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. 1965 Feb;94(2):410–426. doi: 10.1042/bj0940410

Influence of pancreatic hormones on enzymes concerned with urea synthesis in rat liver

Patricia McLean 1, F Novello 1,*
PMCID: PMC1206523  PMID: 14348201

Abstract

1. The activities of enzymes of the urea cycle [carbamoyl phosphate synthetase, ornithine transcarbamoylase, argininosuccinate synthetase, argininosuccinase (these last two comprising the arginine-synthetase system) and arginase] have been measured in control, alloxan-diabetic and glucagon-treated rats. In addition, measurements were made on alloxan-diabetic rats treated with protamine–zinc–insulin. 2. Treatment of rats with glucagon for 3 days results in a marked increase in the activities of three enzymes of the urea cycle (carbamoyl phosphate synthetase, argininosuccinate synthetase and argininosuccinase). The pattern of change in the alloxan-diabetic group is very similar to that of the glucagon-treated group, although the magnitude of the change was much greater. 3. Comparison was made of the actual and potential rate of urea synthesis in normal and diabetic rats. In both groups the potential rate of urea production, as measured by the activity of the rate-limiting enzyme, argininosuccinate synthetase, slightly exceeds the actual rate of synthesis by liver slices in the presence of substrates. The relative activities of the actual and potential rates were similar in the two groups of animals, this ratio being 1:0·70. 4. In the alloxan-diabetic rats treated with protamine–zinc–insulin for 2·5 or 4 days there was a marked increase in liver weight. This was associated with a rise in the total hepatic activity of the urea-cycle enzymes located in the soluble fraction of the cell (the arginine-synthetase system and arginase) after 2·5 days of treatment. After 4 days of treatment the concentration of these enzymes/g. of liver decreased, and the total hepatic content then reverted to the untreated alloxan-diabetic value. 5. No effects of glucagon or of insulin in vitro could be found on the rate of urea production by liver slices. 6. The present results are discussed in relation to how far this pattern of change is typical of conditions resulting in a high urea output, and comparison has been made with other values in the literature.

