Cytochrome P450 and biological hydroxylation reactions.

Cytochrome P450 and biological hydroxylation reactions.
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细胞色素 P450 和生物羟基化反应。

DOI:
10.1007/bfb0019663
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发表时间:
1979
影响因子:
8.6
通讯作者:
V. Ullrich
V. Ullrich
中科院分区:
化学2区
文献类型:
--
作者:
V. Ullrich

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分子氧(现在称为双氧)作为有氧生命系统中的能量提供源的重要作用一直是显而易见的,但这种能量用于驱动生物氧化的机制多年来一直存在争议。在20世纪30年代中期,O.瓦尔堡1)从铁催化氧化与分子氧的模型研究中得出结论,分子氧分子的活化是生物氧化的关键事件,在此。时间仍然是相当不明确的定义,并认为主要是由糖酵解和线粒体呼吸。与此相反,H. Wieland 2)是脱氢假说的支持者,该假说认为氧分子仅仅是底物氢的电子汇。正是这种机制被证明对细胞中的所有能量产生反应都是正确的。瓦尔堡关于氧活化的想法几乎被人遗忘,直到1955年梅森和林石用稳定同位素1802证明,通过将分子氧直接掺入有机化合物而进行的生物氧化在自然界中相当普遍。这些发现引发了对相应酶促反应的研究热潮。现已确定,这些氧合作用是由多种双氧活化酶催化的,这些酶被Hayaishi等人命名为”加氧酶”。根据是将两个氧原子还是仅一个原子引入底物中,提出了”双加氧酶”和”单加氧酶”的亚分类,并建立了以下化学计量:
The essential role of molecular oxygen, now termed dioxygen, as an energy providing source in aerobic living systems has always been evident but the mechanism by which this energy is used to drive biological oxidations has been controversial for many years. In the mid 1930" s O. Warburg 1) concluded from model studies of ironcatalyzed oxidations with molecular oxygen that an activation of the dioxygen molecule was the crucial event for biological oxidations, which at that. time were still rather ill defined and thought mainly to consist of glycolysis and mitochondrial respiration. In contrast, H. Wieland 2) was the proponent of the dehydrogenation hypothesis which considered the oxygen molecule merely as an electron sink for substrate hydrogen. It was this mechanism which proved to be correct for all energy producing reactions in the cell. Warburg's idea of oxygen activation was almost forgotten until in 1955 Mason 3) and Hayaishi 4) demonstrated, using the stable isotope 1802, that biological oxidations which proceed by a direct incorporation of dioxygen into organic compounds are rather common in nature. These findings initiated a boom in the research on the corresponding enzymic reactions. It is now established that these oxygenations are catalyzed by a variety of dioxygen activating enzymes, which were designated" oxygenases" by Hayaishi s). Depending on whether both oxygen atoms or only one atom are introduced into the substrate, a subclassification into" dioxygenases" and" monooxygenases" was proposed and the following stoichiometry established: