Steroid metabolism by constitutive cytochromes P450.

In rat liver endoplasmic reticulum some 16 different cytochromes P450 have been identified as constitutive, sequenced from recombinant DNA, and shown to be distinct gene products. These forms are "multipurpose", i.e. functional in xenobiotic metabolism as well as endogenous substrate metabolism. In the latter case, these forms metabolize steroids, fatty acids, prostaglandins and even ketone bodies, indicating an involvement in homeostasis. In steroid metabolism, in contrast to "biosynthetic" forms of P450 which generally yield one product, the multipurpose forms exhibit broad, overlapping metabolite profiles, with isomeric and epimeric specificity and different mechanisms of product formation. The nature of the substrate docking region is of much interest and attempts have been made to rationalize the manner in which multiple metabolites are produced from a single substrate. Brain, with a very low level of P450 relative to liver also catalyzes steroid metabolism. The nature of the forms involved are not yet known.