Glyoxalase system

The glyoxalase system is a set of enzymes that carry out the detoxification of methylglyoxal and the other reactive aldehydes that are produced as a normal part of metabolism. [Vander Jagt, D. (1989). "The glyoxalase system". In Glutathione: Chemical, Biochemical and Medical Aspects. Part A, D. Dolphin, R. Poulson, and O. Avramovic, eds. (New York: John Wiley & Sons), pp. 597-641.] This system has been studies in both bacteria and eukaryotes. [cite journal |author=Dixon DP, Cummins L, Cole DJ, Edwards R |title=Glutathione-mediated detoxification systems in plants |journal=Curr. Opin. Plant Biol. |volume=1 |issue=3 |pages=258–66 |year=1998 |pmid=10066594 |doi=10.1016/S1369-5266(98)80114-3] [cite journal |author=Inoue Y, Kimura A |title=Methylglyoxal and regulation of its metabolism in microorganisms |journal=Adv. Microb. Physiol. |volume=37 |issue= |pages=177–227 |year=1995 |pmid=8540421]

This detoxification is accomplished by the sequential action of two thiol-dependent enzymes; firstly glyoxalase І, which catalyses the isomerisation of the spontaneously formed hemithioacetal adduct between GSH and 2-oxoaldehydes (such as methylglyoxal) into S-2-hydroxyacylglutathione. [cite journal |author=Thornalley PJ |title=Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation |journal=Biochem. Soc. Trans. |volume=31 |issue=Pt 6 |pages=1343–8 |year=2003 |pmid=14641060 |url=http://www.biochemsoctrans.org/bst/031/1343/bst0311343.htm] [cite journal |author=Creighton DJ, Hamilton DS |title=Brief history of glyoxalase I and what we have learned about metal ion-dependent, enzyme-catalyzed isomerizations |journal=Arch. Biochem. Biophys. |volume=387 |issue=1 |pages=1–10 |year=2001 |pmid=11368170 |doi=10.1006/abbi.2000.2253] Secondly, glyoxalase ІІ hydrolyses these thiolesters and in the case of methylglyoxal catabolism, produces D-lactate and GSH from S-D-lactoyl-glutathione. [cite journal |author=Vander Jagt DL |title=Glyoxalase II: molecular characteristics, kinetics and mechanism |journal=Biochem. Soc. Trans. |volume=21 |issue=2 |pages=522–7 |year=1993 |pmid=8359524]

This system shows many of the typical features of the enzymes that dispose of endogenous toxins. Firstly, in contrast to the amazing substrate range of many of the enzymes involved in xenobiotic metabolism, it shows a narrow substrate specificity. Secondly, intracellular thiols are required as part of its enzymatic mechanism and thirdly, the system acts to recycle reactive metabolites back to a form which may be useful to cellular metabolism.

ee also

*Antioxidant
*Advanced glycation endproduct

References


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