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Selected References

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  1. Atchley D. W., Loeb R. F., Richards D. W., Benedict E. M., Driscoll M. E. ON DIABETIC ACIDOSIS: A Detailed Study of Electrolyte Balances Following the Withdrawal and Reestablishment of Insulin Therapy. J Clin Invest. 1933 Mar;12(2):297–326. doi: 10.1172/JCI100504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BERSON S. A., YALOW R. S., VOLK B. W. In vivo and in vitro metabolism of insulin-I 131 and glucagon-I 131 in normal and cortisone-treated rabbits. J Lab Clin Med. 1957 Mar;49(3):331–342. [PubMed] [Google Scholar]
  3. BROWN G. W., Jr, COHEN P. P. Comparative biochemistry of urea synthesis. I. Methods for the quantitative assay of urea cycle enzymes in liver. J Biol Chem. 1959 Jul;234(7):1769–1774. [PubMed] [Google Scholar]
  4. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bach S. J., Crook E. M., Williamson S. On arginase and its participation in urea synthesis in the liver. Biochem J. 1944;38(4):325–332. doi: 10.1042/bj0380325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CHAIKOFF I. L., FORKER L. L. The antidiabetic action of insulin on nitrogen metabolism. Endocrinology. 1950 Mar;46(3):319–326. doi: 10.1210/endo-46-3-319. [DOI] [PubMed] [Google Scholar]
  7. COPENHAVER J. H., SHIPLEY E. G., MEYER R. K. Enzymes in the tissues of alloxan-diabetic rats. Arch Biochem Biophys. 1951 Dec;34(2):360–371. doi: 10.1016/0003-9861(51)90014-8. [DOI] [PubMed] [Google Scholar]
  8. COX R. W., HENLEY E. D., NARAHARA H. T., VANARSDEL P. P., Jr, WILLIAMS R. H. Studies on the metabolism of glucagon-I 131 in rats. Endocrinology. 1957 Feb;60(2):277–284. doi: 10.1210/endo-60-2-277. [DOI] [PubMed] [Google Scholar]
  9. DE DUVE C. Glucagon; the hyperglycaemic glycogenolytic factor of the pancreas. Lancet. 1953 Jul 18;265(6777):99–104. doi: 10.1016/s0140-6736(53)90052-x. [DOI] [PubMed] [Google Scholar]
  10. DE DUVE C., HERS H. G. Carbohydrate metabolism. Annu Rev Biochem. 1957;26:149–180. doi: 10.1146/annurev.bi.26.070157.001053. [DOI] [PubMed] [Google Scholar]
  11. FASELLA P., BAGLIONI C., TURANO C., SILIPRANDI N. Pyridoxal phosphate and tryptophan metabolism in alloxan-diabetic rats. Clin Chim Acta. 1960 Jan;5:146–148. doi: 10.1016/0009-8981(60)90102-9. [DOI] [PubMed] [Google Scholar]
  12. FITCH W. M., CHAIKOFF I. L. Directions and patterns of adaptation induced in liver enzymes of the diabetic rat by the feeding of glucose and fructose. Biochim Biophys Acta. 1962 Mar 12;57:588–595. doi: 10.1016/0006-3002(62)91168-x. [DOI] [PubMed] [Google Scholar]
  13. FLORES G., ROSADO A., TORRES J., SOBERON G. Liver enzyme activities in ammonia fixation by the rat. Am J Physiol. 1962 Jul;203:43–48. doi: 10.1152/ajplegacy.1962.203.1.43. [DOI] [PubMed] [Google Scholar]
  14. FREEDLAND R. A., SODIKOFF C. H. Effect of diets and hormones on two urea cycle enzymes. Proc Soc Exp Biol Med. 1962 Feb;109:394–396. doi: 10.3181/00379727-109-27215. [DOI] [PubMed] [Google Scholar]
  15. FROHMAN C. E., ORTEN J. M. Tracer studies of acids of the tricarboxylic acid cycle. II. Effect of fructose and bicarbonate on acetate metabolism in livers of diabetic rats. J Biol Chem. 1956 May;220(1):315–319. [PubMed] [Google Scholar]
  16. Fearon W. R. The carbamido diacetyl reaction: a test for citrulline. Biochem J. 1939 Jun;33(6):902–907. doi: 10.1042/bj0330902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Folley S. J., Greenbaum A. L. Determination of the arginase activities of homogenates of liver and mammary gland: effects of pH and substrate concentration and especially of activation by divalent metal ions. Biochem J. 1948;43(4):537–549. doi: 10.1042/bj0430537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. GERHART J. C., PARDEE A. B. The enzymology of control by feedback inhibition. J Biol Chem. 1962 Mar;237:891–896. [PubMed] [Google Scholar]
  19. GLOCK G. E., MCLEAN P. Effects of hormones on levels of oxidized and reduced diphosphopyridine nucleotide and triphosphopyridine nucleotide in liver and diaphragm. Biochem J. 1955 Nov;61(3):397–402. doi: 10.1042/bj0610397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. GREENBAUM A. L., GRAYMORE C. N. The effect of pituitary growth hormone and of insulin on the level of oxidized and reduced coenzyme I in the livers of normal and diabetic rats. Biochem J. 1956 May;63(1):163–167. doi: 10.1042/bj0630163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gornall A. G., Hunter A. A colorimetric method for the determination of citrulline. Biochem J. 1941 Jun;35(5-6):650–658. doi: 10.1042/bj0350650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. HAFT D. E., MILLER L. L. Alloxan diabetes and demonstrated direct action of insulin on metabolism of isolated perfused rat liver. Am J Physiol. 1958 Jan;192(1):33–42. doi: 10.1152/ajplegacy.1957.192.1.33. [DOI] [PubMed] [Google Scholar]
