Regulation by insulin of liver carbamoyl-phosphate synthase II (glutamine-hydrolysing).
Evidence is provided that insulin controls the amount and synthetic rate of liver carbamoyl-phosphate synthase II (EC 6.3.5.5) (synthase II) in rat. In 3- and 6-day starvation, with low plasma insulin, synthase II specific activity decreased to 47 and 30%, respectively, of normal; on re-feeding and with concurrent insulin injections, liver synthase II activity increased to 2.5 and 3 times that of starved rats respectively. Treatment with anti-insulin serum during re-feeding prevented the rise in synthase II activity. In diabetic rats, synthase II activity decreased to 28% of normal and was increased by insulin treatment for 2 and 7 days to 4.8- and 5.6-fold of the activity in diabetic liver; this rise in activity was blocked by actinomycin. Immunotitration demonstrated that alterations in synthase II activity were due to changes in the enzyme amount. In starvation, the relative synthesis rate of synthase II decreased to 44%, with an increase in catabolic rate to 122%; re-feeding returned these to control values. In diabetes the synthase II synthesis rate decreased to 52% and the degradative rate was accelerated to 180%; insulin treatment induced synthesis and returned degradation to the control range. Thus the integrative action of insulin in liver pyrimidine metabolism entails regulation of the amount and turnover of synthase II.
Reardon
M A
MA
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46223.
Weber
G
G
D000818:Animals; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000276:immunology / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D005502:Food; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007330:Insulin Antibodies / Q000502:physiology; D008025:Ligases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011743:Pyrimidines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation / Q000201:enzymology
D007328:Insulin; D007330:Insulin Antibodies; D011743:Pyrimidines; D008025:Ligases; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); C030986:pyrimidine