Spear N, Aust S D
Biotechnology Center, Utah State University, Logan 84322-4705.
Arch Biochem Biophys. 1994 Jul;312(1):198-202. doi: 10.1006/abbi.1994.1299.
The nephrotoxicity of nitrilotriacetate chelated Fe(III) (NTA-Fe(III)) has been linked to the metabolism of glutathione (GSH) by gamma-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.
次氮基三乙酸螯合铁（III）（NTA-Fe(III)）的肾毒性与γ-谷氨酰转肽酶和二肽酶对谷胱甘肽（GSH）的代谢有关。这些酶的产物是半胱氨酰甘氨酸（cys-gly）和半胱氨酸（cys），它们被认为是将NTA-Fe(III)还原从而对各种生物分子造成氧化损伤的还原剂。cys-gly和cys引起体外NTA-Fe(III)依赖性脂质过氧化的能力与其还原NTA-Fe(III)的能力直接相关。GSH还原铁的速度要慢得多，并且不会刺激脂质过氧化。有人提出，GSH、cys-gly和cys以不同速度还原铁是因为它们的硫醇具有不同的pKa值。然而，通过提高pH值增加GS-的量，并不会导致铁还原速率相应增加。GSH单甲酯还原NTA-Fe(III)的速度与GSH相同，但GSH二甲酯还原NTA-Fe(III)的速度快约30倍。由此我们得出结论，由于GSH与铁之间的配位作用，GSH还原NTA-Fe(III)的速度与cys-gly和cys不同。
