HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 41, 29890-29901, October 12, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/41/29890    most recent M703108200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yin, H. Articles by Morrow, J. D. Search for Related Content PubMed PubMed Citation Articles by Yin, H. Articles by Morrow, J. D. Social Bookmarking                      What's this?

Identification of Novel Autoxidation Products of the -3 Fatty Acid Eicosapentaenoic Acid in Vitro and in Vivo^*

Huiyong Yin, Joshua D. Brooks, Ling Gao¹, Ned A. Porter, and Jason D. Morrow²

From the Departments of Medicine and Pharmacology and Chemistry, Vanderbilt University, Nashville, Tennessee 37232

Increased intake of fish oil rich in the -3 fatty acids eicosapentaenoic acid (EPA, C20:5 -3) and docosahexaenoic acid (DHA, C22:6 -3) reduces the incidence of human disorders such as atherosclerotic cardiovascular disease. However, mechanisms that contribute to the beneficial effects of fish oil consumption are poorly understood. Mounting evidence suggests that oxidation products of EPA and DHA may be responsible, at least in part, for these benefits. Previously, we have defined the free radical-induced oxidation of arachidonic acid in vitro and in vivo and have proposed a unified mechanism for its peroxidation. We hypothesize that the oxidation of EPA can be rationally defined but would be predicted to be significantly more complex than arachidonate because of the fact that EPA contains an addition carbon-carbon double bond. Herein, we present, for the first time, a unified mechanism for the peroxidation of EPA. Novel oxidation products were identified employing state-of-the-art mass spectrometric techniques including Ag⁺ coordination ionspray and atmospheric pressure chemical ionization mass spectrometry. Predicted compounds detected both in vitro and in vivo included monocylic peroxides, serial cyclic peroxides, bicyclic endoperoxides, and dioxolane-endoperoxides. Systematic study of the peroxidation of EPA provides the basis to examine the role of specific oxidation products as mediators of the biological effects of fish oil.

Received for publication, April 12, 2007 , and in revised form, August 20, 2007.

^* This work was supported by National Institutes of Health Grants ES13125, ES000267, GM15431, ES31125, RR00096, DK48831, and CA77839. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Current address: Pharmaceutical Candidate Optimization, Discovery Metabolism, and Pharmacokinetics, Bristol-Myers Squibb, Route 206 and Provinceline Rd., Princeton, NJ 08540.

² To whom correspondence should be addressed: Division of Clinical Pharmacology, Depts. of Medicine and Pharmacology, Vanderbilt University School of Medicine, 532 RRB, 23^rd and Pierce Ave., Nashville, TN 37232-6602. Tel.: 615-343-1124; Fax: 615-322-3669; E-mail: Jason.morrow{at}vanderbilt.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. D. Brooks, G. L. Milne, H. Yin, S. C. Sanchez, N. A. Porter, and J. D. Morrow Formation of Highly Reactive Cyclopentenone Isoprostane Compounds (A3/J3-Isoprostanes) in Vivo from Eicosapentaenoic Acid J. Biol. Chem., May 2, 2008; 283(18): 12043 - 12055. [Abstract] [Full Text] [PDF]