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MetaCyc Pathway: 2-oxoglutarate decarboxylation to succinyl-CoA

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: 2-oxoglutarate dehydrogenase complex, 2-ketoglutarate dehydrogenase complex

Superclasses: Degradation/Utilization/Assimilation Amino Acids Degradation
Generation of Precursor Metabolites and Energy Respiration

Some taxa known to possess this pathway include ? : Bacillus subtilis , Deinococcus radiodurans , Escherichia coli K-12 substr. MG1655 , Geobacillus stearothermophilus , Homo sapiens , Mus musculus , Pseudomonas aeruginosa , Pseudomonas putida , Rattus norvegicus , Sulfolobus solfataricus , Synechocystis

Expected Taxonomic Range: Archaea , Bacteria , Eukaryota

Summary:
General Background

2-oxo acid dehydrogenase complexes convert 2-oxo acids to the corresponding acyl-CoA derivatives and produce NADH and CO2 in an irreversible reaction. Five members of this family are known at present, including the pyruvate dehydrogenase complex (PDHC), the 2-oxoglutarate dehydrogenase complex (OGDHC - this pathway), the branched-chain α-keto acid dehydrogenase complex (BCDHC), the glycine cleavage complex (GDHC), and the acetoin dehydrogenase complex (ADHC). They all function at strategic points in (usually aerobic) catabolic pathways and are subject to stringent control [deKok98].

With the exception of GDHC, the 2-oxo acid dehydrogenase complexes share a common structure. They consist of three main components, namely a 2-oxo acid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). In Gram-positive bacteria and mitochondria, the E1 component is a heterodimer composed of two subunits, while in Gram-negative bacteria it is made of a single type of subunit.

In all cases described so far, many copies of each subunit assemble to form the full complex. For example, the Escherichia coli K-12 pyruvate dehydrogenase comprises 24, 24, and 12 units of the E1, E2, and E3 components, respectively. The core of the complex is made of either 24 (Gram-negative bacteria) or 60 (mitochondria) E2 units, which contain the lipoyl active site in the form of lipoyllysine, as well as binding sites for the other two subunits. E1, which contains a thiamin diphosphate cofactor, catalyzes the binding of the 2-oxo acid to the lipoyl group of E2, which then transfers an acyl group (the nature of the acyl group depends on the particular enzyme) to coenzyme A, forming an acyl-CoA. During this transfer, the lipoyl group is reduced to dihydrolipoyl. E3 then transfers the protons to NAD, forming NADH and restoring the dihydrolipoyllysine group back to lipoyllysine.

Cryoelectron microscopy of PDHC from Geobacillus stearothermophilus [Milne02] and ox kidney [Zhou01] has revealed that the E2 inner core is surrounded by an outer shell of E1 and E3 components, with the lipoyl domains confined to the annular space between them where they must make successive journeys between the three types of active sites (E1-E3), which are physically far apart [Fries03].

About This Pathway

The pathway illustrated here presents the reactions catalyzed by the 2-oxoglutarate dehydrogenase complex, a key enzyme of the TCA cycle I (prokaryotic). These reactions can be summarized by the general reaction

2-oxoglutarate + coenzyme A + NAD+ → succinyl-CoA + CO2 + NADH

which is the form commonly found in the TCA cycle.

Unification Links: EcoCyc:PWY-5084

Credits:
Created 16-Jan-2006 by Caspi R , SRI International


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

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

Zhou01: Zhou ZH, McCarthy DB, O'Connor CM, Reed LJ, Stoops JK (2001). "The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes." Proc Natl Acad Sci U S A 98(26);14802-7. PMID: 11752427

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

Ali94: Ali G, Wasco W, Cai X, Szabo P, Sheu KF, Cooper AJ, Gaston SM, Gusella JF, Tanzi RE, Blass JP (1994). "Isolation, characterization, and mapping of gene encoding dihydrolipoyl succinyltransferase (E2k) of human alpha-ketoglutarate dehydrogenase complex." Somat Cell Mol Genet 20(2);99-105. PMID: 8009371

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

Ambrus09: Ambrus A, Torocsik B, Adam-Vizi V (2009). "Periplasmic cold expression and one-step purification of human dihydrolipoamide dehydrogenase." Protein Expr Purif 63(1);50-7. PMID: 18845259

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

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

Brown02a: Brown RM, Head RA, Brown GK (2002). "Pyruvate dehydrogenase E3 binding protein deficiency." Hum Genet 110(2);187-91. PMID: 11935326

Bryk02: Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C (2002). "Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein." Science 295(5557);1073-7. PMID: 11799204

Buck85: Buck D, Spencer ME, Guest JR (1985). "Primary structure of the succinyl-CoA synthetase of Escherichia coli." Biochemistry 24(22);6245-52. PMID: 3002435

Buck86: Buck D, Spencer ME, Guest JR (1986). "Cloning and expression of the succinyl-CoA synthetase genes of Escherichia coli K12." J Gen Microbiol 1986;132 ( Pt 6);1753-62. PMID: 3543212

Bunik08: Bunik VI, Degtyarev D (2008). "Structure-function relationships in the 2-oxo acid dehydrogenase family: substrate-specific signatures and functional predictions for the 2-oxoglutarate dehydrogenase-like proteins." Proteins 71(2);874-90. PMID: 18004749

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

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

Cunningham98: Cunningham L, Guest JR (1998). "Transcription and transcript processing in the sdhCDAB-sucABCD operon of Escherichia coli." Microbiology 144 ( Pt 8);2113-23. PMID: 9720032

Darlison84b: Darlison MG, Spencer ME, Guest JR (1984). "Nucleotide sequence of the sucA gene encoding the 2-oxoglutarate dehydrogenase of Escherichia coli K-12." Eur J Biochem. 141(2):351-9. PMID: 6376123

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

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

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

Feigenbaum93: Feigenbaum AS, Robinson BH (1993). "The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements." Genomics 17(2);376-81. PMID: 8406489

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 MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Nov 20, 2014, BIOCYC14B.