Glutathione mutagenesis in Salmonella typhimurium TA100: dependence on a single enzyme, gamma-glutamyltranspeptidase.
Glutathione was mutagenic in Salmonella typhimurium strain TA100 in the presence of purified mammalian gamma-glutamyltranspeptidase. Glutathione disulfide, gamma-glutamyl glutamic acid, and S-methyl-glutathione were not mutagenic under the same conditions. Glutathione-mediated, gamma-glutamyltranspeptidase-dependent mutagenesis of TA100 cells was inhibited by serine-borate complex, a known gamma-glutamyltranspeptidase inhibitor, and potentiated by glycylglycine, a known gamma-glutamyltranspeptidase enhancer. It is concluded that this enzyme is necessary and sufficient to activate glutathione to a mutagen.
D000818:Animals; D001711:Biotransformation; D001881:Borates / Q000494:pharmacology; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology*; D006033:Glycylglycine / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects*; D012694:Serine / Q000494:pharmacology; D013552:Swine; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001881:Borates; C040900:serine-borate complex; D006033:Glycylglycine; D012694:Serine; D005723:gamma-Glutamyltransferase; D005978:Glutathione