Lysophosphatidylserine-induced functional switch of human cytochrome P450 1A2 and 2E1 from monooxygenase to phospholipase D.
Interaction of human cytochrome P450 1A2 (CYP1A2) and 2E1 (CYP2E1) with phospholipid, lysophosphatidylserine (LysoPS) in the context of a PC matrix specifically stimulated the PLD activity of both enzymes in a LysoPS concentration-dependent manner. However, other anionic lysophospholipids as well as the neutral lysophospholipids, lysophosphatidylcholine and lysophosphatidylethanolamine, had no effect. LysoPS also accompanied conformational changes in both CYPs when assayed by circular dichroism. Although the PLD activity was decreased in the presence of components required for the monooxygenase (MMO) activity, including 100% PC membranes, NADPH-cytochrome P450 reductase and NADPH, as compared to the activity in the absence of the reducing system, LysoPS recovered the PLD activity in a concentration-dependent manner. Considering that LysoPS induced a decrease in the MMO activities of both CYPs, the results suggest that the functional roles of CYP1A2 and 2E1 can be switched by interaction with a specific anionic lysophospholipid in vivo.
Cho
Eun Yi
EY
School of Biological Sciences and Technology and Hormone Research Center, Chonnam National University Gwangju 500-757, Republic of Korea.
Yun
Chul-Ho
CH
Chae
Ho-Zoon
HZ
Chae
Han-Jung
HJ
Ahn
Taeho
T
D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000737:chemistry / Q000378:metabolism*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D019392:Cytochrome P-450 CYP2E1 / Q000737:chemistry / Q000378:metabolism*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010739:Phospholipase D / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D008246:Lysophospholipids; C025059:lysophosphatidylserine; D019392:Cytochrome P-450 CYP2E1; D019388:Cytochrome P-450 CYP1A2; D010739:Phospholipase D