Metabolism of leukotriene C3 in the guinea pig. Identification of metabolites formed by lung, liver, and kidney.

[5,6,8,9,11,12-3H6]Leukotriene C3 was converted to polar metabolites which ere excreted in feces and urine for 4-5 days after subcutaneous administration to guinea pigs. Lung homogenates converted leukotriene C3 to leukotriene D3. Liver and kidney homogenates did not catabolize leukotriene C3 appreciably due to inhibition of gamma-glutamyl transpeptidase in these tissues by endogenous glutathione. Liver and kidney homogenates metabolized [3H6]leukotriene D3 to the cysteine analog, leukotriene E3 (Bernström, K., and Hammarström, S. (1981) J. Biol. Chem. 256, 9579-9582). In addition leukotriene C3 and products of greater polarity were formed. The conversion of leukotriene D3 to leukotriene C3 was catalyzed by gamma-glutamyl transpeptidase which performed a reverse reaction due to the high tissue concentrations of glutathione. The results suggest that the degradation of leukotriene C3 to leukotriene D3 is important for the further metabolism of this leukotriene in liver and kidney.