On the mechanism of biosynthesis of leukotrienes and related compounds.
[10D-3H; 3-14C]- and [10L-3H; 3-14C]arachidonic acids were incubated with human polymorphonuclear leukocytes and with human platelets. Leukotriene B4 and 5(S),12(S)-dihydroxy-6trans,8cis,10trans,14-cis-eicosatetraenoic acid (5,12-DHETE) were isolated and the 3H/14C ratios determined. It could be concluded that the 10D (pro-R)-hydrogen is eliminated in the conversion of 5(S)-hydroperoxy-6trans,8-cis,11cis,14cis-eicosatetraenoic acid into leukotriene A4 whereas in the conversion of arachidonic acid into 5,12-DHETE the 10L (pro-S)-hydrogen is lost. Incubation of the doubly labeled arachidonic acids with human platelets confirmed and extended previous data on the stereochemistry of the hydrogen removal from C-10 during the conversion into 12(S)-hydroperoxy-5cis,8cis,10trans,14cis-eicosatetraenoic acid, i.e., the 10L (pro-S)-hydrogen is eliminated and the 10D (pro-R)-hydrogen retained.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis* / Q000097:blood; D009504:Neutrophils / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood; D014316:Tritium
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D014316:Tritium; D007975:Leukotriene B4; D016718:Arachidonic Acid; D013929:Thromboxane B2