The role of chelators in the catalysis of glutathione-gamma-glutamyl transpeptidase-dependent lipid peroxidation by transition metals.
A gamma-glutamyl transpeptidase-glutathione (GGT-GSH) system induces transition metal-dependent lipid peroxidation (LPO). The role of the transition metals iron and copper in this system was studied by determination of LPO rates, the rates of Fe3+ reduction, and the steady state concentration of Fe2+ as function of concentration of o-phenanthroline or citrate. Optimum curves were obtained, compatible with the idea that Fe2+ chelated by an entity other than o-phenanthroline or citrate is important in thiol-driven LPO. Cu enhanced LPO at low concentrations, inhibited LPO at high ones, and catalytically elevated the steady state concentration of Fe2+. Relating the steady states of Fe2+ at various chelator concentrations with those of LPO rates, indicate that a Fe(2+)-O-O-Fe3+ complex may not be the principal oxidizing entity. The above, and the resistance of LPO to catalase, superoxide dismutase and mannitol are compatible with the notion that the Fe which participates in redox cycles is chelated to an entity that may be refractory to the action of these antioxidants.
Zalit
I
I
Department of Biochemistry, Tel-Aviv University, Ramat-Aviv, Israel.
Glass
G A
GA
Stark
A A
AA
D000818:Animals; D002384:Catalysis; D002614:Chelating Agents / Q000494:pharmacology*; D019343:Citric Acid / Q000494:pharmacology; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007854:Lead / Q000494:pharmacology; D008024:Ligands; D015227:Lipid Peroxidation; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D002614:Chelating Agents; D005296:Ferrous Compounds; D008024:Ligands; D010618:Phenanthrolines; D013438:Sulfhydryl Compounds; D019343:Citric Acid; D007854:Lead; D003300:Copper; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C025205:1,10-phenanthroline