Cytochrome P450 Steroid Oxidations: Answers and More Questions
Cytochrome P450 (P450) enzymes are involved in the metabolism of drugs, carcinogens, and steroids. In the case of the steroid oxidations, P450 deficiencies can result in endocrine maladies. Our laboratory has been interested in several human P450s involved in sterol metabolism, including issues related to diseases, and a number of chemical, biochemical, and biophysical approaches have been applied to studying human P450s 7A1, 17A1, 19A1, and 21A2. P450 17A1 is of particular interest because of its two-step conversion of 21- to 19-carbon steroids, in light of other work on processive vs. distributive multi-step P450 reactions. Structural studies with two fish P450s, 17A1 and 17A2, may be instructive regarding the multi-step reaction. The catalytic mechanism of P450 19A1, the steroid aromatase, is also under investigation.