Leukotriene E4 elimination and metabolism in normal human subjects - PubMed (original) (raw)
. 1990 Dec 15;265(35):21771-8.
Affiliations
- PMID: 2174886
Free article
Leukotriene E4 elimination and metabolism in normal human subjects
A Sala et al. J Biol Chem. 1990.
Free article
Abstract
Radiolabeled leukotriene (LT) E4 was infused into three healthy subjects in order to assess the production and elimination of sulfidopeptide leukotriene metabolites in urine. Three different radiolabeled tracers were employed, [14,15-3H]LTE4, [35S]LTE4, and [14C] LTE4 in five separate infusion studies. There was a rapid disappearance of radioactivity from the vascular compartment in an apparent two-phase process. The first elimination phase had an apparent half-life of approximately 7 min. Radioactivity quickly appeared in the urine with 10-16% eliminated during the first 2 h following intravenous infusion; 7%, 2-5 h; 4%, 5-8 h; 4%, 8-15 h; and 1.5%, 15-24 h from the [14C] LTE4 experiments. Unmetabolized LTE4 was the major radioactive component in the first urine collection, but at later times two more polar compounds predominated. After extensive purification by normal phase-solid phase extraction and reverse-phase high performance liquid chromatography, these compounds were characterized by UV spectroscopy, co-elution with synthetic standards, negative ion electron capture gas chromatography/mass spectrometry, and tandem mass spectrometry. The two major urinary metabolites were structurally determined to be 14-carboxy-hexanor-LTE3 and the conjugated tetraene, 16-carboxy-delta 13-tetranor-LTE4. Three other minor metabolites were detectable in the first urine collection only and were characterized by co-elution with synthetic standards as 16-carboxy-tetranor-LTE3, 18-carboxy-dinor-LTE4, and 20-carboxy-LTE4. omega-Oxidation and subsequent beta-oxidation from the methyl terminus appeared to be the major metabolic fate for sulfidopeptide leukotrienes in man. The accumulation of the 14-COOH-LTE3 and 16-COOH-delta 13-LTE4 may reflect a rate-limiting step in further oxidation of these compounds which places a conjugated triene or conjugated tetraene, respectively, two carbons removed from the CoA ester moiety. Also in the first urine collection there was another minor metabolite identified as N-acetyl-LTE4, however, no subsequent beta-oxidation of this metabolite was observed. The major metabolites of LTE4 might be useful in assessing in vivo production of sulfidopeptide leukotrienes in humans.
Similar articles
- Metabolism of cysteinyl leukotrienes in monkey and man.
Huber M, Müller J, Leier I, Jedlitschky G, Ball HA, Moore KP, Taylor GW, Williams R, Keppler D. Huber M, et al. Eur J Biochem. 1990 Nov 26;194(1):309-15. doi: 10.1111/j.1432-1033.1990.tb19458.x. Eur J Biochem. 1990. PMID: 2174780 - Peroxisomal degradation of leukotrienes by beta-oxidation from the omega-end.
Jedlitschky G, Huber M, Völkl A, Müller M, Leier I, Müller J, Lehmann WD, Fahimi HD, Keppler D. Jedlitschky G, et al. J Biol Chem. 1991 Dec 25;266(36):24763-72. J Biol Chem. 1991. PMID: 1761571 - Entry rate and metabolism of leukotriene C4 into vascular compartment in healthy subjects.
Maclouf J, Antoine C, De Caterina R, Sicari R, Murphy RC, Patrignani P, Loizzo S, Patrono C. Maclouf J, et al. Am J Physiol. 1992 Jul;263(1 Pt 2):H244-9. doi: 10.1152/ajpheart.1992.263.1.H244. Am J Physiol. 1992. PMID: 1322060 Clinical Trial. - Metabolism of leukotrienes.
Hammarström S, Orning L, Bernström K. Hammarström S, et al. Mol Cell Biochem. 1985 Nov;69(1):7-16. doi: 10.1007/BF00225922. Mol Cell Biochem. 1985. PMID: 3001504 Review.
Cited by
- Lipid droplets and lipid mediators in viral infection and immunity.
Monson EA, Trenerry AM, Laws JL, Mackenzie JM, Helbig KJ. Monson EA, et al. FEMS Microbiol Rev. 2021 Aug 17;45(4):fuaa066. doi: 10.1093/femsre/fuaa066. FEMS Microbiol Rev. 2021. PMID: 33512504 Free PMC article. Review. - A Novel Strategy to Mitigate the Hyperinflammatory Response to COVID-19 by Targeting Leukotrienes.
Funk CD, Ardakani A. Funk CD, et al. Front Pharmacol. 2020 Aug 6;11:1214. doi: 10.3389/fphar.2020.01214. eCollection 2020. Front Pharmacol. 2020. PMID: 32848802 Free PMC article. - Use of high-resolution metabolomics for the identification of metabolic signals associated with traffic-related air pollution.
Liang D, Moutinho JL, Golan R, Yu T, Ladva CN, Niedzwiecki M, Walker DI, Sarnat SE, Chang HH, Greenwald R, Jones DP, Russell AG, Sarnat JA. Liang D, et al. Environ Int. 2018 Nov;120:145-154. doi: 10.1016/j.envint.2018.07.044. Epub 2018 Aug 7. Environ Int. 2018. PMID: 30092452 Free PMC article. - Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines.
Salimi M, Stöger L, Liu W, Go S, Pavord I, Klenerman P, Ogg G, Xue L. Salimi M, et al. J Allergy Clin Immunol. 2017 Oct;140(4):1090-1100.e11. doi: 10.1016/j.jaci.2016.12.958. Epub 2017 Jan 20. J Allergy Clin Immunol. 2017. PMID: 28115217 Free PMC article. - Leukotriene E4 elicits respiratory epithelial cell mucin release through the G-protein-coupled receptor, GPR99.
Bankova LG, Lai J, Yoshimoto E, Boyce JA, Austen KF, Kanaoka Y, Barrett NA. Bankova LG, et al. Proc Natl Acad Sci U S A. 2016 May 31;113(22):6242-7. doi: 10.1073/pnas.1605957113. Epub 2016 May 16. Proc Natl Acad Sci U S A. 2016. PMID: 27185938 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources