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Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products.

Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. Research Abstract Details 

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  • Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. Abstract Text:

    masayuki wadaMasayuki Wada,cynthia j delongCynthia J DeLong,yu h hongYu H Hong,caroline j riekeCaroline J Rieke,inseok songInseok Song,ranjinder s sidhuRanjinder S Sidhu,chong yuanChong Yuan,mark warnockMark Warnock,alvin h schmaierAlvin H Schmaier,chieko yokoyamaChieko Yokoyama,emer m smythEmer M Smyth,stephen j wilsonStephen J Wilson,garret a fitzgeraldGarret A FitzGerald,r michael garavitoR Michael Garavito,de xin suiDe Xin Sui,john w reganJohn W Regan,william l smithWilliam L Smith,

    Dietary fish oil containing omega 3 highly unsaturated fatty acids has cardioprotective and anti-inflammatory effects. Prostaglandins (PGs) and thromboxanes are produced in vivo both from the omega 6 fatty acid arachidonic acid (AA) and the omega 3 fatty acid eicosapentaenoic acid (EPA). Certain beneficial effects of fish oil may result from altered PG metabolism resulting from increases in the EPA/AA ratios of precursor phospholipids. Here we report in vitro specificities of prostanoid enzymes and receptors toward EPA-derived, 3-series versus AA-derived, 2-series prostanoid substrates and products. The largest difference was seen with PG endoperoxide H synthase (PGHS)-1. Under optimal conditions purified PGHS-1 oxygenates EPA with only 10% of the efficiency of AA, and EPA significantly inhibits AA oxygenation by PGHS-1. Two- to 3-fold higher activities or potencies with 2-series versus 3-series compounds were observed with PGHS-2, PGD synthases, microsomal PGE synthase-1 and EP1, EP2, EP3, and FP receptors. Our most surprising observation was that AA oxygenation by PGHS-2 is only modestly inhibited by EPA (i.e. PGHS-2 exhibits a marked preference for AA when EPA and AA are tested together). Also unexpectedly, TxA(3) is about equipotent to TxA(2) at the TP alpha receptor. Our biochemical data predict that increasing phospholipid EPA/AA ratios in cells would dampen prostanoid signaling with the largest effects being on PGHS-1 pathways involving PGD, PGE, and PGF. Production of 2-series prostanoids from AA by PGHS-2 would be expected to decrease in proportion to the compensatory decrease in the AA content of phospholipids that would result from increased incorporation of omega 3 fatty acids such as EPA.

    Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. Publishing Authors By Initials

    m wadaM Wada,cj delongCJ DeLong,yh hongYH Hong,cj riekeCJ Rieke,i songI Song,rs sidhuRS Sidhu,c yuanC Yuan,m warnockM Warnock,ah schmaierAH Schmaier,c yokoyamaC Yokoyama,em smythEM Smyth,sj wilsonSJ Wilson,ga fitzgeraldGA FitzGerald,rm garavitoRM Garavito,de x suide X Sui,jw reganJW Regan,wl smithWL Smith,

    For similar thromboxanes research abstracts see: thromboxanes research

    PUBMED ID PMID:

    MEDLINE DATE:

    Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: The Journal of biological chemistry

    VOLUME: 282

    Page Numbers: 22254-66

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 22

    MONTH: 05

    YEAR: 2007

    Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2985121

    Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. Keywords Mesh Terms:

    KEYWORDS: Thromboxanes

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. Information

    Substance Name: thromboxane A3

    Registry Number: 60114-68-3

    Grant and Affiliation Information for Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products.

    AFFILIATION: Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NHLBI

    GRANT: HL56773

    ACRONYM: HL

    MEDLINETA: J Biol Chem

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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