P450 Enzyme Specificity

Jeurissen SM, Bogaards JJ, Awad HM, Boersma MG, Brand W, Fiamegos YC, van Beek TA, Alink GM, Sudholter EJ, Cnubben NH, Rietjens IM (2004) Human cytochrome P450 enzyme specificity for bioactivation of safrole to the proximate carcinogen I -hydroxysafrole. Chem Res Toxicol 17 1245-1250... 

Capdevila JH, Karara A, Waxman DJ, Martin MV, Falck JR, Guengerich FP. Cytochrome P450 enzyme-specific control of the regio- and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase. J Biol Chem 1990 265 10865-10871. 

The precursor, 7-dehydrocholesterol is converted by a non-enzymatic reaction to cholecalciferol (calciol). This reaction occurs in skin exposed to sunlight due to irradiation by UV-B light at a wavelength of about 300 nm. Cholecalciferol is transported via carrier proteins to the liver where hydroxylation at carbon-25 occurs in a reaction catalysed by a microsomal cytochrome P450 hydroxylase to form calcidiol. This compound travels to the kidney attached to specific binding proteins, where another cytochrome P450 enzyme, mitochondrial 1-a-hydroxylase, introduces a second hydroxyl group in to the molecule to form the active calcitriol. 

Metabolism - Repaglinide is completely metabolized by the liver. The cytochrome P450 enzyme system, specifically 3A4, is involved in the N-dealkylation of repaglinide. 

The flavin monooxygenases (FMOs) are a family of five enzymes (FMO 1-5) that operate in a manner analogous to the cytochrome P450 enzymes in that they oxidize the drug compound in an effort to increase its elimination. Though they possess broad substrate specificity, in general they do not play a major role in the metabolism of drugs but appear to be more involved in the metabolism of environmental chemicals and toxins. 

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