Biosynthesis of thromboxane B2 and 12-L-hydroxy-5,8,10-heptadecatrienoic acid in human platelets. Evidence for a common enzymatic pathway.
Human platelet microsomes convert prostaglandin H2 to thromboxane B2 and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (12OH-17:3) in approximately equimolar amounts. The synthesizing activities of both products appear to go in parallel, both activities gradually decline upon storage and are equally destroyed by heat inactivation. Furthermore imidazole, a potent inhibitor of thromboxane synthetase activity, is an equally effective inhibitor of 12OH-17:3 formation in platelets. These results suggest that both thromboxane B2 and 120H-17:3 are derived from a common intermediate. We propose two alternative pathways for the conversion of prostaglandin H2 to thromboxane A2 and 12OH-17:3 in human platelets. The first pathway depicts thromboxane A2 as the common intermediate for the formation of both thromboxane B2 and 12OH-17:3. In the second pathway, prostaglanding H2 is converted to an activated intermediate which is converted to either thromboxane A2 or 12OH-17:3.
D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D006880:Hydroxy Acids / Q000096:biosynthesis*; D007093:Imidazoles / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D010974:Platelet Aggregation; D011453:Prostaglandins / Q000096:biosynthesis; D011463:Prostaglandins H / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism*
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids; D007093:Imidazoles; D011453:Prostaglandins; D011463:Prostaglandins H; D013931:Thromboxanes; D008315:Malondialdehyde; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase