Monooxygenases Cytochrome P450 enzymes

Since endosulfan is a cytochrome P450-dependent monooxygenase inducer, the quantification of specific enzyme activities (e.g., aminopyrine-A -demethylase, aniline hydroxylase) may indicate that exposure to endosulfan has occurred (Agarwal et al. 1978). Because numerous chemicals and drugs found at hazardous waste sites and elsewhere also induce hepatic enzymes, these measurements are nonspecific and are not necessarily an indicator solely of endosulfan exposure. However, these enzyme levels can be useful indicators of exposure, together with the detection of endosulfan isomers or the sulfate metabolite in the tissues or excreta. 

Fouchecourt, M.O. and J.L. Riviere. 1995. Activities of cytochrome P450-dependent monooxygenases and antioxidant enzymes in different organs of Norway rats (Rattus norvegicus) inhabiting reference and contaminated sites. Chemosphere 3L4375A386. 

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. 

Cytochromes P450 are monooxygenases whose cosubstrates, often NADH or NADPH, deliver electrons to the active center heme via a separate flavoprotein and often via an iron-sulfur protein as well 476a b A typical reaction (Eq. 18-55) is the 11 (3-hydroxylation of a steroid, an essential step in the biosynthesis of steroid hormones (Fig. 22-11). The hydroxyl group is introduced without inversion of configuration. The same enzyme converts unsaturated derivatives to epoxides (Eq. 18-56), while other cytochromes P450... 

Cytochrome P450 enzymes are important in pharmaceutical research and development, because of their roles in drug metabolism.129 They are a ubiquitous class of haem enzymes, which act as monooxygenases in a wide variety of biological reactions. 

In order to complete the indolopyrrolocarbazole ring system, CPA intermediates undergo a decarboxylative ring closure. This biosynthetic step is performed by a cytochrome P450 enzyme (rebP, staP) and a fiavin-dependent monooxygenase (rebC, staC). 

---