title: Glutathione metabolism by gamma-glutamyltranspeptidase leads to lipid peroxidation: characterization of the system and relevance to hepatocarcinogenesis.
abstract: Glutathione (GSH)-driven lipid peroxidation (LPO) in vitro was catalyzed by gamma-glutamyltranspeptidase (GGT; EC 2.3.2.2.). The reaction required iron, iron chelators and oxygen, was accelerated by glycylglycine (gly)2, a GGT enhancer, and was inhibited by the GGT inhibitors serine--borate and acivicin. LPO occurred at rat plasma concentrations of GSH and transferrin, and in the presence of putative physiological chelators such as citrate and ADP. GSH-driven LPO was inhibited by butylated hydroxytoluene, but not by catalase, peroxidase or superoxide dismutase. These results suggest that metabolism of GSH initiated by GGT may lead to oxidative damage. Such oxidative damage may be induced in vivo by GSH in proximity to GGT-rich preneoplastic foci in rat liver.
authors.affiliation: Department of Biochemistry, Tel-Aviv University, Ramat-Aviv, Israel.
authors.forename: A A
authors.initials: AA
authors.lastname: Stark
authors.forename: E
authors.initials: E
authors.lastname: Zeiger
authors.forename: D A
authors.initials: DA
authors.lastname: Pagano
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D016166:Free Radical Scavengers; D005978:Glutathione / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000209:etiology* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011230:Precancerous Conditions / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism; D051381:Rats; D014168:Transferrin / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; D016166:Free Radical Scavengers; D014168:Transferrin; D007501:Iron; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D010100:Oxygen