Cytochrome P450 in Human Drug Metabolism: How Much Is Predictable?
Cytochrome P450 (CYP) mono-oxygenases represent one of the major enzyme systems that determine the organism’s capability of dealing with drugs and chemicals. Studies over the past 20 years have provided evidence that cytochromes P450 occur in many different forms (isoforms or isozymes) which differ in spectral, chemical, and immunological properties and have different substrate affinities. These isozymes also differ in their regulation and tissue distribution. Recombinant DNA studies indicate that between 50 and 200 structural genes may code for different cytochrome P450 isozymes in a single organism. Close to 30 human cytochrome P450 genes have now been characterized. The multiplicity of P450 isozymes explains in part the literally thousands of substrates known to be metabolized by this system (for review, see Nelson et al. 1993).
KeywordsMidazolam Clozapine Metoprolol Phenobarbital Dioxin
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