The enzyme glutathione peroxidase in arachidonic acid metabolism of human platelets.

We investigated the possible regulatory role of glutathione peroxidase on thromboxane formation by reducing peroxides in platelets. Experiments carried out in platelet lysates demonstrated that the burst of the arachidonate metabolism was accompanied by a simultaneous burst of hydrogen transfer from glutathione to peroxides, catalyzed by endogenous glutathione peroxidase. The burst of hydrogen transfer was partially inhibited by acetylsalicylate concurrently with the complete inhibition of malondialdehyde formation, thus suggesting that the hydrogen acceptor peroxides were derived in part from the cyclooxygenase pathway. Moreover, increasing glutathione peroxidase activity by adding purified enzyme to the incubation media decreases thromboxane formation. Intact platelets, stimulated with arachidonic acid or thrombin, produced malondialdehyde and thromboxane in amounts roughly inversely related to the endogenous glutathione peroxidase activity. In contrast, no correlation was observed between glutathione peroxidase activity and agonist-induced platelet aggregation. Our experiments suggest that in normal platelets, glutathione peroxidase controls thromboxane formation.