Lipophilic xenobiotics monooxygenases

Monooxygenases (MOs) Enzyme systems of the endoplasmic reticulum of many cell types, which can catalyze the oxidation of a great diversity of lipophilic xenobiotics, are particularly well developed in hepatocytes. Forms of cytochrome P450 constitute the catalytic centers of monooxygenases. 

Microsomes isolated from hepatic tissue appear to retain all of the mixed-function oxidase capabilities of intact hepa-tocytes because of this, microsomal preparations (with the necessary cofactors, e.g.. NADPH. Mg- ) are u.scd frequently for in vitro drug metabolism studies. Because of its membrane-bound nature, the cytochrome P-450 monooxy-gena.se system appears to be housed in a lipoidal environment. This may explain, in part, why lipophilic xenobiotics arc generally good sub.straics for the monooxygenase system. ... 

Xenobiotics are metabolized in two phases. The major reaction of phase 1 is hydroxylation catalyzed by a variety of monooxygenases, also known as the cytochrome P450s. In phase 2, the hydroxylated species are conjugated with a variety of hydrophihc compounds such as glucuronic acid, sulfate, or glutathione. The combined operation of these two phases renders lipophilic compounds into water-soluble compounds that can be ehminated from the body. 

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