title: Endogenous epoxyeicosatrienoyl-phospholipids. A novel class of cellular glycerolipids containing epoxidized arachidonate moieties.
abstract: By chromatographic and mass spectral techniques we document in rat liver the presence of new classes of glycerophospholipids which contain an epoxyeicosatrienoate moiety, esterified to the glycerol-sn-2 position. These novel lipids are formed in vivo from endogenous precursors and under physiological conditions. Chromatographic resolution followed by hydrolysis and regioisomeric analysis showed that they consist of the 8,9-, 11,12-, and 14,15-epoxyeicosatrienoyl derivatives of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Their relative concentrations (micromoles of oxidized lipid/mol of phospholipid) were 70, 85, and 106 for phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, respectively. Chiral analysis of the fatty acids at sn-2 revealed an enantioselective preference for 8(S),9(R)-, 11(S),12(R)-, and 14(R),15(S)-epoxyeicosatrienoates in all three lipid classes. The data suggest a multienzyme process initiated by cytochrome P-450 epoxidation of arachidonic acid followed by ATP-dependent activation to epoxyeicosatrienoyl-CoA derivatives and stereoselective lysolipid acylation. These results provide a molecular basis for a potential physiological role of cytochrome P-450 in the biosynthesis of unique cellular glycerolipids and, consequently, in the control of cell membrane structure and function.
authors.affiliation: Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232.
authors.forename: A
authors.initials: A
authors.lastname: Karara
authors.forename: E
authors.initials: E
authors.lastname: Dishman
authors.forename: J R
authors.initials: JR
authors.lastname: Falck
authors.forename: J H
authors.initials: JH
authors.lastname: Capdevila
mesh_terms: D000215:Acylation; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000737:chemistry*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003065:Coenzyme A / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000737:chemistry; D010712:Phosphatidic Acids / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010716:Phosphatidylinositols / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D001095:Arachidonic Acids; D004852:Epoxy Compounds; D008244:Lysophosphatidylcholines; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010743:Phospholipids; D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; D003065:Coenzyme A