S-Transferase

Glutathione S-transferase M1 Deficient activity in about 50% of Caucasians. Carriers of the deficiency may have a slightly increased risk for a number of smoking-related cancers. 

MotoyamaN, Dauterman WC. 1978. Multiple forms of rat liver glutathione S-transferases Specificity for conjugation of 0-alkyl and 0-aryl groups of organophosphorus insecticides. J Agr Food Chem 26 1296-1301. 

Polidoro G, Dillio C, Arduini A, et al. 1982. Glutathione peroxidase and glutathione S-transferase activities in human fetal tissues. Inability of acidic forms of glutathione S-transferase to catalyze the reduction of organic hydroperoxides. Biochem Int 4 637-645. 

Radulovic LL, Kulkami AP, Dauterman WC. 1987. Biotransformation of methyl parathion by human foetal liver glutathione S-transferases An in vitro study. Xenobiotic 17 105-114. 

Radulovic LL, Laferla JJ, Kulkami AP. 1986. Human placental glutathione S-transferase-mediated metabolism of methyl parathion. Biochem pharmacol 35 3473-3480. 

Dwivedi PP, Mishra A, Dutta KK. 1988. Studies of endosulfan on glutathione, glutathione-S-transferase and total sulfhydryls in rat liver. Agricultural and Biological Research 4 18-21. 

Narayan S, Bajpai A, Tyagi SR, et al. 1985b. Effect of intratracheal administration of DDT and endosulfan on cytochrome P-450 and glutathione-s-transferase in lung and liver of rats. Bull Environ Contam Toxicol 34 55-62. 

A nnmber of other examples are known in which genetically based resistance was dne to enhanced detoxication of OPs. These include malathion resistance in some stored product pests owing to high carboxylesterase activity, and resistance of strains of the housefly to diazinon due to detoxication by specific forms of a glutathione-S-transferase and monooxygenase (Brooks 1972). 

Glutathione-S-transferases A group of enzymes that catalyze the formation of conjugates between reduced glutathione and xenobiotics. 

Soffers AEMF, Ploeman JHTM, Moonen MJH, Wobbes T, van Ommen B, Vervoort J, et al. Regioselectivity and quantitative structure-activity relationships for the conjugation of a series of fluoronitrobenzenes by purified glutathione S -transferase enzymes from rat and man. Chem Res Toxicol 1996 9 638-46. 

Figure 7-12. Use of glutathione S-transferase (GST) fusion proteins to purify recombinant proteins. (GSH, glutathione.)...

Figure 23-7. Conversion of arachidonicacid to leukotrienesand lipoxins of series 4 via the lipoxygenase pathway. Some similar conversions occur in series 3 and 5 leukotrienes. (HPETE, hydroperoxyeicosatetraenoate HETE, hydroxyeicosatetraenoate , peroxidase (2), leukotriene A4 epoxide hydrolase , glutathione S-transferase ...

Once bilirubin enters the hepatocytes, it can bind to certain cytosolic proteins, which help to keep it solubilized prior to conjugation. Ligandin (a family of glutathione S-transferases) and protein Y are the involved proteins. They may also help to prevent efflux of bilirubin back into the blood stream. 

Figure 32-15. Diagrammatic representation of the three major processes (uptake, conjugation, and secretion) involved in the transfer of bilirubin from blood to bile. Certain proteins of hepatocytes, such as ligandin (a family of glutathione S-transferase) and Y protein, bind intracellular bilirubin and may prevent its efflux into the blood stream. The process affected in a number of conditions causing jaundice is also shown.

Figure 53-1. Simplified scheme showing how metabolism of a xenobiotic can result in cell injury, immunologic damage, or cancer. In this instance, the conversion of the xenobiotic to a reactive metabolite is catalyzed by a cytochrome P450,and the conversion of the reactive metabolite (eg, an epoxide) to a nontoxic metabolite is catalyzed either by a GSH S-transferase or by epoxide hydrolase.

Dekant W, Martens G, Vamvakas S, et al. 1987. Bioactivation of tetrachloroethylene. Role of glutathione S-transferase-catalyzed conjugation versus cytochrome P-450-dependent phospholipid alkylation. Drug Metab Dispos Biol Fate Chem 15 702-709. 

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