Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
twitter

Escherichia coli K-12 substr. MG1655 Pathway: pyruvate decarboxylation to acetyl CoA

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

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

Summary:
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]

Citations: [deKok98, Fries03, Milne02]

Credits:
Revised 17-Jan-2006 by Caspi R , SRI International
Revised 14-Jul-2006 by Ingraham JL , UC Davis


References

deKok98: de Kok A, Hengeveld AF, Martin A, Westphal AH (1998). "The pyruvate dehydrogenase multi-enzyme complex from Gram-negative bacteria." Biochim Biophys Acta 1385(2);353-66. PMID: 9655933

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Fries03: Fries M, Jung HI, Perham RN (2003). "Reaction mechanism of the heterotetrameric (alpha2beta2) E1 component of 2-oxo acid dehydrogenase multienzyme complexes." Biochemistry 42(23);6996-7002. PMID: 12795594

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

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

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

Allison88: Allison N, Williams CH, Guest JR (1988). "Overexpression and mutagenesis of the lipoamide dehydrogenase of Escherichia coli." Biochem J 256(3);741-9. PMID: 3066354

Alwine73: Alwine JC, Russell RM, Murray KN (1973). "Characterization of an Escherichia coli mutant deficient in dihydrolipoyl dehydrogenase activity." J Bacteriol 115(1);1-8. PMID: 4197899

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

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

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

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Butland05: 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, 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

CaJacob85a: 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

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

Danson78: Danson MJ, Hooper EA, Perham RN (1978). "Intramolecular coupling of active sites in the pyruvate dehydrogenase multienzyme complex of Escherichia coli." Biochem J 175(1);193-8. PMID: 367364

Danson81: Danson MJ, Hale G, Perham RN (1981). "The role of lipoic acid residues in the pyruvate dehydrogenase multienzyme complex of Escherichia coli." Biochem J 199(3);505-11. PMID: 6803765

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

DiazMejia09: 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

Gershwin00: Gershwin ME, Ansari AA, Mackay IR, Nakanuma Y, Nishio A, Rowley MJ, Coppel RL (2000). "Primary biliary cirrhosis: an orchestrated immune response against epithelial cells." Immunol Rev 174;210-25. PMID: 10807518

Showing only 20 references. To show more, press the button "Show all references".


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC14B.