Transport of gamma-glutamyl amino acids: role of glutathione and gamma-glutamyl transpeptidase.

Abstract

This work relates to the hypothesis that 1 of the mechanisms that mediates amino acid translocation across cell membranes involves the action of membrane-bound .gamma.-glutamyl transpeptidase on intracellular glutathione and extracellular amino acids to form .gamma.-glutamyl amino acids. The latter are thought to be translocated into the cell where the .gamma.-glutamyl moiety is removed to yield free amino acids. Previous studies showed that intracellular glutathione is translocated out of many cells. The transport of .gamma.-glutamyl amino acids into tissues was examined in the mouse by use of the model substrate L-.gamma.-glutamyl-L-[14C]methionine sulfone. Of 11 tissues examined, only the kidney showed strong and preferential uptake of the substrate. A substantial amount of the administered L-.gamma.-glutamyl-L-[14C]methionine sulfone was intact in the kidney; the total uptake of this compound was greater (by about 2-fold) than that of free L-methionine sulfone. Studies with other .gamma.-glutamyl amino acids and .gamma.-glutamyl compounds indicate that the kidney has a relatively specific transport system for .gamma.-glutamyl amino acids. Small, but significant amounts of .gamma.-glutamylmethionine sulfone were found in the liver and pancreas, suggesting that other tissues may also have this system. Transport of .gamma.-glutamylmethionine sulfone into the kidney was inhibited by inhibitors of glutathione synthesis and of .gamma.-glutamyl transpeptidase. Results suggest that both transpeptidase and glutathione may be involved in transport of .gamma.-glutamyl amino acids.