Interconversion of leukotrienes catalyzed by purified gamma-glutamyl transpeptidase: concomitant formation of leukotriene D4 and gamma-glutamyl amino acids.

The reversible conversion of leukotriene C4 to leukotriene D4 and of the latter to leukotriene E4 were studied with highly purified homogeneous preparations of gamma-glutamyl transpeptidase, dipeptidase, and aminopeptidase M. The conversion of leukotriene C4 to leukotriene D4, catalyzed by gamma-glutamyl transpeptidase, is significantly more rapid when carried out in the presence of an amino acid mixture a closely approximating that found in blood plasma and is accompanied by gamma-glutamyl amino acid formation. Because gamma-glutamyl transpeptidase is bound to the external surface of cell membranes and thus is readily accessible to plasma amino acids, it appears that conversion of leukotriene C4 to leukotriene D4 under physiological conditions is coupled with the formation of gamma-glutamyl amino acids. The apparent Km value for leukotriene C4 in this reaction is about 6 X 10(-6) M, a value close to that found for glutathione. Conversion of leukotriene D4 to leukotriene C4 is effectively catalyzed by gamma-glutamyl transpeptidase in the presence of relatively low concentrations of glutathione. The conversion of leukotriene D4 to leukotriene E4 is catalyzed much more rapidly by renal dipeptidase than by renal aminopeptidase M. Incubation of leukotriene E4 with gamma-glutamyl transpeptidase and glutathione leads to formation of a compound with the properties of gamma-glutamyl leukotriene E4; this reaction is analogous to that shown previously in which gamma-glutamyl cystine is formed by transpeptidation between glutathione and cystine.