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Title
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Regioselective versatility of monooxygenase reactions catalyzed by CYP2B6 and CYP3A4 : examples with single substrates
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Author
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Abstract
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| Hepatic microsomal cytochrome P450 (CYP) enzymes have broad and overlapping substrate specificity and catalyze a variety of monooxygenase reactions, including aliphatic and aromatic hydroxylations, N-hydroxylations, oxygenations of heteroatoms (N, S, P and I), alkene and arene epoxidations, dehalogenations, dehydrogenations and N-, O- and S-dealkylations. Individual CYP enzymes typically catalyze the oxidative metabolism of a common substrate in a regioselective and stereoselective manner. In addition, different CYP enzymes often utilize different monooxygenase reactions when oxidizing a common substrate. This review examines various oxidative reactions catalyzed by a CYP enzyme acting on a single substrate. In the first example, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a halogenated aromatic environmental contaminant, was oxidatively biotransformed by human CYP2B6. Nine different metabolites of BDE-47 were produced by CYP2B6 via monooxygenase reactions that included aromatic hydroxylation, with and without an NIH-shift, dealkylation and debromination. In the second example, lithocholic acid (3a-hydroxy-5 beta-cholan-24-oic acid), an endogenous bile acid, served as a substrate for human CYP3A4 and yielded five different metabolites via aliphatic hydroxylation and dehydrogenation reactions. |
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Language
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English
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Source (journal)
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Advances in experimental medicine and biology. - New York, N.Y.
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CYTOCHROME P450
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Publication
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Berlin
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Springer-verlag berlin
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2015
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ISBN
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978-3-319-16008-5
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978-3-319-16009-2
978-3-319-16008-5
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DOI
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10.1007/978-3-319-16009-2_5
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Volume/pages
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851
(2015)
, p. 131-149
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ISI
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000361819000006
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Pubmed ID
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26002734
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Full text (Publisher's DOI)
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