Abstract
Human platelets contain a soluble enzyme or enzyme system that catalyzes the formation of lysophosphatidylinositol and a compound more polar than arachidonic acid (compound A) from 2-arachidonoyl sn-phosphatidylinositol. Arachidonic acid, 2-arachidonoyl sn-phosphatidylcholine, or 2-arachidonoyl sn-phosphatidylethanolamine did not serve as substrate for the production of compound A. The reaction required Ca2+ and was not affected by aspirin, indomethacin, or mepacrin. Enzyme activity was not enhanced in the presence of NADPH, but it was inhibited greater than 90% by CO or N2; inhibition was readily reversible by exposure to atmospheric air. Neither metapyrone (SKF 525A) nor cyanide, inhibitors of cytochrome P-450, inhibited compound A formation, suggesting that a cytochrome P-450 system was not involved. Thrombin stimulated the formation of compound A in whole platelets; ionophore A23187 did so much less effectively; and other agonists such as collagen, ADP, and epinephrine were ineffective. Compound A exhibited a fragmentation pattern by GC/MS identical to that of authentic cis-14,15-oxido-5,8,11-icosatrienoic acid. Collectively, these data indicate that human platelets may contain an enzyme system that catalyzes the epoxidation of the arachidonic acid moiety of phosphatidylinositol and its hydrolysis to liberate cis-14,15-oxido-5,8,11-icosatrienoic acid.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ballou L. R., Cheung W. Y. Inhibition of human platelet phospholipase A2 activity by unsaturated fatty acids. Proc Natl Acad Sci U S A. 1985 Jan;82(2):371–375. doi: 10.1073/pnas.82.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ballou L. R., Cheung W. Y. Marked increase of human platelet phospholipase A2 activity in vitro and demonstration of an endogenous inhibitor. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5203–5207. doi: 10.1073/pnas.80.17.5203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ballou L. R., DeWitt L. M., Cheung W. Y. Substrate-specific forms of human platelet phospholipase A2. J Biol Chem. 1986 Mar 5;261(7):3107–3111. [PubMed] [Google Scholar]
- Bell R. L., Kennerly D. A., Stanford N., Majerus P. W. Diglyceride lipase: a pathway for arachidonate release from human platelets. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3238–3241. doi: 10.1073/pnas.76.7.3238. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Black H. S., Douglas D. R. A model system for the evaluation of the role of cholesterol -oxide in ultraviolet carcinogenesis. Cancer Res. 1972 Dec;32(12):2630–2632. [PubMed] [Google Scholar]
- Brash A. R. Specific lipoxygenase attack on arachidonate and linoleate esterified in phosphatidylcholine: precedent for an alternative mechanism in activation of icosanoid biosynthesis. Adv Prostaglandin Thromboxane Leukot Res. 1985;15:197–199. [PubMed] [Google Scholar]
- Capdevila J., Chacos N., Falck J. R., Manna S., Negro-Vilar A., Ojeda S. R. Novel hypothalamic arachidonate products stimulate somatostatin release from the median eminence. Endocrinology. 1983 Jul;113(1):421–423. doi: 10.1210/endo-113-1-421. [DOI] [PubMed] [Google Scholar]
- Capdevila J., Chacos N., Werringloer J., Prough R. A., Estabrook R. W. Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5362–5366. doi: 10.1073/pnas.78.9.5362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Capdevila J., Chacos N., Werringloer J., Prough R. A., Estabrook R. W. Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5362–5366. doi: 10.1073/pnas.78.9.5362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Capdevila J., Marnett L. J., Chacos N., Prough R. A., Estabrook R. W. Cytochrome P-450-dependent oxygenation of arachidonic acid to hydroxyicosatetraenoic acids. Proc Natl Acad Sci U S A. 1982 Feb;79(3):767–770. doi: 10.1073/pnas.79.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Capdevila J., Parkhill L., Chacos N., Okita R., Masters B. S., Estabrook R. W. The oxidative metabolism of arachidonic acid by purified cytochromes P-450. Biochem Biophys Res Commun. 1981 Aug 31;101(4):1357–1363. doi: 10.1016/0006-291x(81)91597-7. [DOI] [PubMed] [Google Scholar]
