Harpers

METABOLISM OF UNSATURATED FATTY ACIDS & EICOSANOIDS / 193DietMembrane phospholipidLinoleate–2HPHOSPHOLIPASEA 2+Angiotensin IIBradykininEpinephrineThrombinγ-Linolenate+2C8,11,14-Eicosatrienoate(dihomo γ-linolenate)COOH12GROUP 1ProstanoidsPGE 1PGF 1TXA 1LeukotrienesLTA 3LTC 3LTD 3–2HDiet GROUP 2ProstanoidsPGD 21PGE 2PGFCOOH2PGI 2TXA 25,8,11,14-EicosatetraenoateArachidonate2LeukotrienesLTA 4LTB 4LTC 4LTD 4LTE 4LipoxinsLXA 4LXB 4LXC 4LXD 4LXE 4–2HEicosatetraenoate+2COctadecatetraenoate5,8,11,14,17-EicosapentaenoateCOOH12GROUP 3ProstanoidsPGD 3PGE 3PGF 3PGI 3TXA 3LeukotrienesLTA 5LTB 5LTC 5–2HDietα-LinolenateDietFigure 23–5. The three groups of eicosanoids and their biosynthetic origins. (PG, prostaglandin; PGI, prostacyclin;TX, thromboxane; LT, leukotriene; LX, lipoxin; 1 , cyclooxygenase pathway; 2 , lipoxygenase pathway.)The subscript denotes the total number of double bonds in the molecule and the series to which the compoundbelongs.(TXA 2 ) and prostacyclin (PGI 2 ). Each cell type producesonly one type of prostanoid. Aspirin, a nonsteroidalanti-inflammatory drug (NSAID), inhibits cyclooxygenaseof both PGHS-1 and PGHS-2 byacetylation. Most other NSAIDs, such as indomethacinand ibuprofen, inhibit cyclooxygenases by competingwith arachidonate. Transcription of PGHS-2—but notof PGHS-1—is completely inhibited by anti-inflammatorycorticosteroids.Essential Fatty Acids Do Not ExertAll Their Physiologic Effects ViaProstaglandin SynthesisThe role of essential fatty acids in membrane formationis unrelated to prostaglandin formation. Prostaglandinsdo not relieve symptoms of essential fatty acid deficiency,and an essential fatty acid deficiency is notcaused by inhibition of prostaglandin synthesis.