Hydrocarbon Hydroxylation by Cytochrome P450 Enzymes

Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, California 94158-2517, USA.
Chemical Reviews (Impact Factor: 46.57). 09/2009; 110(2):932-48. DOI: 10.1021/cr9002193
Source: PubMed


A study was conducted to demonstrate hydrocarbon hydroxylation by cytochrome P450 enzymes. The cytochrome P450 enzymes were defined by the presence in the proteins heme prosthetic group coordinated on the proximal side by a thiolate ion. Investigations revealed that the principles of cytochrome P450 enzymes hydrocarbon hydroxylation applied to other hydroxylation reactions, including those that occurred on carbons adjacent to nitrogen, sulfur, or oxygen. The P450 enzyme was in the ferric state and had a thiolate proximal ligand and the distal ligand was a water molecule. Reduction in the ferrous enzyme was followed by binding of molecular oxygen to give the ferrous dioxy complex. This complex was observed and characterized by P450 cam by diverse physical techniques.

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    • "CYP enzymes comprise a superfamily of microsomal enzymes present predominantly in the liver. Multiple CYP enzymes catalyze the oxidation of chemicals of endogenous and exogenous origin, including drugs, steroids, prostanoids, eicosanoids, fatty acids, and environmental toxins [1]. CYP2D6 and CYP3A4 are the two most important isoforms in the CYP superfamily which play a pivotal role in drug metabolism. "
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    • "The biotransformation of drugs in metabolites has essentially enzymatic character, and the catalytic hemoproteins of CYP450 family, present in all forms of life (plants, bacteria, mammals), are known for their role in the metabolism of non-polar compounds [17] [18]. The reactions of hydroxylation of saturated carbonehydrogen bonds, epoxidation of double bonds, oxidation of heteroatoms, dealkylation and oxidations of aromatic carbons are catalyzed by CYP450 enzymes [17]. "
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