  23. HELMREICH E., HOLZER H., LAMPRECHT W., GOLDSCHMIDT S. Bestimmung stationärer Zwischenstoffkonzentrationen. II. Die Entstehung der Ketokörper und ihre Beziehung zur Glykolyse. Hoppe Seylers Z Physiol Chem. 1954;297(3-6):113–126. [PubMed] [Google Scholar]
  24. HOHORST H. J., KREUTZ F. H., REIM M., HUEBENER H. J. The oxidation/reduction state of the extramitochondrial DPN/DPNH system in rat liver and the hormonal control of substrate levels in vivo. Biochem Biophys Res Commun. 1961 Mar 10;4:163–168. doi: 10.1016/0006-291x(61)90263-7. [DOI] [PubMed] [Google Scholar]
  25. KIRSTEN E., KIRSTEN R., HOHORST H. J., BUECHER T. Free amino acids in alloxan diabetic rat livers. Biochem Biophys Res Commun. 1961 Mar 10;4:169–174. doi: 10.1016/0006-291x(61)90264-9. [DOI] [PubMed] [Google Scholar]
  26. KLEBANOFF S. J., GREENBAUM A. L. The effect of pH on the diabetogenic action of alloxan. J Endocrinol. 1954 Nov;11(4):314–322. doi: 10.1677/joe.0.0110314. [DOI] [PubMed] [Google Scholar]
  27. KORITZ S. B., COHEN P. P. Colorimetric determination of carbamylamino acids and related compounds. J Biol Chem. 1954 Jul;209(1):145–150. [PubMed] [Google Scholar]
  28. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  29. LUKENS F. D. The pancreas: insulin and glucagon. Annu Rev Physiol. 1959;21:445–474. doi: 10.1146/annurev.ph.21.030159.002305. [DOI] [PubMed] [Google Scholar]
  30. MCLEAN P., GURNEY M. W. Effect of adrenalectomy and of growth hormone on enzymes concerned with urea synthesis in rat liver. Biochem J. 1963 Apr;87:96–104. doi: 10.1042/bj0870096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. MCLEAN P., NOVELLO F., GURNEY M. W. SOME OBSERVATIONS ON THE COLORIMETRIC DETERMINATION OF CITRULLINE AND UREA. Biochem J. 1965 Feb;94:422–426. doi: 10.1042/bj0940422. [DOI] [PubMed] [Google Scholar]
  32. MILLER L. L. Glucagon: a protein catabolic hormone in the isolated perfused rat liver. Nature. 1960 Jan 23;185:248–248. doi: 10.1038/185248a0. [DOI] [PubMed] [Google Scholar]
  33. MILLER L. L. Some direct actions of insulin, glucagon, and hydrocortisone on the isolated perfused rat liver. Recent Prog Horm Res. 1961;17:539–568. [PubMed] [Google Scholar]
  34. RANDLE P. J. Endocrine control of metabolism. Annu Rev Physiol. 1963;25:291–324. doi: 10.1146/annurev.ph.25.030163.001451. [DOI] [PubMed] [Google Scholar]
  35. RATNER S., ANSLOW W. P., Jr, PETRACK B. Biosynthesis of urea. VI. Enzymatic cleavage of argininosuccinic acid to arginine and fumaric acid. J Biol Chem. 1953 Sep;204(1):115–125. [PubMed] [Google Scholar]
  36. ROSEN F., ROBERTS N. R., NICHOL C. A. Glucocorticosteroids and transaminase activity. I. Increased activity of glutamicpyruvic transaminase in four conditions associated with gluconeogenesis. J Biol Chem. 1959 Mar;234(3):476–480. [PubMed] [Google Scholar]
  37. SALTER J. M., DAVIDSON I. W., BEST C. H. The pathologic effects of large amounts of glucagon. Diabetes. 1957 May-Jun;6(3):248-52; discussion, 252-5. doi: 10.2337/diab.6.3.248. [DOI] [PubMed] [Google Scholar]
  38. SALTER J. M., DE MEYER R., BEST C. H. Effect of insulin and glucagon on tumour growth. Br Med J. 1958 Jul 5;2(5087):5–7. doi: 10.1136/bmj.2.5087.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. SCHIMKE R. T. Adaptive characteristics of urea cycle enzymes in the rat. J Biol Chem. 1962 Feb;237:459–468. [PubMed] [Google Scholar]
  40. SCHIMKE R. T. Differential effects of fasting and protein-free diets on levels of urea cycle enzymes in rat liver. J Biol Chem. 1962 Jun;237:1921–1924. [PubMed] [Google Scholar]
  41. SCHIMKE R. T. Studies on factors affecting the levels of urea cycle enzymes in rat liver. J Biol Chem. 1963 Mar;238:1012–1018. [PubMed] [Google Scholar]
  42. TYBERGHEIN J. M. The hyperglycemic action of glucagon as influenced by liver glycogen concentration, the pancreas, the adrenals and the pituitary in the baboon (Papio ursinus). Endocrinology. 1961 Aug;69:312–318. doi: 10.1210/endo-69-2-312. [DOI] [PubMed] [Google Scholar]
  43. TYBERGHEIN J. Action du glucagon sur le métabolisme des protéines. Arch Int Physiol. 1953 Feb;61(1):104–107. doi: 10.3109/13813455309150156. [DOI] [PubMed] [Google Scholar]
  44. UNGER R. H., EISENTRAUT A. M., McCALL M. S., MADISON L. L. Measurements of endogenous glucagon in plasma and the influence of blood glucose concentration upon its secretion. J Clin Invest. 1962 Apr;41:682–689. doi: 10.1172/JCI104525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. WOOL I. G., MUNRO A. J. AN INFLUENCE OF INSULIN ON THE SYNTHESIS OF A RAPIDLY LABELED RNA BY ISOLATED RAT DIAPHRAGM. Proc Natl Acad Sci U S A. 1963 Nov;50:918–923. doi: 10.1073/pnas.50.5.918. [DOI] [PMC free article] [PubMed] [Google Scholar]

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