Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Feb;79(3):767–770. doi: 10.1073/pnas.79.3.767

Cytochrome P-450-dependent oxygenation of arachidonic acid to hydroxyicosatetraenoic acids.

J Capdevila, L J Marnett, N Chacos, R A Prough, R W Estabrook
PMCID: PMC345833  PMID: 6801662

Abstract

Arachidonic acid is oxidized by a NADPH-dependent oxygenase of rat liver microsomes to a number of oxygen-containing products, which can be resolved by HPLC. Several of these products have been purified and characterized. They exhibit an absorbance in the UV region of the spectrum that has a maximum at approximately 235 nm, indicative of the presence of a conjugated diene function. Mass spectral analysis of the trimethylsilyl ether derivatives of the methyl esters of the hydrogenated and nonhydrogenated metabolites shows that they are the 9-, 11-, 12-, and 15-monohydroxy derivatives of arachidonic acid, the hydroxyicosatetraenoic acids (HETEs). Their UV absorbance and chromatographic properties suggest that these products possess cis,transdiene geometry characteristic of HETEs isolated from other mammalian sources. THe isolation of these isomeric HETEs suggests that cytochrome P-450 may play a role in the oxidative metabolism of arachidonic acid to physiologically and pharmacologically important hydroxylated unsaturated fatty acids.

Full text

PDF
767

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashley P. L., Griffin B. W. Involvement of radical species in the oxidation of aminopyrine and 4-aminoantipyrine by cumene hydroperoxide in rat liver microsomes. Mol Pharmacol. 1981 Jan;19(1):146–152. [PubMed] [Google Scholar]
  2. Boeynaems J. M., Brash A. R., Oates J. A., Hubbard W. C. Preparation and assay of monohydroxy-eicosatetraenoic acids. Anal Biochem. 1980 May 15;104(2):259–267. doi: 10.1016/0003-2697(80)90073-1. [DOI] [PubMed] [Google Scholar]
  3. Borgeat P., Samuelsson B. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A. 1979 May;76(5):2148–2152. doi: 10.1073/pnas.76.5.2148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  7. Fridovich S. E., Porter N. A. Oxidation of arachidonic acid in micelles by superoxide and hydrogen peroxide. J Biol Chem. 1981 Jan 10;256(1):260–265. [PubMed] [Google Scholar]
  8. Goetzl E. J., Sun F. F. Generation of unique mono-hydroxy-eicosatetraenoic acids from arachidonic acid by human neutrophils. J Exp Med. 1979 Aug 1;150(2):406–411. doi: 10.1084/jem.150.2.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hamberg M., Samuelsson B. On the specificity of the oxygenation of unsaturated fatty acids catalyzed by soybean lipoxidase. J Biol Chem. 1967 Nov 25;242(22):5329–5335. [PubMed] [Google Scholar]
  10. Hamberg M., Samuelsson B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3400–3404. doi: 10.1073/pnas.71.9.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hrycay E. G., O'Brien P. J. Cytochrome P-450 as a microsomal peroxidase utilizing a lipid peroxide substrate. Arch Biochem Biophys. 1971 Nov;147(1):14–27. doi: 10.1016/0003-9861(71)90304-3. [DOI] [PubMed] [Google Scholar]
  12. Lindgren J. A., Hansson G., Samuelsson B. Formation of novel hydroxylated eicosatetraenoic acids in preparations of human polymorphonuclear leukocytes. FEBS Lett. 1981 Jun 15;128(2):329–335. doi: 10.1016/0014-5793(81)80110-x. [DOI] [PubMed] [Google Scholar]
  13. Porter N. A., Wolf R. A., Yarbro E. M., Weenen H. The autoxidation of arachidonic acid: formation of the proposed SRS-A intermediate. Biochem Biophys Res Commun. 1979 Aug 28;89(4):1058–1064. doi: 10.1016/0006-291x(79)92115-6. [DOI] [PubMed] [Google Scholar]
  14. Roselló J., Gelpi E., Rigaud M., Durand J., Breton J. C. Quantitative profiling of the metabolic cascade of arachidonic acid by capillary gas chromatography mass spectrometry. Biomed Mass Spectrom. 1981 Apr;8(4):149–154. doi: 10.1002/bms.1200080404. [DOI] [PubMed] [Google Scholar]
  15. Walker I. C., Jones R. L., Wilson N. H. The identification of an epoxy-hydroxy acid as a product from the incubation of arachidonic acid with washed blood platelets. Prostaglandins. 1979 Aug;18(2):173–178. doi: 10.1016/0090-6980(79)90102-3. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES