Tissue Glutathione as a Cyst(e)ine Reservoir during Cystine Depletion in Growing Rats

Abstract

Previous data suggest that liver glutathione (GSH) serves as a cyst(e)ine reservoir in rats starved or fed cyst(e)ine-deficient diets. In the present study we investigated whether extrahepatic tissue GSH concentrations also decreased during cystine (Cys-Cys) depletion and whether excess dietary cystine increased tissue GSH and cysteine (Cys) concentrations. Five groups of growing rats (80-100 g) were fed diets containing crystalline L-amino acids differing in methionine (Met) and cystine (Cys-Cys) content for 15 days. All diets were isonitrogenous (1.3 g/100 g diet) and provided the minimum Met (0.17%) required by growing rats. Diet 1 provided 0.17% Met and 0% Cys-Cys, diet 2 (the recommended diet) provided 0.17% Met and 0.26% Cys-Cys, diet 3 provided 0.50% Met and 0% Cys-Cys, diet 4 provided 0.17% Met and 0.39% Cys-Cys and diet 5 provided 0.17% Met and 0.52% Cys-Cys. Diets 2 and 3 were isosulfurous at 3.3 mmol/100 g diet. Diets 4 and 5 provided 50 and 100%, respectively, more Cys-Cys than required when 0.17% Met was present. Animals fed diet 1 (Cys-Cys depletion) had significantly decreased (P less than 0.05) liver, muscle, spleen, heart and thymus GSH concentrations, whereas brain, small intestine and erythrocyte GSH concentrations remained unchanged. Although brain and small intestine Cys concentrations were not affected by Cys-Cys depletion, spleen, heart and liver Cys concentrations decreased significantly (P less than 0.05). Feeding Cys-Cys above the requirement level did not increase GSH and Cys concentrations of any tissue except liver where Cys levels were elevated. The data indicate that liver, muscle, spleen, heart and thymus GSH serve as Cys reservoirs during Cys-Cys depletion.

DL-methionine supplementation of rice-and-bean diets affects gamma-glutamyltranspeptidase activity and glutathione content in livers of growing rats

“…When amino acids containing sulfur are limited in a diet, there is an expected reduction in hepatic GSH levels (5,6,8). However, when sulfur amino acids or methyl donors are supplied, malnourished rats are able to replenish GSH to higher levels than those found in control animals (6,8,9). The present data agree with the cited studies and corroborate the relationship between increases in hepatic GSH concentration and DL-methionine supplementation under conditions of protein deficiency.…”

“…The protein status of the animals, therefore, has an influence on the regulation of GSH levels. In fact, the concentration of hepatic GSH is reduced in cases of protein-energy malnutrition (6)(7)(8), but malnourished rats are able to replenish GSH when sulfur amino acids or methyl donors are provided (6,9).…”

“…U = µmol of p-nitroaniline released/min, at 37 o C; DL-met = DLmethionine. ports (9,10,18) have provided some evidence that liver GSH can function as an endogenous cysteine reservoir during starvation and can provide cysteine for protein synthesis during periods of inadequate cysteine intake (9,18). The breakdown of GSH occurs extracellularly and is catalyzed by GGT (10), which is bound to the external surface of cell membranes (4).…”

Investigation of the effect of silymarin on the liver in experimental sepsis

“…The infectious and inflammatory state, as well as nutritional status, modulate glutathione tissue levels (41,45,46). However, the mechanisms that lead to these metabolic modifications are still poorly understood.…”

Glutamine protects Chinese hamster ovary cells from radiation killing

“…Glutathione is usually present in high levels in the body and, in addition to serving several protective functions, exerts a radioprotective effect by scavenging free radicals in the same manner as cysteine and cysteamine. Glutathione has been considered by some to be a reservoir of cysteine, offering the radioprotective effects of cysteine in a form preferred by the body over the form of cysteine (13,14). Glutamine is converted to glutamic acid and ammonia by the enzyme glutaminase.…”