The Fats of Life: Essential Fatty Acids in Health and Disease

Appendix C. Chemical Structures of Eicosanoids

222 222 APPENDIX C. CHEMICAL STRUCTURES OF EICOSANOIDS FIGURE C.1. Eicosanoids synthesized from arachidonic acid, the major omega-6 twenty-carbon polyunsaturated fatty acid. 12-HPETE CH3 COOH HOO 12-HETE COOH HO 15-HETE COOH OH CH3 S cys COOH LTE4 12-Lipoxygenase 15-HPETE COOH OOH S cys-gly COOH LTD4 Arachidonic Acid COOH OH LTB4 OH COOH 5-HETE COOH 5-HPETE COOH OOH LTA4 5-Lipoxygenase OH S cys-gly COOH LTC5 gamma-glu OH Cyclooxygenase (COX) PGE2 PGF2alpha OH COOH OH O OH COOH O OH OH COOH OH OH PGD2 HO O COOH PGI2 (Prostacyclin) CH3 CH3 OH CH3 CH3 CH3 CH3 CH3 CH3 COOH O CH3 CH3 O O OOH COOH PGG2 CH3 O O OH COOH PGH2 CH3 OH COOH O O TXA2 CH3 CH3 CH3 CH3 CH3 15-Lipoxygenase FIGURE C.2. Eicosanoids synthesized from eicosapentaenoic acid (EPA), an omega-3 twenty-carbon polyunsaturated fatty acid. CHEMICAL STRUCTURES OF EICOSANOIDS 223 12-HPEPE CH3 COOH HOO 12-HEPE CH3 COOH HO 15-HEPE CH3 COOH OH CH3 S gly LTE5 12-Lipoxygenase 15-HPEPE CH3 COOH OOH CH3 S cys-gly LTD5 EPA Eicosapentaenoic Acid COOH OH CH3 LTB OH COOH CH3 5-HEPE COOH CH3 5-HPEPE COOH CH3 OOH LTA5 COOH CH3 O 15-Lipoxygenase OH CH3 S cys-gly COOH LTC5 gamma-glu OH O O OOH CH3 COOH Cyclooxygenase (COX) O O OH CH3 COOH PGG3 PGH3 OH CH3 COOH O O TXA3 PGH3 PGF3alpha OOH CH3 COOH OH O OH CH3 COOH O OH OH CH3 COOH OH OH PGD3 HO O COOH CH3 PGI3 COOH OH COOH OH 5-Lipoxygenase APPENDIX C 224 FIGURE C.3. Eicosanoids synthesized from dihomo-gamma-linolenic acid (DHGLA), a minor omega-6 twenty-carbon polyunsaturated fatty acid. 12-Hydroperoxyeicosatrienoic acid 12-Hydroxyeicosatrienoic acid 15-Hydroxyeicosatrienoic acid 12-Lipoxygenase Dihomo-gammalinolenic acid (DHGLA) Cyclooxygenase (COX) COOH HO CH3 COOH OH CH3 COOH CH3 CH3 COOH HOO 15-Hydroperoxytrienoic acid COOH OOH CH3 O O OOH COOH PGG1 CH3 O O OH COOH PGH1 CH3 OH O O TXA1 CH3 COOH OH OH O PGD1 CH3 COOH PGE1 OH O OH CH3 COOH PGF1a OH OH OH CH3 COOH No PGI formed Note: DHGLA can inhibit metabolism of arachiconic acid by these enzymes when released from membrane phospholipids . DHGLA is also metabolized to arachidonic acid 5-Lipoxygenase No 5-Lipoxygenase product formed and no leukotrienes 15-Lipoxygenase ...