. Mutant strains defective in the complex require an exogenous source of acetate to meet this requirement, but anaerobically such mutants grow without exogenous acetate because under such conditions, pyruvate formate lyase generates acetyl-CoA from pyruvate. Mutant strains lacking pyruvate formate lyase have the reverse phenotype. They require acetate for anaerobic but not for aerobic growth.
Review: Clark, D.P. and John E. Cronan. EcoSal Module 3.4.4 [ECOSAL]
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Milne02: Milne JL, Shi D, Rosenthal PB, Sunshine JS, Domingo GJ, Wu X, Brooks BR, Perham RN, Henderson R, Subramaniam S (2002). "Molecular architecture and mechanism of an icosahedral pyruvate dehydrogenase complex: a multifunctional catalytic machine." EMBO J 21(21);5587-98. PMID: 12411477
Adamson86: Adamson SR, Holmes CF, Stevenson KJ (1986). "Acetylatable lipoic acid residues interact directly with lipoamide dehydrogenase in the pyruvate dehydrogenase multienzyme complex of Escherichia coli." Biochem Cell Biol 64(3);250-5. PMID: 3087386
Akiyama80: Akiyama SK, Hammes GG (1980). "Elementary steps in the reaction mechanism of the pyruvate dehydrogenase multienzyme complex from Escherichia coli: kinetics of acetylation and deacetylation." Biochemistry 1980;19(18);4208-13. PMID: 6998493
Allen89: Allen AG, Perham RN, Allison N, Miles JS, Guest JR (1989). "Reductive acetylation of tandemly repeated lipoyl domains in the pyruvate dehydrogenase multienzyme complex of Escherichia coli is random order." J Mol Biol 208(4);623-33. PMID: 2509711
Angelides79: Angelides KJ, Akiyama SK, Hammes GG (1979). "Subunit stoichiometry and molecular weight of the pyruvate dehydrogenase multienzyme complex from Escherichia coli." Proc Natl Acad Sci U S A 1979;76(7);3279-83. PMID: 386335
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Bates77: Bates DL, Danson MJ, Hale G, Hooper EA, Perham RN (1977). "Self-assembly and catalytic activity of the pyruvate dehydrogenase multienzyme complex of Escherichia coli." Nature 268(5618);313-6. PMID: 329143
Butland et al., 2005: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043
CaJacob85: CaJacob CA, Frey PA, Hainfeld JF, Wall JS, Yang H (1985). "Escherichia coli pyruvate dehydrogenase complex: particle masses of the complex and component enzymes measured by scanning transmission electron microscopy." Biochemistry 1985;24(10);2425-31. PMID: 3925985
CaJacob85a: CaJacob CA, Gavino GR, Frey PA (1985). "Pyruvate dehydrogenase complex of Escherichia coli. Thiamin pyrophosphate and NADH-dependent hydrolysis of acetyl-CoA." J Biol Chem 260(27);14610-15. PMID: 3902834
Carothers89: Carothers DJ, Pons G, Patel MS (1989). "Dihydrolipoamide dehydrogenase: functional similarities and divergent evolution of the pyridine nucleotide-disulfide oxidoreductases." Arch Biochem Biophys 1989;268(2);409-25. PMID: 2643922
Coggins76: Coggins JR, Hooper EA, Perham RN (1976). "Use of dimethyl suberimidate and novel periodate-cleavable bis(imido esters) to study the quaternary structure of the pyruvate dehydrogenase multienzyme complex of Escherichia coli." Biochemistry 15(12);2527-33. PMID: 779824
deGraef99: de Graef MR, Alexeeva S, Snoep JL, Teixeira de Mattos MJ (1999). "The steady-state internal redox state (NADH/NAD) reflects the external redox state and is correlated with catabolic adaptation in Escherichia coli." J Bacteriol 181(8);2351-7. PMID: 10197995
Diaz-Mejia et al., 2009: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Feeney11: Feeney MA, Veeravalli K, Boyd D, Gon S, Faulkner MJ, Georgiou G, Beckwith J (2011). "Repurposing lipoic acid changes electron flow in two important metabolic pathways of Escherichia coli." Proc Natl Acad Sci U S A 108(19);7991-6. PMID: 21521794
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