Stereospecific elimination of hydrogen at C-10 in eicosapentaenoic acid during the conversion to leukotriene C5.
(10L)- and (10D)-[1-14C, 10-3H]5,8,11,14,17-eicosapentaenoic acids were synthesized to investigate mechanistic and stereochemical aspects of leukotriene biosynthesis. Experiments with mastocytoma cells showed that a hydrogen is stereospecifically eliminated from C-10 during the conversion of eicosapentaenoic acid to leukotriene C5. The hydrogen lost has the pro-S (D) configuration. 5-Hydroxy-6,8,11,14,17-eicosapentaenoic acid, formed in the same experiments, was enriched in tritium when the (10D), but not when the (10L), isomer of labeled eicosapentaenoic acid was used. This indicates that oxygenation of the acid at C-5 occurred before the elimination of hydrogen and suggests that removal of the pro-S hydrogen at C-10 in 5-hydroperoxy-6,8,11,14,17-eicosapentaenoic acid initiates its transformation to trans-5(S),6(S)-oxido-7,9-trans-11,14,17-cis-eicosapentaenoic acid (leukotriene A5).
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002250:Carbon Radioisotopes; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000378:metabolism*; D006801:Humans; D012515:Mast-Cell Sarcoma / Q000378:metabolism*; D051379:Mice; D013189:SRS-A / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D012513:Sarcoma, Experimental / Q000378:metabolism*; D014316:Tritium
D002250:Carbon Radioisotopes; D005231:Fatty Acids, Unsaturated; D013189:SRS-A; D014316:Tritium; C026144:leukotriene C-5; D015118:Eicosapentaenoic Acid