MECHANISTIC STUDIES ON AROMATASE AND RELATED C-C BOND CLEAVING P-450 ENZYMES
MECHANISTIC STUDIES ON AROMATASE AND RELATED C-C BOND CLEAVING P-450 ENZYMES
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DOI：
10.1016/0960-0760(93)90241-n
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发表时间：
1993-03-01
影响因子：
4.1
通讯作者：
WRIGHT, JN
中科院分区：
文献类型：
--
作者：
AKHTAR, M;NJAR, VCO;WRIGHT, JN
一些P-450系统，特别是芳香酶和14 α-脱甲基酶不仅催化羟基化反应，而且催化醇氧化成羰基化合物以及C-C键断裂过程。所有这些反应都发生在相同的活性位点。17 α-羟化酶-17，20-裂解酶也有类似的情况，它参与羟化和C-C键裂解过程。由上述酶催化的C-C键裂解反应符合一般方程：[图表]有人认为，由这些酶催化的所有三种类型的反应可以被视为一个共同主题的变化。在P-450依赖性羟基化反应中，最初形成的Fe（III）-O-O'物质转化为Fe（III）-O-OH，后者的氧-氧键的异裂然后得到氧代衍生物，其可能具有许多典型结构;例如Fe（V）= O（+）。Fe（IV）= O Fe（IV）-O.其中之一是Fe（IV）-O。表现为烷氧基自由基，参与从C-H键上夺氢，产生Fe（IV）-OH和碳自由基。后者然后通过Fe（IV）-OH的羟基自由基的递送而猝灭。因此，后一种物质可被视为羟基自由基的载体。我们已经提出，C-C键裂解反应通过Fe（III）-O-OH物种的参与而发生，所述Fe（III）-O-OH物种被羰基化合物的亲电性质捕获，得到过氧化物加合物，所述过氧化物加合物碎片产生酰基-碳裂解。科学发展导致这一结论被认为是。在第一作者看来，“机制研究不是一种科学活动，而是一种文化活动。机制的目的不是绝对的真理，而是对一个领域的知识状况的“动态”评论。随着一个领域的结构性知识的进步，机制也在发展，以注意到新的发现。正如一个建设性的''运行''评论提供了更高的性能标准的刺激，所以机制要求更好和更坚定的结构信息，从他们的解释。
Some P-450 systems, notably aromatase and 14alpha-demethylase catalyse not only the hydroxylate reaction but also the oxidation of an alcohol into a carbonyl compound as well as a C-C bond cleavage process. All these reactions occur at the same active site. A somewhat analogous situation is noted with 17alpha-hydroxylase-17,20-lyase that participates in hydroxylation as well as C-C bond cleavage process. The C-C bond cleavage reactions catalysed by the above enzymes conform to the general equation:[GRAPHICS]It is argued that all three types of reaction catalyzed by these enzymes may be viewed as variations on a common theme. In P-450 dependent hydroxylation the initially formed Fe(III)-O-O' species is converted into Fe(III)-O-OH and the heterolysis of the oxygen-oxygen bond of the latter then gives the oxo-derivative for which a number of canonical structures are possible; for example Fe(V) = O (+.)Fe(IV) = O Fe(IV)-O.. One of these, Fe(IV)-O. behaves like an alkoxyl radical and participates in hydrogen abstraction from C-H bond to produce Fe(IV)-OH and carbon radical. The latter is then quenched by the delivery of hydroxyl radical from Fe(IV)-OH. The latter species may thus be regarded as a carrier of hydroxyl radical. We have proposed that the C-C bond cleavage reaction occurs through the participation of the Fe(III)-O-OH species that is trapped by the electrophilic property of the carbonyl compound giving a peroxide adduct that fragments to produce an acyl-carbon cleavage. Scientific developments leading up to this conclusion are considered. In the first author's views, ''The study of mechanisms is not a scientific but a cultural activity. Mechanisms do not aim at an absolute truth but are intended to be a ''running'' commentary on the status of knowledge in a field. As the structural knowledge in a field advances Mechanisms evolve to take note of the new findings. Just as a constructive ''running'' commentary provides the stimulus for higher standards of performance, so Mechanisms call for better and firmer structural information from their practitioners''.