The cytochrome P450 4 (CYP4) family

1. The CYP4 family consists of 11 subfamilies (CYP4A-CYP4M), which encode constitutive and inducible isozymes expressed in both mammals and insects. 2. The CYP4A subfamily encodes several cytochrome P450 enzymes that are capable of hydroxylating the terminal omega-carbon and, to a lesser extent, the (omega-1) position of saturated and unsaturated fatty acids, as well as enzymes active in the omega-hydroxylation of various prostaglandins. 3. The CYP4A1, A2 and A3 genes, the most extensively studied members of the CYP4 family, are expressed constitutively in rat liver and kidney and their expression is induced by a class of chemicals known as peroxisome proliferators, which includes the hypolipidemic drug, clofibrate. 4. Induction of CYP4A expression by clofibrate is due to transcriptional activation, mediated possibly via a peroxisome proliferator activated receptor (PPAR). 5. CYP4A gene expression is hormonally regulated. 6. The CYP4A1-3 genes are expressed constitutively and following induction in pregnant and lactating rats. 7. Translactational and transplacental induction of the CYP4A1-3mRNAs and proteins has been demonstrated. 8. There is a close association between microsomal CYP4A1 induction, peroxisome proliferation and induction of the peroxisomal fatty acid metabolizing system. 9. The CYP4A subfamily may be involved in the metabolism of arachidonic acid leading to the formation of physiologically important metabolites involved in such processes as blood flow in the kidney, cornea and brain.