The cytochromes P-450 metabolize a wide array of compounds, including xenobiotics such as drugs and carcinogens, and endogenous compounds such as steroids and prostaglandins. The focus of this project is the characterization of structurefunction relationships and regulation of the multiple forms of this enzyme. Monoclonal antibodies (MAb's) to rat P-450's are a tool in these studies. Using a MAb to a nitrosamine-metabolizing ethanol-inducible rat liver P-450, a P-450 has been immunopurified from both rat and human liver. These differed in primary structure as evidenced by different amino terminal sequences and peptide maps. The membrane organization of P-450's was probed by a crosslinking study which revealed specific association among certain forms of P-450. Such interactions may influence the disposition of P-450 substrates in secondary metabolism. The induction of rat liver microsomal and nuclear envelope P-450's by 2-acetylaminofluorene (AAF) was immunochemically probed with MAb's to P-450c and P-450d. These P- 450's were induced in both microsomes and envelopes, although AAF decreased total P-450 in envelopes but not microsomes.
