Functional regulation of hepatic cytochrome p450 enzymes by physicochemical properties of phospholipids in biological membranes.
Knowledge regarding the regulation of hepatic cytochrome P450 (P450) is crucial to the fields of drug therapy and drug development, as well as to our understanding of the mechanisms underlying the metabolic activation of toxic and carcinogenic compounds. P450 is a membrane-anchored protein that shows a variety of interaction with membrane phospholipids, which affect the membrane topology and catalytic activities of the protein. In particular, anionic phospholipids, nonbilayer forming lipids, and the degree of saturation of the lipid fatty acyl chain play important roles in the functional regulation of P450, as well as in the bilayer structure of the membrane. However, despite the importance of phospholipids in the regulation of P450s, the interaction of the protein with membrane phospholipids, and the membrane properties induced by phospholipids which regulate P450, are unclear. In this review, we describe the effect of the physicochemical properties of the phospholipid constituents of biological membranes on hepatic P450 catalytic activity, membrane insertion (and/or penetration), and structural changes.
Ahn
Taeho
T
Department of Biochemistry, College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea. thahn@chonnam.ac.kr
Kim
Mihee
M
Yun
Chul-Ho
CH
Chae
Han-Jung
HJ
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008954:Models, Biological; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding
D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D003577:Cytochrome P-450 Enzyme System