Role of cysteine in the dietary control of the expression of 3-phosphoglycerate dehydrogenase in rat liver

Shifting rats to a protein-free, carbohydrate-rich diet, although not starv ation, resulted in the appearance of mRNA for, and activity of, 3-phosphogl ycerate dehydrogenase (3-PGDH) in liver as well as in a marked decrease in plasma cystine concentration. Refeeding with protein caused a 50% decrease in the mRNA in sh and its complete disappearance within 24 h, followed by a slower disappearance of the enzymic activity. Intraperitoneal administrati on of cysteine or methionine to protein-starved rats decreased the mRNA by 50-60% after 8 h. However, the repeated administration of cysteine failed t o cause the complete disappearance of this mRNA in 24 h. In hepatocytes in primary culture, cysteine plus methionine and glucagon had, independently, an approx. 4-fold inhibitory effect on the abundance of the 3-PGDH mRNA and caused its almost complete disappearance when tested together. Insulin had an approx. 2-fold stimulatory effect, which was antagonized by cysteine pl us methionine but was still apparent in the presence of glucagon. Nuclear r un-on experiments and analysis of the stability of the mRNA with 5,6-dichlo robenzimidazole riboside, an inhibitor of RNA polymerase II, suggested that the effect: of cysteine plus methionine was due to destabilization of the mRNA, whereas the effect of glucagon was exerted on transcription. Cysteine , but not methionine, inhibited the accumulation of 3-PGDH mRNA in FTO2B he patoma cells. In conclusion, the dietary control of the expression of the 3 -PGDH gene in liver seems to involve the negative effects of cysteine and g lucagon and the positive effect of insulin.