Lysophosphatidylserine-induced functional switch of human cytochrome P450 1A2 and 2E1 from monooxygenase to phospholipase D

Biochem Biophys Res Commun. 2008 Nov 21;376(3):584-9. doi: 10.1016/j.bbrc.2008.09.023. Epub 2008 Sep 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A2 / chemistry
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Cytochrome P-450 CYP1A2 Inhibitors
  • Cytochrome P-450 CYP2E1 / chemistry
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Cytochrome P-450 CYP2E1 Inhibitors
  • Humans
  • Lysophospholipids / chemistry
  • Lysophospholipids / metabolism*
  • Lysophospholipids / pharmacology
  • Phospholipase D / chemistry
  • Phospholipase D / metabolism*
  • Protein Conformation
  • Rats


  • Cytochrome P-450 CYP1A2 Inhibitors
  • Cytochrome P-450 CYP2E1 Inhibitors
  • Lysophospholipids
  • lysophosphatidylserine
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 CYP1A2
  • Phospholipase D