| First Author | Tillman JB | Year | 1996 |
| Journal | J Biol Chem | Volume | 271 |
| Issue | 7 | Pages | 3500-6 |
| PubMed ID | 8631954 | Mgi Jnum | J:31426 |
| Mgi Id | MGI:78934 | Doi | 10.1074/jbc.271.7.3500 |
| Citation | Tillman JB, et al. (1996) Dietary calorie restriction in mice induces carbamyl phosphate synthetase I gene transcription tissue specifically. J Biol Chem 271(7):3500-6 |
| abstractText | Dietary calorie restriction (CR) delays age-related physiologic changes, increases maximum life span, and reduces cancer incidence. Here, we present the novel finding that chronic reduction of dietary calories by 50% without changing the intake of dietary protein induced the activity of mouse hepatic carbamyl phosphate synthetase I (CpsI) 5-fold. In liver, CpsI protein, mRNA, and gene transcription were each stimulated by approximately 3-fold. Thus, CR increased both the rate of gene transcription and the specific activity of the enzyme. Short-term feeding studies demonstrated that higher cpsI expression was due to CR and not consumption of more dietary protein. Intestinal CpsI activity was stimulated 2-fold, while its mRNA level did not change, suggesting enzyme activity or translation efficiency was stimulated. CpsI catalyzes the conversion of metabolic ammonia to carbamyl phosphate, the rate-limiting step in urea biosynthesis. cpsI induction suggests there is a shift in the metabolism of calorie-restricted animals toward protein catabolism. CpsI induction likely facilitates metabolic detoxification of ammonia, a strong neurotoxin. Enhanced protein turnover and metabolic detoxification may extend life span. Physiologic similarities between calorie-restricted and hibernating animals suggest the effects of CR may be part of a spectrum of adaptive responses that include hibernation. |
