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Escherichia coli K-12 substr. MG1655 Pathway: methylglyoxal degradation I

Pathway diagram: methylglyoxal degradation I

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

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic: ?

Genetic regulation schematic for methylglyoxal degradation I

Superclasses: Degradation/Utilization/Assimilation Aldehyde Degradation
Detoxification Methylglyoxal Detoxification

Summary:
General Background

Methylglyoxal is produced in small amounts during glycolysis (via dihydroxyacetone phosphate), fatty acid metabolism (via acetone) and protein metabolism (via aminoacetone). Methylglyoxal is highly toxic, most likely as a result of its interaction with protein side chains (see [Kalapos99] for a review). There are several pathways for the detoxification of methylglyoxal, based on different enzymes that are able to convert methylglyoxal to less toxic compounds. These enzymes include glyoxalase enzymes, methylglyoxal reductases, aldose reductases, aldehyde reductases and methylglyoxal dehydrogenases.

About This Pathway

In E. coli, the glutathione-dependent glyoxalase system is probably the most common pathway that catalyzes the conversion of methylglyoxal to a less toxic product. In the pathway shown here, methylglyoxal is converted to (R)-lactate via the intermediate (S)-lactoyl-glutathione by two glyoxylase enzymes. glyoxalase I (GloA) isomerizes the hemithioacetal that is formed non-enzymatically from methylglyoxal and glutathione to (S)-lactoyl-glutathione. Glyoxalase II enzymes, mainly GloB with a minor contribution from GloC, hydrolyze the thioester to (R)-lactate, regenerating the glutathione in the process [Reiger15]. In addition, YeiG can catalyze the hydrolysis of S-lactoylglutathione and may also be involved in the detoxification of endogenous methylglyoxal [Gonzalez06a].

This system not only involves the enzymes encoded by the unlinked genes gloA, gloB and gloC, but also their integration with the glutathione adduct-gated KefGB K+ efflux system. Studies of a ΔgloB mutant supported a model that includes activation of KefGB by S-lactoylglutathione resulting in K+ efflux and H+ influx. This lowering of cytoplasmic pH also protects against methylglyoxal damage [Ozyamak10].

The fate of (R)-lactate is less well characterized. It can be excreted or further metabolized [Ozyamak10]. In the latter case it may be converted to pyruvate by the action of D-lactate dehydrogenase, a flavoprotein specific to the D-form of lactate [Dym00].

Reviews: [Kalapos99], and Booth, I.R. (2005) Glycerol and Methylglyoxal Metabolism, Module 3.4.3 in [ECOSAL]

Superpathways: superpathway of methylglyoxal degradation

Variants: methylglyoxal degradation II , methylglyoxal degradation III , methylglyoxal degradation IV

Credits:
Created 24-Oct-2006 by Caspi R , SRI International
Revised 27-Mar-2015 by Keseler I , SRI International
Last-Curated ? 14-Feb-2013 by Fulcher C , SRI International


References

Dym00: Dym O, Pratt EA, Ho C, Eisenberg D (2000). "The crystal structure of D-lactate dehydrogenase, a peripheral membrane respiratory enzyme." Proc Natl Acad Sci U S A 97(17);9413-8. PMID: 10944213

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

Gonzalez06a: Gonzalez CF, Proudfoot M, Brown G, Korniyenko Y, Mori H, Savchenko AV, Yakunin AF (2006). "Molecular basis of formaldehyde detoxification: Characterization of two s-formylglutathione hydrolases from Escherichia coli, FrmB and YeiG." J Biol Chem 281:14514-14522. PMID: 16567800

Kalapos99: Kalapos MP (1999). "Methylglyoxal in living organisms: chemistry, biochemistry, toxicology and biological implications." Toxicol Lett 110(3);145-75. PMID: 10597025

Ozyamak10: Ozyamak E, Black SS, Walker CA, Maclean MJ, Bartlett W, Miller S, Booth IR (2010). "The critical role of S-lactoylglutathione formation during methylglyoxal detoxification in Escherichia coli." Mol Microbiol 78(6);1577-90. PMID: 21143325

