白三烯A4作为细胞色素P-450催化5-氢过氧化二十碳四烯酸转化为白三烯B4过程中的中间体的证据。

Evidence for leukotriene A4 as an intermediate in the conversion of 5-HPETE to leukotriene B4 catalyzed by cytochrome P-450.

作者信息

Bösterling B, Trudell J R

出版信息

Biochem Biophys Res Commun. 1983 Sep 30;115(3):995-1001. doi: 10.1016/s0006-291x(83)80033-3.

Abstract

Hydrolysis of 5-hydroperoxyeicosatetraenoic acid catalyzed by cytochrome P-450 in the absence of NADPH formed a product with spectral and HPLC characteristics identical with those of leukotriene B4, 5(S),12(R)-dihydroxy-6-cis,8,10-trans,14-cis-eicosatetraenoic acid (LTB4). The product mixture suggests that trans-5,6-oxido-7,9-trans,11,14-cis-eicosatetraenoic acid, leukotriene A4 (LTA4) is an intermediate in the reaction. We suggest that the formation of LTB4 with the essential 6-cis stereochemistry is due to tight binding of the 5-HPETE to the cytochrome P-450 at a site that does not allow it to isomerize to the kinetically favored 6,8,10-trans configuration during attack of hydroxyl ion at C-12.

摘要

在没有烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的情况下，细胞色素P-450催化5-氢过氧化二十碳四烯酸水解，形成了一种产物，其光谱和高效液相色谱特征与白三烯B4、5(S),12(R)-二羟基-6-顺式,8,10-反式,14-顺式二十碳四烯酸（LTB4）相同。产物混合物表明反式-5,6-环氧-7,9-反式,11,14-顺式二十碳四烯酸，即白三烯A4（LTA4）是该反应的中间体。我们认为，具有必需的6-顺式立体化学结构的LTB4的形成是由于5-氢过氧化二十碳四烯酸（5-HPETE）在细胞色素P-450上的一个位点紧密结合，该位点不允许其在氢氧根离子进攻C-12时异构化为动力学上更有利的6,8,10-反式构型。