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discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
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discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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MetaCyc Pathway: methylglyoxal degradation III

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 Aldehyde Degradation
Detoxification Methylglyoxal Detoxification

Some taxa known to possess this pathway include ? : Cyberlindnera mrakii , Escherichia coli K-12 substr. MG1655 , Homo sapiens , Mammalia , Synechococcus sp. PCC 7002 , Thermoanaerobacterium thermosaccharolyticum

Expected Taxonomic Range: Bacteria , Eukaryota

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

There are several pathways for the removal of methylglyoxal. In this pathway, methylglyoxal is reduced to acetol by the action of various enymes possessing L-glyceraldehyde 3-phosphate reductase activity. Most of the enzymes that have been characterized with this activity belong to the family of NADPH-dependent aldo-keto reductases (AKRs). For example, the human aldose reductase (EC 1.1.1.21) and aldehyde reductase (EC 1.1.1.2) are both capable of reducing methylglyoxal to acetol [Vander92]. Other mammalian AKRs that were shown to catalyze this reaction include AKR1, AKR1A, AKR1B1, AKR7, AKR7A2 and AKR7A5 [Wermuth77, Oconnor99, Hinshelwood02, Hinshelwood03].

Several Escherichia coli K-12 enzymes homologous to the mammalian AKRs have also been shown to catalyze the same reaction [Misra96]. Overexpression of the aldo-keto reductase AKR14A1, encoded by the yghZ gene, leads to increased resistance to methylglyoxal [Grant03a]. In addition, three other genes (yeaE, dkgA, and dkgB) were shown to encode proteins with similar activities [Ko05]. All four proteins were purified, and shown to catalyze the reaction in vitro, in the presence of NADPH. A similar enzyme has been identified in cyanobacteria [Xu06c].

A variation has been found in the Saccharomycete fungus Cyberlindnera mrakii, in which an NADH-dependent methylglyoxal reductase has been documented [Inoue92].

Prolonged incubations of Escherichia coli cell-free extracts with methylglyoxal resulted in conversion of acetol to (S)-propane-1,2-diol [Ko05]. The enzyme proposed to catalyze this reaction is L-1,2-propanediol dehydrogenase / glycerol dehydrogenase [Tang82, Kelley85]. A similar conversion has been observed in other microorganisms, such as Thermoanaerobacterium thermosaccharolyticum [Cameron86]. In bacteria (S)-propane-1,2-diol is a dead-end metabolite and exits the cell rapidly [Zhu89].

The same reaction has also been observed in mammalian systems, where it is catalyzed by aldose reductase [Vander92]. In mammals (S)-propane-1,2-diol is metabolized in the liver to L-lactate [Vander92].

Superpathways: superpathway of methylglyoxal degradation

Variants: methylglyoxal degradation I , methylglyoxal degradation II , methylglyoxal degradation IV , methylglyoxal degradation V , methylglyoxal degradation VI , methylglyoxal degradation VII , methylglyoxal degradation VIII

Unification Links: EcoCyc:PWY-5453

Credits:
Created 16-Jan-2007 by Caspi R , SRI International


References

Cameron86: Cameron, D.C., Cooney, C.L. (1986). "A novel fermentation: the production of (R)-1,2-propanediol and acetol by Clostridium thermosaccharolyticum." Nature Bio/Technology 4:651-654.

Grant03a: Grant AW, Steel G, Waugh H, Ellis EM (2003). "A novel aldo-keto reductase from Escherichia coli can increase resistance to methylglyoxal toxicity." FEMS Microbiol Lett 218(1);93-9. PMID: 12583903

Hinshelwood02: Hinshelwood A, McGarvie G, Ellis E (2002). "Characterisation of a novel mouse liver aldo-keto reductase AKR7A5." FEBS Lett 523(1-3);213-8. PMID: 12123834

Hinshelwood03: Hinshelwood A, McGarvie G, Ellis EM (2003). "Substrate specificity of mouse aldo-keto reductase AKR7A5." Chem Biol Interact 143-144;263-9. PMID: 12604212

Inoue92: Inoue, Y., Ikemoto, S., Kitamura, K., Kimura, A. (1992). "Occurrence of a NADH-dependent methylglyoxal reducing system: Conversion of methylglyoxal to acetol by aldehyde reductase from Hansenula mrakii." Journal of Fermentation and Bioengineering, 74(1): 46-48.

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

Kelley85: Kelley JJ, Dekker EE (1985). "Identity of Escherichia coli D-1-amino-2-propanol:NAD+ oxidoreductase with E. coli glycerol dehydrogenase but not with Neisseria gonorrhoeae 1,2-propanediol:NAD+ oxidoreductase." J Bacteriol 1985;162(1);170-5. PMID: 3920199

Ko05: Ko J, Kim I, Yoo S, Min B, Kim K, Park C (2005). "Conversion of methylglyoxal to acetol by Escherichia coli aldo-keto reductases." J Bacteriol 187(16);5782-9. PMID: 16077126

Misra96: Misra K, Banerjee AB, Ray S, Ray M (1996). "Reduction of methylglyoxal in Escherichia coli K12 by an aldehyde reductase and alcohol dehydrogenase." Mol Cell Biochem 156(2);117-24. PMID: 9095467

Oconnor99: O'connor T, Ireland LS, Harrison DJ, Hayes JD (1999). "Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members." Biochem J 343 Pt 2;487-504. PMID: 10510318

