Arachidonate metabolism via lipoxygenase and 12L-hydroperoxy-5,8,10,14-icosatetraenoic acid peroxidase sensitive to anti-inflammatory drugs.
- 1 January 1980
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 77 (1) , 308-312
- https://doi.org/10.1073/pnas.77.1.308
Abstract
The enzymes of arachidonate metabolism via the lipoxygenase pathway in human platelet cytosol were characterized and partially purified and the effects of antiinflammatory and/or analgesic drugs were examined. The lipoxygenase activity has a pH optimum of 7.3 and reaches half-maximal activity at an arachidonate concentration of 80 .mu.M. The oxidation of arachidonate by these enzymes is inhibited by reagents that modify sulfhydryl groups. Two separate 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 [molar fraction in exchanger phase] of 100,000. A 2nd enzyme species behaves as a Mr 160,000 entity containing, in addition to lipoxygenase, a peroxidase activity that catalyzes the conversion of 12 L-hydroperoxy-5,8,10,14-icosatetraenoic acid (HPETE) to 12 L-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.This publication has 37 references indexed in Scilit:
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