Metabolism of 7,10,13,16-docosatetraenoic acid to dihomo-thromboxane, 14-hydroxy-7,10,12-nonadecatrienoic acid and hydroxy fatty acids by human platelets.
Human platelets metabolize 7,10,13,16-docosatetraenoic acid (22:4(n - 6)) into dihomo-thromboxane B2 and 14-hydroxy-7,10,12-nonadecatrienoic acid at about twenty percent of the rate they convert arachidonic acid to thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid. 14-Hydroxy-7,10,12,16-docosatetraenoic was the major metabolite produce via the lipoxygenase pathway. Several other hydroxy acids were also produced in small amounts via an indomethacin-insensitive pathway. Incubation of 20 microM arachidonic acid with various levels of 22:4(n - 6) resulted in a dose-dependent inhibition of both thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid production. Conversely, 12-hydroxy-5,8,10,14-eicosatetraenoic acid synthesis was stimulated because of substrate shunting to the lipoxygenase pathway. These results show that 22:4(n - 6) may modify platelet function both by serving as a precursor for a 22-carbon thromboxane and by suppressing the synthesis of thromboxane A2 from arachidonic acid. In addition, our results suggest that simultaneous release of 22:4(n - 6) and arachidonic acid from platelet phospholipids will result in an elevation of both 12-hydroxy-5,8,10,14-eicosatetraenoic acid levels as well as simultaneous synthesis of 14-hydroxy-7,10,12,16-docosatetraenoic acid.
D001792:Blood Platelets / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004883:Erucic Acids / Q000097:blood*; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006880:Hydroxy Acids / Q000097:blood*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood*; D013931:Thromboxanes / Q000097:blood*
D004883:Erucic Acids; D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids; D013931:Thromboxanes; C011395:adrenic acid; D013929:Thromboxane B2; C044591:1a,1b-dihomothromboxane B2; C044590:14-hydroxy-7,10,12-nonadecatrienoic acid