Tang82: Tang JC, Forage RG, Lin EC (1982). "Immunochemical properties of NAD+-linked glycerol dehydrogenases from Escherichia coli and Klebsiella pneumoniae." J Bacteriol 1982;152(3);1169-74. PMID: 6183251

Vander92: Vander Jagt DL, Robinson B, Taylor KK, Hunsaker LA (1992). "Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications." J Biol Chem 267(7);4364-9. PMID: 1537826

Wermuth77: Wermuth B, Munch JD, von Wartburg JP (1977). "Purification and properties of NADPH-dependent aldehyde reductase from human liver." J Biol Chem 252(11);3821-8. PMID: 16919

Xu06c: Xu D, Liu X, Guo C, Zhao J (2006). "Methylglyoxal detoxification by an aldo-keto reductase in the cyanobacterium Synechococcus sp. PCC 7002." Microbiology 152(Pt 7);2013-21. PMID: 16804176

Zhu89: Zhu Y, Lin EC (1989). "L-1,2-propanediol exits more rapidly than L-lactaldehyde from Escherichia coli." J Bacteriol 1989;171(2);862-7. PMID: 2644239

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

Asai96: Asai H, Imaoka S, Kuroki T, Monna T, Funae Y (1996). "Microsomal ethanol oxidizing system activity by human hepatic cytochrome P450s." J Pharmacol Exp Ther 277(2);1004-9. PMID: 8627510

Bohren89: Bohren KM, Bullock B, Wermuth B, Gabbay KH (1989). "The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases." J Biol Chem 264(16);9547-51. PMID: 2498333

Bondoc99: Bondoc FY, Bao Z, Hu WY, Gonzalez FJ, Wang Y, Yang CS, Hong JY (1999). "Acetone catabolism by cytochrome P450 2E1: studies with CYP2E1-null mice." Biochem Pharmacol 58(3);461-3. PMID: 10424765

Campbell73a: Campbell RL, Dekker EE (1973). "Formation of D-1-amino-2-propanol from L-threonine by enzymes from Escherichia coli K-12." Biochem Biophys Res Commun 53(2);432-8. PMID: 4577583

Campbell78: Campbell RL, Swain RR, Dekker EE (1978). "Purification, separation, and characterization of two molecular forms of D-1-amino-2-propanol:NAD+ oxidoreductase activity from extracts of Escherichia coli K-12." J Biol Chem 253(20);7282-8. PMID: 359547

Cintolesi12: Cintolesi A, Clomburg JM, Rigou V, Zygourakis K, Gonzalez R (2012). "Quantitative analysis of the fermentative metabolism of glycerol in Escherichia coli." Biotechnol Bioeng 109(1);187-98. PMID: 21858785

Desai08: Desai KK, Miller BG (2008). "A metabolic bypass of the triosephosphate isomerase reaction." Biochemistry 47(31);7983-5. PMID: 18620424

Dharmadi06: Dharmadi Y, Murarka A, Gonzalez R (2006). "Anaerobic fermentation of glycerol by Escherichia coli: a new platform for metabolic engineering." Biotechnol Bioeng 94(5);821-9. PMID: 16715533

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

diLuccio06: di Luccio E, Elling RA, Wilson DK (2006). "Identification of a novel NADH-specific aldo-keto reductase using sequence and structural homologies." Biochem J 400(1);105-14. PMID: 16813561

Durnin09: Durnin G, Clomburg J, Yeates Z, Alvarez PJ, Zygourakis K, Campbell P, Gonzalez R (2009). "Understanding and harnessing the microaerobic metabolism of glycerol in Escherichia coli." Biotechnol Bioeng 103(1);148-61. PMID: 19189409

Fairbrother98: Fairbrother KS, Grove J, de Waziers I, Steimel DT, Day CP, Crespi CL, Daly AK (1998). "Detection and characterization of novel polymorphisms in the CYP2E1 gene." Pharmacogenetics 8(6);543-52. PMID: 9918138

Gillam94: Gillam EM, Guo Z, Guengerich FP (1994). "Expression of modified human cytochrome P450 2E1 in Escherichia coli, purification, and spectral and catalytic properties." Arch Biochem Biophys 312(1);59-66. PMID: 8031147

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

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Gonzalez08: Gonzalez R, Murarka A, Dharmadi Y, Yazdani SS (2008). "A new model for the anaerobic fermentation of glycerol in enteric bacteria: trunk and auxiliary pathways in Escherichia coli." Metab Eng 10(5);234-45. PMID: 18632294

Guth80: Guth A, Engel R, Tropp BE (1980). "Uptake of glycerol 3-phosphate and some of its analogs by the hexose phosphate transport system of Escherichia coli." J Bacteriol 143(1);538-9. PMID: 6995450

Habrych02: Habrych M, Rodriguez S, Stewart JD (2002). "Purification and identification of an Escherichia coli beta-keto ester reductase as 2,5-diketo-D-gluconate reductase YqhE." Biotechnol Prog 18(2);257-61. PMID: 11934293

Hu97: Hu Y, Oscarson M, Johansson I, Yue QY, Dahl ML, Tabone M, Arinco S, Albano E, Ingelman-Sundberg M (1997). "Genetic polymorphism of human CYP2E1: characterization of two variant alleles." Mol Pharmacol 51(3);370-6. PMID: 9058590

Ioannides04: Ioannides C, Lewis DF (2004). "Cytochromes P450 in the bioactivation of chemicals." Curr Top Med Chem 4(16);1767-88. PMID: 15579107

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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 Fri Dec 19, 2014, biocyc14.