Inhibition of platelet thromboxane synthetase by L-1-tosylamido-2-phenylethyl chloromethyl ketone.
L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK) was found to inhibit several aspects of arachidonic acid (20:4) metabolism in human platelets; the primary effect being inhibition of thromboxane synthetase. Thromboxane B2 (TxB2) formation from exogenous 20:4 or PGH2, or from endogenous 20:4, was inhibited by TPCK at concentrations between 0.1 and 0.5 mM. Formation of malondialdehyde (MDA) and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT), products which also arise from PGH2, was inhibited to a similar extent. Inhibition of formation from 20:4 of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), the product of the lipoxygenase pathway, was observed; although the extent of this inhibition was less than that of TxB2 formation. A small inhibitory effect of TPCK on the release of 20:4 from platelet phospholipids was also observed. This evidence indicated that while a number of reactions are inhibited by TPCK, the primary effect appears to be inhibition of thromboxane synthetase.
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008315:Malondialdehyde / Q000097:blood; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011463:Prostaglandins H / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology*
D000590:Amino Acid Chloromethyl Ketones; D001095:Arachidonic Acids; D011463:Prostaglandins H; D014108:Tosylphenylalanyl Chloromethyl Ketone; D008315:Malondialdehyde; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase