Isolation of a new lipoxygenase metabolite of arachidonic acid, 8. 11, 12-trihydroxy-5,9,14-eicosatrienoic acid from human platelets.
Washed human platelets incubated with 1-14C-arachidonic acid (1mM) produced a new metabolite which migrated on thin layer chromatography close to thromboxane B2, but which was identified by mass spectrometry as a trihydroxy fatty acid. The mass spectrum was consistent with the assigned structure, 8,11,12-trihydroxy-5,9,14-eicosatrienoic acid (THETE). Platelet THETE synthesis from arachidonate was not inhibited by preincubation with asprin or indomethacin but was blocked by 5,8,11,14-eicosatetraynoic acid. Therefore, THETE appears to arise via the platelet lipoxygenase pathway rather than via the prostaglandin cyclooxygenase. Two proposed structures, including a novel dihydro-hydroxy-pyran cyclic intermediate, which could give rise to THETE are presented.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000302:isolation & purification*; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D005231:Fatty Acids, Unsaturated / Q000302:isolation & purification*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D015117:5,8,11,14-Eicosatetraynoic Acid; C019121:8,11,12-trihydroxy-5,9,14-eicosatrienoic acid; D008084:Lipoxygenase; D015126:8,11,14-Eicosatrienoic Acid; D001241:Aspirin; D007213:Indomethacin