Abstract
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.
Keywords: Cytochrome P450, lipid-domain, membrane, nonbilayer, phospholipid
Current Protein & Peptide Science
Title: Functional Regulation of Hepatic Cytochrome P450 Enzymes by Physicochemical Properties of Phospholipids in Biological Membranes
Volume: 8 Issue: 5
Author(s): Taeho Ahn, Mihee Kim, Chul-Ho Yun and Han-Jung Chae
Affiliation:
Keywords: Cytochrome P450, lipid-domain, membrane, nonbilayer, phospholipid
Abstract: 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.
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Cite this article as:
Ahn Taeho, Kim Mihee, Yun Chul-Ho and Chae Han-Jung, Functional Regulation of Hepatic Cytochrome P450 Enzymes by Physicochemical Properties of Phospholipids in Biological Membranes, Current Protein & Peptide Science 2007; 8 (5) . https://dx.doi.org/10.2174/138920307782411392
DOI https://dx.doi.org/10.2174/138920307782411392 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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