Enzymes involved in the biosynthesis of leukotriene B4

Abstract

Ten years have elapsed since the discovery and structural elucidation of the leukotriene compounds (1-5). The leukotrienes constitute a group of potent biologically active arachidonic acid-derived metabolites which are implicated as mediators of immediate hypersensitivity reactions and inflammation. They were first discovered in leukocytes and were determined to contain a conjugated triene structure, thus the derivation of their name (6). The cysteinyl-containing leukotrienes (LTC,, LTD4, and LTE,),' which together make up the slow reacting substance of anaphylaxis, are synthesized primarily by eosinophils, mast cells, and macrophages. They stimulate contraction of various smooth muscle cells, promote bronchial mucous secretion, and induce extravasation of plasma proteins by increasing microvascular permeability. Leukotriene B, (LTB,), synthesized predominantly by neutrophils, is capable of stimulating circulating leukocytes to adhere to the vascular endothelium and induces extravasation and chemotaxis of polymorphonuclear leukocytes in nanomolar concentrations. At higher concentrations, LTBI induces polymorphonuclear leukocyte degranulation, superoxide generation, and can augment natural killer cell activity. Several reviews on the structure, biosynthesis, and biological actions of the leukotrienes have been written (7-13). It is the aim of the present review to concentrate on the advances made in recent years, primarily through molecular biology studies, on the reaction pathway leading to production of LTB,. 5-Lipoxygenase