O'Donnell V B, Smith G C, Jones O T
Division of Biochemical Sciences, Rowett Research Institute, Aberdeen, UK.
Mol Pharmacol. 1994 Oct;46(4):778-85.
Iodonium inhibition of the flavoenzymes neutrophil NADPH oxidase and cytochrome P450 reductase has been suggested to require reductive metabolism of the inhibitor to a phenyl radical. Inhibition would ultimately result from covalent attachment of phenyl radicals to either the flavin cofactor or adjacent amino acid side chains important in catalysis. In this paper we provide evidence, using EPR techniques, that phenyl radicals are formed during reaction of iodonium diphenyl with reduced free flavin (FMN) and protein-bound (cytochrome P450 reductase or xanthine oxidase) flavin. Kinetic analysis indicated iodonium diphenyl to be an uncompetitive inhibitor of xanthine oxidase, suggesting the need for reduced enzyme for inhibition. A study of the catalytic and structural properties of different flavoenzymes suggested that only enzymes containing flavins that function in one-electron transfer are targets for iodonium inhibition.
有人提出，碘鎓对黄素酶中性粒细胞NADPH氧化酶和细胞色素P450还原酶的抑制作用需要将抑制剂还原代谢为苯基自由基。抑制作用最终将源于苯基自由基与黄素辅因子或催化中重要的相邻氨基酸侧链的共价结合。在本文中，我们使用电子顺磁共振技术提供证据表明，在二苯基碘鎓与还原型游离黄素（FMN）以及与蛋白质结合的（细胞色素P450还原酶或黄嘌呤氧化酶）黄素反应过程中会形成苯基自由基。动力学分析表明二苯基碘鎓是黄嘌呤氧化酶的非竞争性抑制剂，这表明抑制作用需要还原型酶。对不同黄素酶的催化和结构特性的研究表明，只有含有在单电子转移中起作用的黄素的酶才是碘鎓抑制的目标。
