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Thiol-Mediated NTA-Fe(III) Reduction and Lipid Peroxidation

1994; Elsevier BV; Volume: 312; Issue: 1 Linguagem: Inglês

10.1006/abbi.1994.1299

1096-0384

Nathan Spear, Steven D. Aust,

Arsenic contamination and mitigation

The nephrotoxicity of nitrilotriacetate chelated Fe(III) (NTA-Fe(III)) has been linked to the metabolism of glutathione (GSH) by γ-glutamyl transpeptidase and a dipeptidase. The products of these enzymes are cysteinyl-glycine (cys-gly) and cysteine (cys), which are proposed to be the reductants of NTA-Fe(III) to cause oxidative damage to various biomolecules. The ability of cys-gly and cys to cause in vitro NTA-Fe(III)-dependent lipid peroxidation correlated directly with their ability to reduce NTA-Fe(III). GSH reduced iron at a much slower rate and did not stimulate lipid peroxidation. It has been proposed that GSH, cys-gly and cys reduce iron at different rates because their thiols have different pKas. However, increasing the amount of GS−, by raising the pH, did not cause a corresponding increase in the rate of iron reduction. The monomethyl ester of GSH reduced NTA-Fe(III) at the same rate as GSH, but the dimethyl ester of GSH reduced NTA-Fe(III) approximately 30 times faster. From this we conclude that GSH does not reduce NTA-Fe(III) at the same rate as cys-gly and cys because of the liganding between GSH and the iron.