Arachidonate metabolism via lipoxygenase and 12L-hydroperoxy-5,8,10,14-icosatetraenoic acid peroxidase sensitive to anti-inflammatory drugs.
The enzymes of arachidonate metabolism via the lipoxygenase pathway in human platelet cytosol have been characterized and partially purified. The lipoxygenase activity has a pH optimum of 7.3 and reaches half-maximal activity at an arachidonate concentration of 80 microM. The oxidation of arachidonate by these enzymes is inhibited by reagents that modify sulfhydryl groups. Two separable lipoxygenase activities can be detected by chromatography of platelet cytosol on Sephadex G-150 and of partially purified preparations on DEAE-Sephadex. One of these has an apparent Mr of 100,000. A second enzyme species behaves as a Mr 160,000 entity containing, in addition to lipoxygenase, a peroxidase activity that catalyzes the conversion of 12L-hydroperoxy-5,8,10,14-icosatetraenoic acid (HPETE) to 12L-hydroxy-5,8,10,14-icosatetraenoic acid (HETE). Aspirin, indomethacin, sodium salicylate, phenylbutazone, ibuprofen, naproxen, and sulindac, but not acetaminophen or phenacetin, give rise to increased levels of HPETE in the lipoxygenase pathway. This increase in HPETE levels is the result of the ability of these drugs to inhibit directly the enzymatic conversion of HPETE to HETE.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D006801:Humans; D006880:Hydroxy Acids / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes; D008084:Lipoxygenase / Q000097:blood* / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D010544:Peroxidases / Q000097:blood; D012459:Salicylates / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D006880:Hydroxy Acids; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D012459:Salicylates; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C021201:12-HPETE; D010544:Peroxidases; D008084:Lipoxygenase; D001241:Aspirin; D007213:Indomethacin