Influence of Dietary Levels of Protein and Sulfur Amino Acids on Metabolism of Glutathione and Related Amino Acids in Mice.

Abstract

We investigated the metabolism of glutathione (GSH) and sulfur amino acids in various tissues of C57BL male mice fed on a 24.8% protein diet (normal protein diet, NPD), a 7.5% protein diet (low protein diet, LPD), and an amino acid supplemented diet (ASD), which contained 7.5% protein and the same levels of sulfur amino acids as NPD. Although the hepatic total GSH (TGSH) concentration was lower in LPD-fed mice than in NPD-fed mice, that in ASD-fed mice recovered to the level in NPD-fed mice. TGSH concentrations in the brain and plasma were highest in ASD-fed mice, whereas those in the kidney and blood were similar in the three dietary groups. Concentrations of L-methionine and L-cystathionine, an intermediate in the metabolism from L-methionine to L-cysteine, in the brain, kidney and plasma were highest in ASD-fed mice, whereas hepatic concentrations were similar. Brain uptake of 14C-L-methionine for 60 min was higher in LPD-fed mice than in NPD-fed mice, and was further enhanced in ASD-fed mice. Accordingly, this would account for the highest brain concentrations of sulfur amino acids in ASD-fed mice. Thus, the concentrations of TGSH and sulfur amino acids were markedly higher in various tissues in ASD-fed mice than in not only LPD- but also NPD-fed mice. These results suggest that the metabolism of GSH and sulfur amino acids would drastically change by a supplement of sulfur amino acids with a lowered protein diet, at least partly because of their excessive levels compared with the other amino acids.