Isoenzyme-specific phosphorylation of cytochromes P-450 and other drug metabolizing enzymes.

Abstract A series of fourteen cytochrome P-450 isoenzymes was treated with three different protein kinases and found to devide into isoenzymes phosphorylated (i) by both the cyclic AMP-dependent kinase and the calcium-phospholipid-dependent kinase (P-450 PB 3a and PB 2e), (ii) by none of these kinases (P-450 PB 1b, MC 1b, UT 1, and thromboxane synthase), and (iii) by either the cyclic AMP-dependent kinase (P-450 LM 2, PB 2d, and PB 3b) or the calcium-phospholipid-dependent kinase (P-450 PB 1a, PB 2a, MC 1a, LM 3c, and LM 4). Other components of the monooxygenase system, cytochrome P-450 reductase, cytochrome b5, cytochrome b5 reductase as well as microsomal epoxide hydrolase, were poor subs…