Slow Reacting Substances (Leukotrienes): Enzymes Involved in Their Biosynthesis

• Published in: Proceedings of the National Academy of Sciences - PNAS 1982-08, Vol.79 (16), p.4838-4842
• Main Authors: Morris, Howard R., Taylor, Graham W., Jones, Claire M., Piper, Priscilla J., Samhoun, Marwa N., Tippins, John R.
• Format: Article
• Language: English
• Subjects: Animals; Basophils; Bioassay; Biochemistry; Biological Assay; Biosynthesis; Cell lines; Enzymes; gamma-Glutamyltransferase - metabolism; Glutathione Transferase - metabolism; Guinea Pigs; Homogenization; Ileum; Leukemia, Experimental - enzymology; Leukotrienes; Lung - enzymology; Lungs; Rats; Smooth muscle; SRS-A - biosynthesis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.79.16.4838

Slow reacting substances (leukotrienes C4, D4, E4) are synthesized in vivo by a combination of two previously unrelated pathways: lipoxygenase oxygenation of arachidonic acid and the glutathione detoxification pathway. Enzymes involved in the latter pathway (glutathione transferase [RX: glutathione R-transferase, EC 2.5.1.18]; γ -glutamyltransferase [(5-glutamyl)-peptide: amino acid 5-glutamyltransferase, EC 2.3.2.2]) have been investigated in guinea pig lung and rat basophilic leukemia (RBL-1) cells. We report data on levels of enzymic activity both before and during the release of slow reacting substances. Both glutathione transferase and γ -glutamyltransferase are present in significant quantities in guinea pig lung and RBL-1 cells. A model for the changes in γ -glutamyltransferase during leukotriene release is proposed for the cell line, and differences from the guinea pig lung system are reported. Leukotriene C4is converted to the more potent leukotriene D4by the action of γ -glutamyltransferase on guinea pig ileum during bioassay. γ -Glutamyltransferase may represent a control feature in the biosynthesis of leukotriene D4, and thus be involved in leukotriene-induced bronchoconstriction in the lung.