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MetaCyc Pathway: 2-methylcitrate cycle I

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.

Superclasses: Degradation/Utilization/Assimilation Carboxylates Degradation Propionate Degradation 2-Methylcitrate Cycle

Some taxa known to possess this pathway include ? : Escherichia coli K-12 substr. MG1655 , Salmonella enterica enterica serovar Typhimurium , Yarrowia lipolytica

Expected Taxonomic Range: Bacteria , Fungi

Summary:
Propionate can have broad negative effects on the bacterial cell functions, including cytosol acidification, dissipation of the proton motive force, disruption of CoA homeostasis, and, in some cases, inhibition of the key TCA enzymes aconitase and citrate synthase due to formation of (2S,3S)-2-methylcitrate. For these reasons propionate is sometimes used as a preservative in foods. However, some bacteria are able to degrade propionate, and even use it the sole carbon source. Out of all the propionate degradation pathways, the 2-methylcitric acid cycle is the most widely destributed. In this pathway, the Cα methylene group of propionate is oxidized to a keto group yielding pyruvate, a common precursor for biosynthesis and energy production.

The pathway, which was discovered in fungi [Tabuchi74] was best characterized in Salmonella enterica enterica serovar Typhimurium [Horswill99a, Horswill01]. In that organism the pathway begins with the activation of propanoate to propanoyl-CoA by propionate-CoA ligase, followed by the synthesis of (2S,3S)-2-methylcitrate from propanoyl-CoA and oxaloacetate, catalyzed by 2-methylcitrate synthase. (2S,3S)-2-methylcitrate is then dehydrated to cis-2-methylaconitate by 2-methylcitrate dehydratase, followed by rehydration to (2R,3S)-2-methylisocitrate (catalyzed by aconitate hydratase 1 and aconitate hydratase 2) and cleavage of the later into pyruvate and succinate, performed by 2-methylisocitrate lyase. As mentioned above, pyruvate is a common precursor for biosynthesis and energy production.

Biochemical experiments have shown that Escherichia coli oxidizes propionate via the methylcitrate cycle [Brock02, London99, Textor97]. This pathway has been studied in vitro [Brock02]. Acs appears to be more likely than PrpE to catalyze the first step in the propionate metabolism pathway [Brock02]. The prpD gene encodes 2-methylcitrate dehydratase activity [Blank02] and also encodes the minor aconitase activity, aconitase C [Blank02], which constitutes 5% or less of cellular activity and is observed in an acnA acnB double mutant [Gruer97].

Even though the pathway is depicted as linear in MetaCyc, it is considered a cycle since oxaloacetate can be regenerated from succinate via enzymes of the TCA cycle I (prokaryotic) [Horswill99a].

Some organisms do not have the enzyme 2-methylcitrate dehydratase. These organisms have a different version of the pathway, which is described in 2-methylcitrate cycle II.

Variants: 2-methylcitrate cycle II

Unification Links: EcoCyc:PWY0-42

Credits:
Created 20-Jun-2000 by Pellegrini-Toole A , Marine Biological Laboratory
Revised 11-Dec-2007 by Caspi R , SRI International


References

Blank02: Blank L, Green J, Guest JR (2002). "AcnC of Escherichia coli is a 2-methylcitrate dehydratase (PrpD) that can use citrate and isocitrate as substrates." Microbiology 148(Pt 1);133-46. PMID: 11782506

Brock02: Brock M, Maerker C, Schutz A, Volker U, Buckel W (2002). "Oxidation of propionate to pyruvate in Escherichia coli. Involvement of methylcitrate dehydratase and aconitase." Eur J Biochem 269(24);6184-94. PMID: 12473114

Gruer97: Gruer MJ, Bradbury AJ, Guest JR (1997). "Construction and properties of aconitase mutants of Escherichia coli." Microbiology 143 ( Pt 6);1837-46. PMID: 9202458

Horswill01: Horswill AR, Escalante-Semerena JC (2001). "In vitro conversion of propionate to pyruvate by Salmonella enterica enzymes: 2-methylcitrate dehydratase (PrpD) and aconitase Enzymes catalyze the conversion of 2-methylcitrate to 2-methylisocitrate." Biochemistry 40(15);4703-13. PMID: 11294638

Horswill99a: Horswill AR, Escalante-Semerena JC (1999). "Salmonella typhimurium LT2 catabolizes propionate via the 2-methylcitric acid cycle." J Bacteriol 181(18);5615-23. PMID: 10482501

London99: London RE, Allen DL, Gabel SA, DeRose EF (1999). "Carbon-13 nuclear magnetic resonance study of metabolism of propionate by Escherichia coli." J Bacteriol 1999;181(11);3562-70. PMID: 10348870

Tabuchi74: Tabuchi, T., Hara, S. (1974). "Production of 2-methylisocitric acid from N-paraffins by mutants of candida-lipolytica." Agric. Biol. Chem. 38:1105-1106.

