MECHANISMS OF INACTIVATION OF LIPOXYGENASES BY PHENIDONE AND BW755C
MECHANISMS OF INACTIVATION OF LIPOXYGENASES BY PHENIDONE AND BW755C
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DOI：
10.1021/bi00101a008
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发表时间：
1991-09-17
期刊：
影响因子：
2.9
通讯作者：
MANSUY, D
中科院分区：
文献类型：
--
作者：
CUCUROU, C;BATTIONI, JP;MANSUY, D
吡唑啉衍生物菲尼酮和BW 755 C对大豆脂氧合酶（L-1）和马铃薯5-脂氧合酶（5-PLO）的抑制作用仅发生在这些化合物被脂氧合酶的过氧化物酶样活性氧化后。这种氧化与L-1的不可逆失活之间存在明确的关系。由L-1氧化菲尼酮的最终产物4，5-二脱氢菲尼酮不负责该失活，但衍生自菲尼酮的单电子氧化的物质在L-1失活中起关键作用。在不存在O2的情况下，1 mol L-1的失活发生在34 mol非尼酮氧化和0.8 mol非尼酮衍生代谢物与L-1共价结合后。在存在O2的情况下，1 mol L-1的失活在11 mol非尼酮氧化后已经发生，并且仅涉及0.4 mol非尼酮衍生代谢物与L-1的共价结合。提出了非尼酮灭活L-1的机制，包括非尼酮代谢物与蛋白质的不可逆结合和L-1氨基酸残基的氧化（在O2存在下）。
Inhibition of soybean lipoxygenase (L-1) and Potato 5-lipoxygenase (5-PLO) by the pyrazoline derivatives phenidone and BW755C only occurs after oxidation of these compounds by the peroxidase-like activity of the lipoxygenases. There is a clear relationship between this oxidation and the irreversible inactivation of L-1. The final product of phenidone oxidation by L-1, 4,5-didehydrophenidone, is not responsible of this inactivation, but the species derived from a one-electron oxidation of phenidone plays a key role in L-1 inactivation. In the absence of O2, inactivation of 1 mol of L-1 occurs after the oxidation of 34 mol of phenidone and the covalent binding of 0.8 mol of phenidone-derived metabolite(s) to L-1. In the presence of O2, inactivation of 1 mol of L-1 occurs already after oxidation of 11 mol of phenidone and only involves the covalent binding of 0.4 mol of phenidone-derived metabolite(s) to L-1. A mechanism is proposed for L-1 inactivation by phenidone, which involves the irreversible binding of a phenidone metabolite to the protein and the oxidation of an L-1 amino acid residue (in the presence of O2).