Phospholipase D activity of cytochrome P450 in human liver endoplasmic reticulum

Phospholipase D (PLD) activity in mammalian liver endoplasmic reticulum (ER ) has not been characterized, Purified human liver microsomal cytochromes P 450 (P450)-P450 1A2 and P450 2E1-were shown to have appreciable PLD activit y, hydrolyzing phosphatidylcholine but not other phospholipids, generating PA and choline, The activity was confirmed using recombinant and mutated hu man P450s expressed in bacteria. In human liver microsomes, immunoinhibitio n of PLD activity was observed with anti-P450 1A2 > anti-P450 2C > anti-P45 0 2E1, Thus, P450 may act as a significant PLD in human liver ER and exert its biological effects by several mechanisms, including signaling functions and change of membrane properties. (C) 1999 Academic Press.