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|
Methylglyoxal is produced in small amounts during glycolysis (via glycerone 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 18.104.22.168) and aldehyde reductase (EC 22.214.171.124) 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 [Xu06a].
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
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
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.
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
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
Atsumi10: Atsumi S, Wu TY, Eckl EM, Hawkins SD, Buelter T, Liao JC (2010). "Engineering the isobutanol biosynthetic pathway in Escherichia coli by comparison of three aldehyde reductase/alcohol dehydrogenase genes." Appl Microbiol Biotechnol 85(3);651-7. PMID: 19609521
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
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
Dellomonaco11: Dellomonaco C, Clomburg JM, Miller EN, Gonzalez R (2011). "Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals." Nature 476(7360);355-9. PMID: 21832992
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
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
Foo14: Foo JL, Jensen HM, Dahl RH, George K, Keasling JD, Lee TS, Leong S, Mukhopadhyay A (2014). "Improving microbial biogasoline production in Escherichia coli using tolerance engineering." MBio 5(6);e01932. PMID: 25370492
Geddes14: Geddes RD, Wang X, Yomano LP, Miller EN, Zheng H, Shanmugam KT, Ingram LO (2014). "Polyamine transporters and polyamines increase furfural tolerance during xylose fermentation with ethanologenic Escherichia coli strain LY180." Appl Environ Microbiol 80(19);5955-64. PMID: 25063650
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
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