title: On the nature of leukotriene C4 synthase in human platelets.
abstract: Leukotriene C4 is considered to play a major role in several important pathophysiological conditions, e.g., allergy, asthma, and shock. The present investigation demonstrates the presence in human platelets of a membrane-associated enzyme catalyzing the final step in the biosynthesis of leukotriene C4. This leukotriene C4 synthase was shown to be distinct from previously characterized "microsomal" and soluble glutathione transferases. The latter enzymes did not contribute significantly to the leukotriene A4 conjugating activity in platelets. As determined with leukotriene C4 synthase of a crude membrane fraction from human platelets, the Km value was 7 microM and the V value was 0.56 nmol x min-1 x mg-1 with leukotriene A4 as substrate. The enzyme was 20-fold more efficient with leukotriene A4 than with leukotriene A5 and 30-fold more efficient than with the unphysiological derivative leukotriene A4 methyl ester, as measured by the corresponding V/Km values; 14,15-leukotriene A4 was not a substrate. Platelets should be a useful source for the purification and further characterization of human leukotriene C4 synthase.
authors.affiliation: Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Söderström
authors.forename: B
authors.initials: B
authors.lastname: Mannervik
authors.forename: V
authors.initials: V
authors.lastname: Garkov
authors.forename: S
authors.initials: S
authors.lastname: Hammarström
mesh_terms: D001792:Blood Platelets / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D004795:Enzyme Stability; D005982:Glutathione Transferase / Q000097:blood*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D017572:Leukotriene A4; D015289:Leukotrienes / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D017572:Leukotriene A4; D015289:Leukotrienes; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase