<P> CYP3A4 is a member of the cytochrome P450 family of oxidizing enzymes . Several other members of this family are also involved in drug metabolism, but CYP3A4 is the most common and the most versatile one . Like all members of this family, it is a hemoprotein, i.e. a protein containing a heme group with an iron atom . In humans, the CYP3A4 protein is encoded by the CYP3A4 gene . This gene is part of a cluster of cytochrome P genes on chromosome 7q21. 1 . </P> <P> CYP3A4 is a member of the cytochrome P450 superfamily of enzymes . The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids components . </P> <P> The CYP3A4 protein localizes to the endoplasmic reticulum, and its expression is induced by glucocorticoids and some pharmacological agents . Cytochrome P450 enzymes metabolize approximately 60% of prescribed drugs, CYP3A4 is responsible for about half of this metabolism, substrates include acetaminophen, codeine, ciclosporin (cyclosporin), diazepam, and erythromycin . The enzyme also metabolizes some steroids and carcinogens . Most drugs undergo deactivation by CYP3A4, either directly or by facilitated excretion from the body . Also, many substances are bioactivated by CYP3A4 to form their active compounds, and many protoxins being toxicated into their toxic forms (for examples--see table below). </P> <P> CYP3A4 also possesses epoxygenase activity in that it metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), i.e. (±) - 8, 9 -, (±) - 11, 12 -, and (±) - 14, 15 - epoxyeicosatrienoic acids . The EETs have a wide range of activities including the promotion of certain types of cancers (see epoxyeicosatetraenoic acid #cancer). CYP3A4 promotes the growth of various types of human cancer cell lines in culture by producing (±) - 14, 15 - epoxyeicosatrienoic acids which stimulate these cells to grow, The cytochrome P450 is also reported to have fatty acid monooxgenase activity for metabolizing arachidonic acid to 20 - Hydroxyeicosatetraenoic acid (20 - HETE). 20 - HETE has a wide range of activities that also include growth stimulation in breast and other types of cancers (see 12 - hydroxyeicosatetraenoic acid #cancer). </P>

Drugs that are substrates of cytochrome p450 3a4 and cyp2d6