A short-chain aldehyde is a major lipoxygenase product in arachidonic acid-stimulated porcine leukocytes.
Porcine leukocytes convert exogenous arachidonic acid to a complex array of products derived via the 5-, 12-, and 15-lipoxygenase pathways of metabolism. The major monohydroxylated metabolite following addition of 100 microM arachidonic acid is 12-hydroxyeicosatetraenoic acid. Of the more polar compounds on reverse-phase high pressure liquid chromatography, the most prominent is a previously uncharacterized arachidonate product which chromatographs near to the omega-oxidized metabolites of leukotriene B4. The structure of this new product was examined by high pressure liquid chromatography, UV, NMR, and also by gas chromatography-mass spectrometry of several derivatives; it was identified as 12-oxododeca-5,8,10-(Z,Z,E)-trienoic acid. It is proposed that this C-12 trienal acid is formed from 12-hydroperoxyeicosatetraenoic acid by a cleavage reaction catalyzed by the leukocyte 12-lipoxygenase in the presence of excess arachidonic acid and under anaerobic conditions. These conditions are satisfied by addition of 100 microM arachidonic acid to the leukocyte suspension (3 X 10(7) cells/ml); 12-hydroperoxyeicosatetraenoic acid is formed as the major product, excess arachidonic acid is available, and the concomitant leukocyte respiratory burst quickly depletes the solution of oxygen. Preliminary experiments indicate that this aldehyde product has significant biological activity in the activation of leukocytes. In the course of an intense inflammatory reaction it is conceivable that the conditions for synthesis of this C-12 trienal acid and related aldehydes could prevail; such aldehydes would constitute an additional class of lipoxygenase product which exacerbates the process of inflammation.
Glasgow
W C
WC
Harris
T M
TM
Brash
A R
AR
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010100:Oxygen; D013056:Spectrophotometry, Ultraviolet; D013552:Swine
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D010100:Oxygen