期刊
CURRENT DRUG METABOLISM
卷 2, 期 2, 页码 93-115出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389200013338694
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资金
- NCI NIH HHS [R35 CA44353] Funding Source: Medline
- NIEHS NIH HHS [P30 ES00267] Funding Source: Medline
Cytochrome P450 (P450) enzymes play major roles in the metabolism of drugs, carcinogens, steroids, eicosanoids, alkaloids, pesticides, and other important xenobiotics, as well as chemicals normally endogenous to the body. P450s are generally considered in a classical catalytic reduction-oxidation cycle and an odd-electron abstraction/rebound chemical mechanism that can be used to rationalize carbon hydroxylation, dealkylation of heteroatomic substrates, heteroatom oxygenation, and the I oxidation of unsaturated compounds to epoxides and phenols. However, many other reactions are catalysed by P450s but not generally appreciated. The classical catalytic mechanism requires some expansion to explain all of these reactions. Reactions discussed here include mechanism-based heme inactivation, mechanism-based protein modification, 1,2-shifts, 1- and 2-electron reductions, I-electron oxidation, oxidative cleavage of carboxylic acid esters, desaturation, deformylation of aldehydes, ring formation, ipso mechanisms for aryl dehalogenation and O- and N-dearylation, cis-trans bond isomerization, several rearrangements of oxidized eicosanoids, aldoxime dehydration, and hydrolysis of phosphatidylcholine.
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