Subsystem: Glutathione: Non-redox reactions
This subsystem's description is:
Three groups of glutathione-dependent enzymes are included in this Subsystem:
- Glutathione S-transferases - major phase II detoxification enzymes;
- Glyoxalases I and II of the glutathione-dependent pathway of methylglyoxal detoxification;
- Phytochelatin synthases - key enzymes for heavy-metal detoxification in plants (and some prokaryotes)
I. The glutathione transferases (also known as glutathione S-transferases) are major phase II detoxification enzymes. In addition to their role in catalyzing the conjugation of electrophilic substrates to glutathione (GSH), these enzymes also carry out a range of other functions. They have peroxidase and isomerase activities, and can bind non-catalytically a wide range of endogenous and exogenous ligands. Cytosolic GSTs of mammals have been particularly well characterized, and were originally classified into Alpha, Mu, Pi and Theta classes. Currently the GST superfamily is being subdivided further into an ever-increasing number of classes based on a variety of criteria, including amino acid\nucleotide sequence, and immunological, kinetic and tertiary\quaternary structural properties. Moreover, several novel classes identified in non-mammalian species have been subsequently identified in mammals, sometimes carrying out functions not previously associated with GSTs. For example, Zeta-class GST was determined to be identical with maleylacetate isomerase, an enzyme of the catabolic pathway for tyrosine
II. Lactoylglutathione lyase (EC 188.8.131.52) and Hydroxyacylglutathione hydrolase (EC 184.108.40.206) (also called glyoxalase I and glyoxalase II) catalyze the two sequential reactions of the glutathione-dependent pathway of methylglyoxal detoxification. Glyoxalase I is a metalloisomerase that converts the non-enzymically formed Methylglyoxal–GSH hemithioacetal adduct into the corresponding thioester. This product is subsequently hydrolysed by glyoxalase II, generating D-lactate and regenerating GSH. See Subsystem "Methylglyoxal_Metabolism" for details. Notably, two characterized SAM-dependent methyltransferase protein families cluster tightly with glyoxalase II in the majority of microorganisms
III. Phytochelatins (PCs) are known to be the main heavy-metal- detoxifying peptides in the plant kingdom (1). PCs are glutathione (GSH)-derived peptides of the general formula (gamma-Glu-Cys)nGly (with n= 2–11), which have been identified in a wide variety of plant species and in some microorganisms. They act as heavy metal (mainly Cd2+chelators and favor their vacuolar sequestration.
PCs are synthesized posttranslationally in the presence of heavy-metal ions by the PC synthase, a gamma-glutamyl-cysteine transpeptidase. This enzyme can also hydrolyze GSH and GS-conjugated xenobiotics. Genes encoding PCS have been isolated and characterized in Arabidopsis thaliana (AtPCS1), Schizosaccharomyces pombe (SpPCS), and wheat (Triticum aestivum; TaPCS1), but also in the model nematode Caenorhabditis elegans (CePCS1) and cyanobacteria (Rea, 2006; Vivares et al., 2005: Harada, et al., 2004). In the cyanobacterium Nostoc, the enzyme (NsPCS) contains only the catalytic domain of the eukaryotic synthase and can act as a GSH hydrolase and weakly as a peptide ligase.
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