Leukotriene C4/D4/E4/F4

Abstract

The leukotrienes C4, D4, E4 and F4 are a related group of amino acid substituted derivatives of leukotriene A4 produced by macrophages, basophils and mast cells. They are synthesized by conjugation with the tripeptide glutathione by glutathione-S-trans-ferase to produce the glutamyl-cysteinyl-glycyl derivative called leukotriene C4 (CAS 72025-60-6, M.Wt. 625.8). Metabolism proceeds by removal of the glutamic acid residue by γ-glutamyl-transpeptidase to produce leukotriene D4 (CAS 73836-78-9, M.Wt. 496.7) and then cleavage of the glycine residue by a dipeptidase to give the much less biologically active leukotriene E4 (CAS 75715-89-8, M.Wt. 439.6). The glutamic acid residue may be replaced on leukotriene E4 to produce the glutamyl-cysteinyl-derivative, leukotriene F4 (CAS 83851-42-7, M.Wt. 568.7). The leukotrienes C4, D4 and E4 are found as a mixture in variable proportions in the slow reacting substance of anaphylaxis (SRS-A) and are important local mediators of intermediate hypersensitivity reactions and inflammation. They are all potent broncho-constrictors but their relative potencies differ. For example, leukotriene D4 has a greater ability to induce plasma exudation whilst leukotriene C4 is a more powerful vasoconstrictor.