ABILITY OF CUMENE HYDROPEROXIDE AND NAIO4 TO SUPPORT MICROSOMAL HYDROXYLATIONS IN BIOSYNTHESIS AND METABOLISM OF BILE-ACIDS
ABILITY OF CUMENE HYDROPEROXIDE AND NAIO4 TO SUPPORT MICROSOMAL HYDROXYLATIONS IN BIOSYNTHESIS AND METABOLISM OF BILE-ACIDS
复制标题
DOI：
10.1016/0014-5793(76)80526-1
复制
发表时间：
1976-01-01
期刊：
影响因子：
3.5
通讯作者：
WIKVALL, K
中科院分区：
文献类型：
--
作者：
DANIELSSON, H;WIKVALL, K
最近的许多研究表明，枯烯氢过氧化物、其他有机过氧化物、NaI 〇 4和NaCl 〇 2可以在肝微粒体中的细胞色素P-450依赖性羟基化中取代NADPH和氧[1-7]。这些研究中使用的底物是各种药物、类固醇激素和劳里酸。使用NADPH和氧，劳里酸在11-位和12-位均被肝微粒体羟基化，而使用氢过氧化枯烯仅在11-位获得羟基化[5]。Ellin和Orrenius [5]得出结论，这一发现进一步支持了不同细胞色素P-450参与月桂酸11-和12-羟基化的论点。在一项广泛的研究中，在NADPH、氢过氧化枯烯或NaIO 4存在下，肝微粒体对不同位置的类固醇激素进行羟基化，Hrycay et al. [6，7]发现，由给定类固醇形成的产物的比率随羟基化剂而不同。结果表明，不同形式的细胞色素P-450与不同的亲合力的羟基化剂参与不同的羟基化。胆汁酸的生物合成和代谢包括许多微粒体羟基化[8]。日这些羟基化似乎都是细胞色素P-450依赖性的，但在一个或几个方面彼此不同。这些反应已经在由部分纯化的细胞色素P-450和NADPH-细胞色素P-450还原酶组成的重构系统中显示，目前正在尝试研究不同的羟化酶活性是否对应于不同的细胞色素P-450 [9]。与这个问题有关的信息可以从研究氢过氧化枯烯或NalO_4在这些羟基化中替代NADPH的能力中获得。本通讯报道了NADPH氢过氧化枯烯和NalO_4在胆汁酸生物合成和代谢中支持6/3-、7ix-、12 ix-、25-和26-羟基化的能力的比较。结果表明，这五个NADPH支持的羟基化，过氧化氢异丙苯只支持25-羟基化和NaI O 4只支持25-羟基化和在一个小的，但显着程度的6/3-羟基化。
A number of recent investigations have shown that cumene hydroperoxide, other organic peroxides, NalO4, and NaC102 can substitute for NADPH and oxygen in cytochrome P-450 dependent hydroxylations in liver microsomes [1-7]. The substrates used in these investigations have been various drugs, steroid hormones and laurie acid. With NADPH and oxygen, laurie acid is hydroxylated in both the 11-position and the 12-position by liver microsomes, whereas with cumene hydroperoxide hydroxylation was obtained only in the 11-position [5]. Ellin and Orrenius [5] concluded that this finding provided further support for the contention that different cytochromes P-450 are involved in 11-and 12-hydroxylation of lauric acid. In an extensive study of hydroxylations of steroid hormones in different positions by liver microsomes in the presence of NADPH, cumene hydroperoxide or NalO4, Hrycay et al.[6, 7] found that ratios of products formed from a given steroid differed with the hydroxylating agent. It was suggested that different forms of cytochrome P-450 with varying affinily for the hydroxylating agents were involved in the different hydroxylations. The biosynthesis and metabolism of bile acids include a number of microsomal hydroxylations [8]. Th. ese hydroxylations appear all to be cytochrome P-450 dependent but differ in one or several respects from each other. The reactions have been shown in reconstituted systems consisting of partially purified cytochrome P-450 and NADPH-cytochrome P-450 reductase, and attempts are being presently made to study whether or not the different hydroxylase activities correspond to different cytochromes P-450 [9]. Information relevant to this question might be obtained from a study of the ability of cumene hydroperoxide or NalO4 to substitute for NADPH in these hydroxylations.The present communication reports a comparison between NADPHI cumene hydroperoxide and NalO4 in their ability to support 6/3-, 7ix-, 12ix-, 25-and 26-hydroxylation in bile acid biosynthesis and metabolism. The results show that of these five NADPH-supported hydroxylations, cumene hydroperoxide supports only 25-hydroxylation and NalO4 only 25-hydroxylation and to a small but significant extent 6/3-hydroxylation.