With respect to arachidonic acid, linoleic acid, and other polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, CYP2C9 exhibits epoxygenase activity, i.e. it metabolizes these long-chain polyunsaturated fatty acids to their biologically active epoxides. For example, it is one of the principle cytochrome P450 enzymes that metabolizes arachidonic acid to the following eicosatrienoic acid epoxides: 5,6-epoxy-8Z,11Z,14Z-eicosatetrienoic acid, 5,6-epoxy-8Z,11Z,14Z-eicosatetrienoic acid, 11,12-epoxy-5Z,8Z,14Z-eicosatetrienoic acid, and 14,15-epoxy-5Z,8Z,11Z-eicosatetrainoic acid; animal models and a limited set of human studies implicate these epoxides in reducing hypertension; protecting against the Myocardial infarction and other insults to the heart; promoting the growth and metastasis of certain cancers; inhibiting inflammation; stimulating blood vessel formation; and possessing a variety of actions on neural tissues including modulating Neurohormone release and blocking pain perception (see epoxyeicosatrienoic acid and epoxygenase pages).
Multiple in vivo studies also show that several mutant CYP2C9 genotypes are associated with significant reduction of in metabolism and daily dose requirements of selected CYP2C9 substrate. In fact, adverse drug reactions (ADRs) often result from unanticipated changes in CYP2C9 enzyme activity secondary to genetic polymorphisms. Especially for CYP2C9 substrates such as warfarin and phenytoin, diminished metabolic capacity because of genetic polymorphisms or drug-drug interactions can lead to toxicity at normal therapeutic doses.
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