Leukotriene E4 elimination and metabolism in normal human subjects.

摘要: Radiolabeled leukotriene (LT) E4 was infused into three healthy subjects in order to assess the production and elimination of sulfidopeptide metabolites urine. Three different radiolabeled tracers were employed, [14,15-3H]LTE4, [35S]LTE4, [14C] LTE4 five separate infusion studies. There a rapid disappearance radioactivity from vascular compartment an apparent two-phase process. The first phase had half-life approximately 7 min. Radioactivity quickly appeared urine with 10-16% eliminated during 2 h following intravenous infusion; 7%, 2-5 h; 4%, 5-8 8-15 1.5%, 15-24 experiments. Unmetabolized major radioactive component collection, but at later times two more polar compounds predominated. After extensive purification by normal phase-solid extraction reverse-phase high performance liquid chromatography, these characterized UV spectroscopy, co-elution synthetic standards, negative ion electron capture gas chromatography/mass spectrometry, tandem mass spectrometry. urinary structurally determined be 14-carboxy-hexanor-LTE3 conjugated tetraene, 16-carboxy-delta 13-tetranor-LTE4. other minor detectable collection only standards as 16-carboxy-tetranor-LTE3, 18-carboxy-dinor-LTE4, 20-carboxy-LTE4. omega-Oxidation subsequent beta-oxidation methyl terminus metabolic fate for leukotrienes man. accumulation 14-COOH-LTE3 16-COOH-delta 13-LTE4 may reflect rate-limiting step further oxidation which places triene or respectively, carbons removed CoA ester moiety. Also there another metabolite identified N-acetyl-LTE4, however, no this observed. might useful assessing vivo humans.