Textor97: Textor S, Wendisch VF, De Graaf AA, Muller U, Linder MI, Linder D, Buckel W (1997). "Propionate oxidation in Escherichia coli: evidence for operation of a methylcitrate cycle in bacteria." Arch Microbiol 1997;168(5);428-36. PMID: 9325432

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

Armando12: Armando JW, Boghigian BA, Pfeifer BA (2012). "LC-MS/MS quantification of short-chain acyl-CoA's in Escherichia coli demonstrates versatile propionyl-CoA synthetase substrate specificity." Lett Appl Microbiol 54(2);140-8. PMID: 22118660

Barak01: Barak R, Eisenbach M (2001). "Acetylation of the response regulator, CheY, is involved in bacterial chemotaxis." Mol Microbiol 40(3);731-43. PMID: 11359578

Barak04: Barak R, Eisenbach M (2004). "Co-regulation of acetylation and phosphorylation of CheY, a response regulator in chemotaxis of Escherichia coli." J Mol Biol 342(2);375-81. PMID: 15327941

Barak04a: Barak R, Prasad K, Shainskaya A, Wolfe AJ, Eisenbach M (2004). "Acetylation of the chemotaxis response regulator CheY by acetyl-CoA synthetase purified from Escherichia coli." J Mol Biol 342(2);383-401. PMID: 15327942

Barak06: Barak R, Yan J, Shainskaya A, Eisenbach M (2006). "The chemotaxis response regulator CheY can catalyze its own acetylation." J Mol Biol 359(2);251-65. PMID: 16630631

Barak92: Barak R, Welch M, Yanovsky A, Oosawa K, Eisenbach M (1992). "Acetyladenylate or its derivative acetylates the chemotaxis protein CheY in vitro and increases its activity at the flagellar switch." Biochemistry 31(41);10099-107. PMID: 1390767

Barak98: Barak R, Abouhamad WN, Eisenbach M (1998). "Both acetate kinase and acetyl coenzyme A synthetase are involved in acetate-stimulated change in the direction of flagellar rotation in Escherichia coli." J Bacteriol 1998;180(4);985-8. PMID: 9473056

Bradbury96: Bradbury AJ, Gruer MJ, Rudd KE, Guest JR (1996). "The second aconitase (AcnB) of Escherichia coli." Microbiology 142 ( Pt 2);389-400. PMID: 8932712

Bramer01: Bramer CO, Steinbuchel A (2001). "The methylcitric acid pathway in Ralstonia eutropha: new genes identified involved in propionate metabolism." Microbiology 147(Pt 8);2203-14. PMID: 11495997

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

Brock01: Brock M, Darley D, Textor S, Buckel W (2001). "2-Methylisocitrate lyases from the bacterium Escherichia coli and the filamentous fungus Aspergillus nidulans: characterization and comparison of both enzymes." Eur J Biochem 268(12);3577-86. PMID: 11422389

Brown77: Brown TD, Jones-Mortimer MC, Kornberg HL (1977). "The enzymic interconversion of acetate and acetyl-coenzyme A in Escherichia coli." J Gen Microbiol 1977;102(2);327-36. PMID: 21941

Calderon09: Calderon IL, Elias AO, Fuentes EL, Pradenas GA, Castro ME, Arenas FA, Perez JM, Vasquez CC (2009). "Tellurite-mediated disabling of [4Fe-4S] clusters of Escherichia coli dehydratases." Microbiology 155(Pt 6);1840-6. PMID: 19383690

Canovas03: Canovas M, Bernal V, Torroglosa T, Ramirez JL, Iborra JL (2003). "Link between primary and secondary metabolism in the biotransformation of trimethylammonium compounds by escherichia coli." Biotechnol Bioeng 84(6);686-99. PMID: 14595781

CastanoCerezo09: Castano-Cerezo S, Pastor JM, Renilla S, Bernal V, Iborra JL, Canovas M (2009). "An insight into the role of phosphotransacetylase (pta) and the acetate/acetyl-CoA node in Escherichia coli." Microb Cell Fact 8;54. PMID: 19852855

CastanoCerezo11: Castano-Cerezo S, Bernal V, Blanco-Catala J, Iborra JL, Canovas M (2011). "cAMP-CRP co-ordinates the expression of the protein acetylation pathway with central metabolism in Escherichia coli." Mol Microbiol 82(5);1110-28. PMID: 22059728

Cunningham97: Cunningham L, Gruer MJ, Guest JR (1997). "Transcriptional regulation of the aconitase genes (acnA and acnB) of Escherichia coli." Microbiology 143 ( Pt 12);3795-805. PMID: 9421904

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

Gerike98: Gerike U, Hough DW, Russell NJ, Dyall-Smith ML, Danson MJ (1998). "Citrate synthase and 2-methylcitrate synthase: structural, functional and evolutionary relationships." Microbiology 1998;144 ( Pt 4);929-35. PMID: 9579066

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

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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 Sun Nov 23, 2014, biocyc13.