- Capdevila J., Pramanik B., Napoli J. L., Manna S., Falck J. R. Arachidonic acid epoxidation: epoxyeicosatrienoic acids are endogenous constituents of rat liver. Arch Biochem Biophys. 1984 Jun;231(2):511–517. doi: 10.1016/0003-9861(84)90415-6. [DOI] [PubMed] [Google Scholar]
- Chacos N., Falck J. R., Wixtrom C., Capdevila J. Novel epoxides formed during the liver cytochrome P-450 oxidation of arachidonic acid. Biochem Biophys Res Commun. 1982 Feb 11;104(3):916–922. doi: 10.1016/0006-291x(82)91336-5. [DOI] [PubMed] [Google Scholar]
- Falck J. R., Manna S., Moltz J., Chacos N., Capdevila J. Epoxyeicosatrienoic acids stimulate glucagon and insulin release from isolated rat pancreatic islets. Biochem Biophys Res Commun. 1983 Jul 29;114(2):743–749. doi: 10.1016/0006-291x(83)90843-4. [DOI] [PubMed] [Google Scholar]
- Fitzpatrick F. A., Ennis M. D., Baze M. E., Wynalda M. A., McGee J. E., Liggett W. F. Inhibition of cyclooxygenase activity and platelet aggregation by epoxyeicosatrienoic acids. Influence of stereochemistry. J Biol Chem. 1986 Nov 15;261(32):15334–15338. [PubMed] [Google Scholar]
- Frigerio A., Fanelli R., Biandrate P., Passerini G., Morselli P. L., Garattini S. Mass spectrometric characterization of carbamazepine-10,11-epoxide, a carbamazepine metabolite isolated from human urine. J Pharm Sci. 1972 Jul;61(7):1144–1147. doi: 10.1002/jps.2600610724. [DOI] [PubMed] [Google Scholar]
- Gray M. F., Lawrie T. D., Brooks C. J. Isolation and identification of cholesterol -oxide and other minor sterols in human serum. Lipids. 1971 Nov;6(11):836–843. doi: 10.1007/BF02531214. [DOI] [PubMed] [Google Scholar]
- Jung G., Yang D. C., Nakao A. Oxygenation of phosphatidylcholine by human polymorphonuclear leukocyte 15-lipoxygenase. Biochem Biophys Res Commun. 1985 Jul 31;130(2):559–566. doi: 10.1016/0006-291x(85)90453-x. [DOI] [PubMed] [Google Scholar]
- Kutsky P., Falck J. R., Weiss G. B., Manna S., Chacos N., Capdevila J. Effects of newly reported arachidonic acid metabolites on microsomal Ca++ binding, uptake and release. Prostaglandins. 1983 Jul;26(1):13–21. doi: 10.1016/0090-6980(83)90070-9. [DOI] [PubMed] [Google Scholar]
- Lapetina E. G., Billah M. M., Cuatrecasas P. The phosphatidylinositol cycle and the regulation of arachidonic acid production. Nature. 1981 Jul 23;292(5821):367–369. doi: 10.1038/292367a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oliw E. H., Guengerich F. P., Oates J. A. Oxygenation of arachidonic acid by hepatic monooxygenases. Isolation and metabolism of four epoxide intermediates. J Biol Chem. 1982 Apr 10;257(7):3771–3781. [PubMed] [Google Scholar]
- Samuelsson B. Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science. 1983 May 6;220(4597):568–575. doi: 10.1126/science.6301011. [DOI] [PubMed] [Google Scholar]
- Schwartzman M., Ferreri N. R., Carroll M. A., Songu-Mize E., McGiff J. C. Renal cytochrome P450-related arachidonate metabolite inhibits (Na+ + K+)ATPase. Nature. 1985 Apr 18;314(6012):620–622. doi: 10.1038/314620a0. [DOI] [PubMed] [Google Scholar]
- Sevanian A., Mead J. F., Stein R. A. Epoxides as products of lipid autoxidation in rat lungs. Lipids. 1979 Jul;14(7):634–643. doi: 10.1007/BF02533449. [DOI] [PubMed] [Google Scholar]
- Snyder G. D., Capdevila J., Chacos N., Manna S., Falck J. R. Action of luteinizing hormone-releasing hormone: involvement of novel arachidonic acid metabolites. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3504–3507. doi: 10.1073/pnas.80.11.3504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toto R., Siddhanta A., Manna S., Pramanik B., Falck J. R., Capdevila J. Arachidonic acid epoxygenase: detection of epoxyeicosatrienoic acids in human urine. Biochim Biophys Acta. 1987 Jun 2;919(2):132–139. doi: 10.1016/0005-2760(87)90199-8. [DOI] [PubMed] [Google Scholar]
- Wong P. Y., Westlund P., Hamberg M., Granström E., Chao P. H., Samuelsson B. 15-Lipoxygenase in human platelets. J Biol Chem. 1985 Aug 5;260(16):9162–9165. [PubMed] [Google Scholar]