Work

The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology.

Year: 1984

Type: review

Abstract: Tbiological activity of one major class of leukotrienes, originally described as slow reacting substance of anaphylaxis (SRS-A)' (1, 2) and now known to be composed of the sulfidopeptide leukotrienes, 5S-hydroxy-6R-S-glutathionyl-7,9-trans-I 1, 14-cis-eicosatetraenoic acid (leukotriene C4, LTC4), 5S-hydroxy-6R-S-cysteinylglycyl-7,9-trans-11, 14-cis-eicosa- tetraenoic acid (leukotriene D4, LTD4), and 5S-hydroxy-6R-Scysteinyl-7,9-trans-1 1, 14-cis-eicosatetraenoic acid (leukotriene E4, LTE4) (3-7), has been known for over 40 years.The biological activity and structure of the second major class of leukotrienes, represented solely by 5S-12R-dihydroxy-6,14-cis-8, I0-trans- eicosatetraenoic acid (leukotriene B4, LTB4), was recognized only 5 years ago (8-11).On the basis of the earlier definition of SRS-A in terms ofchromatographic, functional, and chemical characteristics (12-15), it was possible to generate a similar material with radiolabeled constituents by ionophore activation of mouse mastocytoma cells and to achieve a chemical characterization of LTC4 (3).The stereospecific synthesis of both LTC4 (16) and LTB4 (17) has now permitted the delineation of the common and separate enzymes in the pathways for biosynthesis of LTC4 and LTB4 from arachidonic acid (reviewed Receivedfor publication I December 1983.1. Abbreviations used in this paper: 5-HPETE, 5S-hydroperoxy-6-trans-8,1 1,14-cis-eicosatetraenoic acid; LTA4, 5,6-trans-oxido-7,9-trans-1 1,14cis-eicosatetraenoic acid; LTB4, 5S-12R-dihydroxy-6,14-cis-8, 10-transeicosatetraenoic acid; LTC4, 5S-hydroxy-6R-S-glutathionyl-7,9-trans-1 1,14-cis-eicosatetraenoic acid; LTD4, 5S-hydroxy-6R-S-cysteinylglycyl- 7,9-trans-I 1,14-cis-eicosatetraenoic acid; LTE4, 5S-hydroxy-6R-S-cysteinyl-7,9-trans-1 1, 14-cis-eicosatetraenoic acid; LTB5, 5,12-dihydroxy-6,8,10,14,17-eicosapentaenoic acid; LTC5, 5-hydroxy-6-S-glutathionyl-7,9-trans-i 1,14,17-cis-eicosapentaenoic acid; PMN, peripheral blood polymorphonuclear neutrophilic leukocytes; RP-HPLC, reverse phasehigh performance liquid chromatography; SRS-A, slow reacting substance of anaphylaxis.

Source: Journal of Clinical Investigation

DOI: 10.1172/jci111312

Authors: R A Lewis, K F Austen

Institutions: Brigham and Women's Hospital, Harvard University

Language: English

Topic: Eicosanoids and Hypertension Pharmacology

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: National Institutes of Health