Leukotriene A4 Hydrolase: A Key Enzyme in the Biosynthesis of Leukotriene B4
LTA4 hydrolase (EC 220.127.116.11) catalyzes the conversion of the unstable epoxide intermediate LTA4 into the dihydroxy acid LTB4, 5(S), 12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid. Purified LTA4 hydrolase from human leukocytes was characterized as a monomeric enzyme (Mr ≈ 69,000) without cofactor requirement and distinct from other epoxide hydrolases (Rådmark et al., 1984). Since then, LTA4 hydrolase has been purified from a number of different cells and tissues, e.g., human erythrocytes (McGee and Fitzpatrick, 1985), human lung (Ohishi et al., 1987), the B-cell line Raji (Odlander et al., 1991), rat neutrophils (Evans et al., 1985), guinea pig lung (Bito et al., 1989), and guinea pig liver (Haeggström et al., 1988). The catalytic properties and physicochemical characteristics are similar for the different enzymes (for a review see Rådmark and Haeggström, 1990). Different methods, such as enzyme activity determinations and/or immunological detection, have shown that LTA4 hydrolase is widely distributed and the enzyme has been found in practically all cells, organs and tissues examined in man (Haeggström et al., 1985; Bigby et al., 1989; Fu et al., 1989), rat (Medina et al., 1988), and guinea pig (Izumi et al., 1986; Ohishi et al., 1990). The enzyme has been detected even in cells apparently devoid of 5-lipoxygenase activity and therefore unable to provide the substrate LTA4, e.g., erythrocytes (Fitzpatrick et al., 1984), T-cell lines (Fu et al, 1988), fibroblasts (Medina et al., 1990), endothelial cells (Claesson and Haeggström, 1988), keratinocytes (Iversen et al., 1993), and airway epithelial cells (Bigby et al., 1989; Bigby et al., 1994). Also cell free fluids such as blood plasma from several mammals (Fitzpatrick et al., 1983) and bronhoalveolar lavage fluid (Munafo et al., 1994) was found to exhibit LTA4 hydrolase activity.
KeywordsPeptidase Activity Wild Type Enzyme Epoxide Hydrolase Zinc Binding Human Polymorphonuclear Leukocyte
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