Reiger15: Reiger M, Lassak J, Jung K (2015). "Deciphering the role of the type II glyoxalase isoenzyme YcbL (GlxII-2) in Escherichia coli." FEMS Microbiol Lett 362(2);1-7. PMID: 25670698

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

Barnes70: Barnes EM, Kaback HR (1970). "Beta-galactoside transport in bacterial membrane preparations: energy coupling via membrane-bounded D-lactic dehydrogenase." Proc Natl Acad Sci U S A 66(4);1190-8. PMID: 4394455

Barnes71: Barnes EM, Kaback HR (1971). "Mechanisms of active transport in isolated membrane vesicles. I. The site of energy coupling between D-lactic dehydrogenase and beta-galactoside transport in Escherichia coli membrane vesicles." J Biol Chem 1971;246(17);5518-22. PMID: 4330922

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

Campbell84: Campbell HD, Rogers BL, Young IG (1984). "Nucleotide sequence of the respiratory D-lactate dehydrogenase gene of Escherichia coli." Eur J Biochem 144(2);367-73. PMID: 6386470

CamposBermudez10a: Campos-Bermudez VA, Gonzalez JM, Tierney DL, Vila AJ (2010). "Spectroscopic signature of a ubiquitous metal binding site in the metallo-β-lactamase superfamily." J Biol Inorg Chem 15(8);1209-18. PMID: 20535505

Clugston04: Clugston SL, Yajima R, Honek JF (2004). "Investigation of metal binding and activation of Escherichia coli glyoxalase I: kinetic, thermodynamic and mutagenesis studies." Biochem J 377(Pt 2);309-16. PMID: 14556652

Clugston98: Clugston SL, Barnard JF, Kinach R, Miedema D, Ruman R, Daub E, Honek JF (1998). "Overproduction and characterization of a dimeric non-zinc glyoxalase I from Escherichia coli: evidence for optimal activation by nickel ions." Biochemistry 1998;37(24);8754-63. PMID: 9628737

Davidson00: Davidson G, Clugston SL, Honek JF, Maroney MJ (2000). "XAS investigation of the nickel active site structure in Escherichia coli glyoxalase I." Inorg Chem 39(14);2962-3. PMID: 11196887

Davidson01: Davidson G, Clugston SL, Honek JF, Maroney MJ (2001). "An XAS investigation of product and inhibitor complexes of Ni-containing GlxI from Escherichia coli: mechanistic implications." Biochemistry 40(15);4569-82. PMID: 11294624

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

Fung79: Fung LW, Pratt EA, Ho C (1979). "Biochemical and biophysical studies on the interaction of a membrane-bound enzyme, D-lactate dehydrogenase from Escherichia coli, with phospholipids." Biochemistry 1979;18(2);317-24. PMID: 369600

Futai73: Futai M (1973). "Membrane D-lactate dehydrogenase from Escherichia coli. Purification and properties." Biochemistry 12(13);2468-74. PMID: 4575624

GeorgeNasciment76: George-Nascimento C, Wakil SJ, Short SA, Kaback HR (1976). "Effect of lipids on the reconstitution of D-lactate oxidase in Escherichia coli membrane vesicles." J Biol Chem 251(21);6662-6. PMID: 789373

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Harold74: Harold FM (1974). "Chemiosmotic interpretation of active transport in bacteria." Ann N Y Acad Sci 227;297-311. PMID: 4275121

Haugaard59: Haugaard N (1959). "D- and L-lactic acid oxidases of Escherichia coli." Biochim Biophys Acta 31(1);66-72. PMID: 13628604

Hayashi13: Hayashi M, Tabata K (2013). "Metabolic engineering for L-glutamine overproduction by using DNA gyrase mutations in Escherichia coli." Appl Environ Microbiol 79(9);3033-9. PMID: 23455340

He00: He MM, Clugston SL, Honek JF, Matthews BW (2000). "Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation." Biochemistry 39(30);8719-27. PMID: 10913283

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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 19.0 on Wed Sep 2, 2015, biocyc11.