Regulation of carbamoyl-phosphate synthase II. 1986

G Weber, and M Reardon

Evidence was provided that in rat liver synthase II activity, amount and turnover were regulated primarily by insulin. When rats were starved, synthase II activity and the immunotitratable enzyme amount markedly decreased; refeeding restored enzyme activity and amount to normal range. The changes in activity and amount were paralleled with alterations in the level of circulating insulin in the plasma. When starved rats were treated with anti-insulin serum before and during refeeding, the animals consumed the food, but the rise in synthase II activity was prevented. In diabetic rats, the activity and amount of synthase II in the liver markedly decreased and insulin treatment restored them to normal range. Actinomycin treatment prevented the refeeding and the insulin-induced rise in synthase II activity and amount. Study of the turnover of synthase II showed that in starvation the rate of synthesis decreased and refeeding restored the enzyme synthetic and degradation rates to normal range. In the diabetic rat, synthase II synthetic rate markedly decreased, and the degradation rate increased. Insulin returned the synthetic and catabolic rates to normal livers. In rapidly growing rat hepatoma 3924A, synthase II activity and amount were elevated 9- to 10-fold. Turnover studies showed that the synthetic rate in hepatoma 3924A was approximately 10-fold higher than that of normal liver. The catabolic rates of synthase II were similar in the liver and hepatoma. Thus, the increased activity and amount of synthase II in the hepatoma was due primarily to an increased rate of enzyme biosynthesis. Evidence was presented that in starvation and diabetes and on refeeding and insulin administration there is very little or no change in the enzymic activity, amount and turnover of hepatoma synthase II. The marked contrast between the turnover rate of hepatoma 3924A synthase II activity and that of the normal liver enzyme in starvation and in diabetes is under investigation. This overview of the behavior of activity, amount and turnover of synthase II in liver and hepatoma 3924A provides evidence of the important role of insulin in regulation of liver synthase II and of the apparent lack of responsiveness of the hepatoma enzyme to insulin concentrations. The precise details of the experimental procedures and the enzymic results will be published elsewhere.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007330 Insulin Antibodies Antibodies specific to INSULIN. Antibodies, Insulin
D008025 Ligases A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6. Ligase,Synthetases,Synthetase
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008114 Liver Neoplasms, Experimental Experimentally induced tumors of the LIVER. Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008297 Male Males
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002223 Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) An enzyme that catalyzes the formation of carbamoyl phosphate from ATP, carbon dioxide, and glutamine. This enzyme is important in the de novo biosynthesis of pyrimidines. EC 6.3.5.5. Carbamyl Phosphate Synthase (Glutamine),Carbamoyl-Phosphate Synthase (Glutamine),Carbamoylphosphate Synthetase II,Carbamyl Phosphate Synthase II,Carbamyl-Phosphate Synthase (Glutamine),Synthetase II, Carbamoylphosphate
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D005502 Food Substances taken in by the body to provide nourishment. Foods

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