No abstract

Rat liver contains a high concentration (7-8mM) of reduced glutathione and its level changes rapidly when starving or feeding rats. We concluded that one of the functions of liver glutathione was to act as a reservoir of cysteine. When starved rats were fed a protein-free diet, the increase in liver glutathione was dependent on the amount of cysteine added to the diet. A cysteine-dependent increase of glutathione was also observed in rats fed a diet containing gelatin with cysteine, but the increase was relatively lowered compared with rats fed a protein-free diet containing the same amount of cysteine. This suppression of the increase in glutathione was observed much more clearly when the gelatin diet was fortified with tryptophan in addition to cysteine. In the presence of tryptophan, L-[35S]-cysteine in the diet appeared to be incorporated primarily into liver and serum proteins, and degradation of liver glutathione must also have been enhanced. Addition of excess cysteine to the diet masked the effects of gelatin and tryptophan, stimulated glutathione synthesis in the liver as well as incorporation of dietary cysteine into protein fractions. Prolonged starvation of rats or injection of dibutyryl-3',5'-cyclic AMP lowered the glutathione level,but the level did not decrease below 2 to 3 mM. These findings suggest that there may be at least two pools of glutathione. A labile fraction, constituting one-third to one-half the total liver glutathione, probably serves as a reservoir of cysteine which can be released by gamma-glutamyl-transferase when necessary.

No abstract

The relative contributions of sulfur atoms of dietary L-Cys and L-Met to the syntheses of proteins and GSH in rat liver were examined. 1) When the amount of sulfur-containing amino acids in L-Trp-deficient diets was fixed at 0.36%, incorporation of L-[35S]Cys into GSH was proportional to the amount of L-Cys administered, in the presence of L-Met in the diet. Incorporation of 35S from L-Met into GSH was lower than that from the same amount of L-Cys and became negligible in the presence of a large amount of L-Cys. 2) When rats were given L-Trp-deficient diet, more L-Cys was always incorporated into liver GSH than into proteins. But, when rats were given L-Trp-fortified diet containing more L-Met than L-Cys, more L-Cys was incorporated into liver proteins than into GSH. 3) Met-sulfur was preferentially incorporated into liver proteins with or without L-Trp. Its absolute incorporation into proteins was significantly greater in the presence of L-Trp than in its absence. 4) When the amount of L-Met in the diet was increased from 0.18 to 0.36 or 0.54%, incorporation of Met-sulfur into proteins increased proportionally, in the presence of 0.18% L-Cys. Unexpectedly, incorporation of L-Cys formed from L-Met into liver proteins was larger than that from L-[3H]Met itself. L-Cys formed from L-Met was incorporated into proteins more readily than L-Cys given as such. 5) When the amount of L-Met in the diet was increased from 0.18 to 0.54%, incorporation of Met-35S into GSH increased 8-fold. Even with a large excess of L-Met, L-Cys was invariably incorporated into GSH. 6) These results are consistent with the role of liver GSH as a reservoir of cysteine, as proposed by us.