Cooperative properties of cytochromes P450.

Cooperative properties of cytochromes P450.
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细胞色素P450的合作特性。

DOI:
10.1016/j.pharmthera.2009.05.011
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发表时间:
2009-11
影响因子:
13.5
通讯作者:
Sligar SG
Sligar SG
中科院分区:
医学1区
文献类型:
--
作者:
Denisov IG;Frank DJ;Sligar SG

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细胞色素P450是一类重要的血红素单加氧酶,具有广泛的底物和相应的功能,从类固醇激素的生物合成到异种生物的代谢。尽管经过数十年的研究,在新陈代谢过程中,这个超级家族的许多成员所观察到的复杂的非米切里斯行为的分子机制,通常被称为“协同性”,仍有待充分阐明。尽管有证据表明寡聚化可能在定义所观察到的协同性中起重要作用,但一些单体细胞色素P450,特别是那些参与异种代谢的细胞色素P450,也表现出这种行为,因为它们能够同时结合几个底物分子。因此,形成具有不同化学计量和功能特性的不同酶-底物配合物可以产生同向性和异向性的合作行为。本文综述了目前对细胞色素P450协同作用的认识,重点介绍了单体酶协同作用的性质。
Cytochromes P450 form a large and important class of heme monooxygenases with a broad spectrum of substrates and corresponding functions, from steroid hormone biosynthesis to the metabolism of xenobiotics. Despite decades of study, the molecular mechanisms responsible for the complex non-Michaelis behavior observed with many members of this super-family during metabolism, often termed ‘cooperativity,’ remain to be fully elucidated. Although there is evidence that oligomerization may play an important role in defining the observed cooperativity, some monomeric cytochromes P450, particularly those involved in xenobiotic metabolism, also display this behavior due to their ability to simultaneously bind several substrate molecules. As a result, formation of distinct enzyme-substrate complexes with different stoichiometry and functional properties can give rise to homotropic and heterotropic cooperative behavior. This review aims to summarize the current understanding of cooperativity in cytochromes P450, with a focus on the nature of cooperative effects in monomeric enzymes.
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发表时间: 2008-10-28
期刊: BIOCHEMISTRY
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