The amino acid sequences of 3 forms of cytochromes-P450, cytochrome b5, and their respective reductases are under current investigation. Structure strategy for all five enzymes includes tryptic digestion of urea-denatured preparations, and cleavage with the glutamate protease from staphylococcus. Peptides are effectively resolved from such digests by high performance liquid chromatography (HPLC). Isolated peptides are sequenced on a semi-microscale (approximately 10-20 nm) using automated instrumentation. HPLC maps of tryptic digests of phenobarbital (Form 2), tetrachlorodibenzo-p-dioxin (Forms 4 and 6) induced cytochromes P-450 have been compared with those for the "normal" (uninduced) enzyme. The results indicate that these forms are unique gene products. We therefore intend to test the hypothesis that these enzymes' specificities may relate to constant and variable regions of amino acid sequence. The amino acid sequences of these microsomal electron transport proteins will provide a firm chemical foundation for structure/function studies, as well as provide information on membrane proteins and lipid interactions in general.