ISOTOPICALLY SENSITIVE BRANCHING AND ITS EFFECT ON THE OBSERVED INTRAMOLECULAR ISOTOPE EFFECTS IN CYTOCHROME-P-450 CATALYZED-REACTIONS -A NEW METHOD FOR THE ESTIMATION OF INTRINSIC ISOTOPE EFFECTS
ISOTOPICALLY SENSITIVE BRANCHING AND ITS EFFECT ON THE OBSERVED INTRAMOLECULAR ISOTOPE EFFECTS IN CYTOCHROME-P-450 CATALYZED-REACTIONS -A NEW METHOD FOR THE ESTIMATION OF INTRINSIC ISOTOPE EFFECTS
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DOI：
10.1021/ja00282a037
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发表时间：
1986-10-29
影响因子：
15
通讯作者：
TRAGER, WF
中科院分区：
文献类型：
--
作者：
JONES, JP;KORZEKWA, KR;TRAGER, WF
合成了两种选择性氘代正辛烷（辛烷-1-2H3和辛烷-1，2，3-2H7），并利用苯巴比妥诱导的大鼠肝微粒体和纯化的细胞色素P-450 b进行了羟基化反应。这些实验的结果提供了证据，阐明了分支反应途径和酶-底物复合物的平衡之间的相互作用，以确定所观察到的同位素效应的大小。推导出一个方程，允许限制被放置在固有的同位素效应。该方程是基于所观察到的同位素效应和分支反应途径的区域选择性，由一种酶催化，通过一个单一的酶-底物复合物形成两种产物。由该方程确定的形成1-辛醇的固有同位素效应在9.5和9.8之间。
Two selectively deuterated n-octanes (octane-1-2H3 and octane-1,2,3-2H7) were synthesized and subjected to hydroxylation by phenobarbital-induced rat liver microsomes and purified cytochrome P-450b. The results of these experiments provide evidence which clarifies the interplay between a branched reaction pathway and the equilibration of an enzyme-substrate complex, in determining the magnitude of an observed isotope effect. An equation is derived that allows limits to be placed on the intrinsic isotope effect. The equation is based on the observed isotope effect and the regioselectivity of a branched reaction pathway, catalyzed by an enzyme that forms two products via a single enzyme-substrate complex. The intrinsic isotope effect for the formation of 1-octanol was determined by this equation to lie between 9.5 and 9.8.