ARS | Publication request: Synthesis of Erythrocyte Glutathione in Normal Adults Consuming the Safe Level of Dietary Protein.

Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 5, 2004
Publication Date: June 1, 2004
Citation: Jackson, A.A., Gibson, N.R., Lu, Yi, Jahoor, Farook 2004. Synthesis of erythrocyte glutathione in healthy adults consuming the safe amount of dietary protein. The American Journal of Clinical Nutrition. 80(1):101-107.

Interpretive Summary: Jackson AA, Gibson NR, Lu Y, Jahoor F. Synthesis of erythrocyte glutathione in healthy adults consuming the safe amount of dietary protein. Am J Clin Nutr. 2004; 80(1):101-7. Glutathione (GSH) is the most important anti-oxidant and detoxicant in the cell. It is synthesized in large quantities from three amino acids, glutamate, glycine and cysteine and its rate of synthesis falls when dietary protein intake falls. The FAO/WHO recommended safe level of dietary protein intake for healthy adults is 0.75 g/kg/d. However, most Western population's habitual intakes range from 1 to 1.5 g/kg/d. Hence it is not known whether healthy individuals will be able to maintain the synthesis of GSH on the recommended safe level of protein. The primary objective of this study was to determine the effect of the safe protein intake on the synthesis rate of GSH in erythrocytes. Erythrocyte GSH fractional synthesis rate and urinary 5-L-oxoproline excretion were measured in 12 young adults by using an infusion of [13C2]glycine on 3 occasions: initially during the subjects' habitual protein intake of1.13 g/kg/d and on days 3 and 10 of consumption of a diet providing the safe protein intake of 0.75 g/kg/d. Compared with baseline values, the synthesis rate of erythrocyte GSH was significantly lower on days 3 and 10 of the diet with the safe protein intake. Urinary 5-L-oxoproline excretion increased significantly above baseline by the third day of the diet with the safe protein intake and remained elevated. Erythrocyte GSH concentrations and absolute synthesis rates decreased by day 3 but recovered to baseline values by day 10. Erythrocyte concentrations of cysteine, methionine, and serine remained unchanged, whereas erythrocyte concentrations of glycine, glutamic acid, and glutamine increased significantly by day 10. These results suggest that during adaptation to the safe amount of dietary protein, there are changes in the concentration and kinetics of erythrocyte GSH that suggest a reduced antioxidant capacity and possible increased susceptibility to oxidant stress.

Technical Abstract: The finding that plasma glutathione turnover decreases as dietary protein intake decreases suggests that the safe amount of dietary protein, although sufficient for maintenance of nitrogen balance, may be insufficient for maintenance of cellular glutathione. Our objective was to determine the effect of the safe protein intake on the erythrocyte glutathione synthesis rate and its relation with urinary 5-L-oxoproline excretion. Erythrocyte glutathione synthesis and urinary 5-L-oxoproline excretion were measured in young adults (6 men and 6 women) by using an infusion of [(13)C(2)]glycine on 3 occasions: initially during the subjects' habitual protein intake (1.13 g.kg(-1).d(-1)) and on days 3 and 10 of consumption of a diet providing the safe protein intake (0.75 g.kg(-1).d(-1)). Compared with baseline values, the fractional synthesis rate of erythrocyte glutathione was significantly lower (P < 0.05) on days 3 and 10 of the diet with the safe protein intake. Urinary 5-L-oxoproline excretion increased significantly (P < 0.05) above baseline by the third day of the diet with the safe protein intake and remained elevated. Erythrocyte glutathione concentrations and absolute synthesis rates decreased by day 3 but recovered to baseline values by day 10. Erythrocyte concentrations of cysteine, methionine, and serine remained unchanged, whereas erythrocyte concentrations of glycine, glutamic acid, and glutamine increased significantly by day 10. During adaptation to the safe amount of dietary protein, there are changes in the concentration and kinetics of erythrocyte glutathione that suggest a reduced antioxidant capacity and possible increased susceptibility to oxidant stress.