Aspirin-like drugs interfere with arachidonate metabolism by inhibition of the 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid peroxidase activity of the lipoxygenase pathway.
نویسندگان
چکیده
Aspirin, indomethacin, and sodium salicylate are anti-inflammatory, analgesic, and antipyretic. Whereas aspirin and indomethacin inhibit prostaglandin synthetase (cyclo-oxygenase; 8,11,14-eicosatrienoate, hydrogen-donor: oxygen oxidoreductase, EC 1.14.99.1), salicylate does not. However, all three drugs affect the metabolism of arachidonate via the lipoxygenase pathway by inhibiting the conversion of 12-hydroperoxy- to 12-hydroxy-5,8,10,14-eicosatetraenoic acid.
منابع مشابه
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 lipoxyg...
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12-Lipoxygenases oxygenate arachidonic acid producing its 12S-hydroperoxy derivative and are well known as platelet and leukocyte enzymes. When a peroxidase-linked immunoassay of the enzyme according to the avidin-biotin method was applied to the cytosol fractions from various parts of porcine brain, a considerable amount of the enzyme was found in the anterior pituitary. The enzyme level (abou...
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Arachidonate 5-lipoxygenase was purified to near homogeneity from the 105,000 X g supernatant of porcine leukocyte homogenate by immunoaffinity chromatography using a monoclonal anti-5-lipoxygenase antibody. Reaction of the purified enzyme with arachidonic acid produced predominantly 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid with concomitant formation of several more polar compounds in smal...
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A homogenate of epidermal cells isolated from human skin converted arachidonic acid to 12S-hydroxy-5, 8,10,14-eicosatetraenoic acid and 15-hydroxy-5, 8,11,13-eicosatetraenoic acid as the main lipoxygenase products. The production of these hydroxy acids was not stimulated by the addition of 1 mM NADPH required for cytochrome P-450 reaction, but inhibited by 65-75% with 40 microM nordihydroguaiar...
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عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 76 8 شماره
صفحات -
تاریخ انتشار 1979