Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1984 Jan 15;217(2):477–483. doi: 10.1042/bj2170477

Distinct effects of glucagon and vasopressin on proline metabolism in isolated hepatocytes. The role of oxoglutarate dehydrogenase.

J M Staddon, J D McGivan
PMCID: PMC1153239  PMID: 6141793

Abstract

The hormonal regulation of gluconeogenesis and ureogenesis in isolated rat hepatocytes with 5 mM-proline as precursor was studied, with the following results. (1) The formation of glucose and urea in a 30 min interval were stimulated more by vasopressin than by glucagon, and the effects of the two hormones in combination were additive. (2) The rates of gluconeogenesis during the 30 min were constant under control, glucagon-stimulated and glucagon-plus-vasopressin-stimulated conditions. The stimulated rate in the presence of vasopressin diminished with time; glucagon in combination with vasopressin prevented this diminution, resulting in an additive effect. (3) Coincident with these changes in gluconeogenesis, vasopressin caused a decrease in cell oxoglutarate concentration, which, in contrast with the decrease caused by glucagon, was greater, but not sustained unless glucagon was also present. Changes in cell glutamate concentration similar to those observed for oxoglutarate occurred. (4) The data suggest that activation of oxoglutarate dehydrogenase (EC 1.2.4.2) by glucagon and vasopressin by different mechanisms may explain the relative effects of the hormones alone and in combination on gluconeogenesis from proline.

Full text

PDF
478

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brosnan J. T., Krebs H. A., Williamson D. H. Effects of ischaemia on metabolite concentrations in rat liver. Biochem J. 1970 Mar;117(1):91–96. doi: 10.1042/bj1170091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brosnan J. T., Williamson D. H. Mechanisms for the formation of alanine and aspartate on rat liver in vivo after administration of ammonium chloride. Biochem J. 1974 Mar;138(3):453–462. doi: 10.1042/bj1380453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brunner G., Neupert W. Localisation of proline oxidase and Delta-pyrroline-5-carboxylic acid dehydrogenase in rat liver. FEBS Lett. 1969 Jun;3(4):283–286. doi: 10.1016/0014-5793(69)80159-6. [DOI] [PubMed] [Google Scholar]
  5. Exton J. H. Molecular mechanisms involved in alpha-adrenergic responses. Mol Cell Endocrinol. 1981 Sep;23(3):233–264. doi: 10.1016/0303-7207(81)90123-4. [DOI] [PubMed] [Google Scholar]
  6. Garrison J. C., Wagner J. D. Glucagon and the Ca2+-linked hormones angiotensin II, norepinephrine, and vasopressin stimulate the phosphorylation of distinct substrates in intact hepatocytes. J Biol Chem. 1982 Nov 10;257(21):13135–13143. [PubMed] [Google Scholar]
  7. Hems D. A., Whitton P. D. Control of hepatic glycogenolysis. Physiol Rev. 1980 Jan;60(1):1–50. doi: 10.1152/physrev.1980.60.1.1. [DOI] [PubMed] [Google Scholar]
  8. Hensgens H. E., Meijer A. J., Williamson J. R., Gimpel J. A., Tager J. M. Prolone metabolism in isolated rat liver cells. Biochem J. 1978 Mar 15;170(3):699–707. doi: 10.1042/bj1700699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hue L., Blackmore P. F., Exton J. H. Fructose 2,6-bisphosphate. Hormonal regulation and mechanism of its formation in liver. J Biol Chem. 1981 Sep 10;256(17):8900–8903. [PubMed] [Google Scholar]
  10. Häussinger D., Gerok W., Sies H. Inhibition of pyruvate dehydrogenase during the metabolism of glutamine and proline in hemoglobin-free perfused rat liver. Eur J Biochem. 1982 Aug;126(1):69–76. doi: 10.1111/j.1432-1033.1982.tb06747.x. [DOI] [PubMed] [Google Scholar]
  11. JOHNSON A. B., STRECKER H. J. The interconversion of glutamic acid and proline. IV. The oxidation of proline by rat liver mitochondria. J Biol Chem. 1962 Jun;237:1876–1882. [PubMed] [Google Scholar]
  12. Joseph S. K., McGivan J. D. The effect of ammonium chloride and glucagon on the metabolism of glutamine in isolated liver cells from starved rats. Biochim Biophys Acta. 1978 Sep 21;543(1):16–28. doi: 10.1016/0304-4165(78)90450-6. [DOI] [PubMed] [Google Scholar]
  13. Joseph S. K., Verhoeven A. J., Meijer A. J. Effect of trifluoperazine on the stimulation by Ca2+-dependent hormones of gluconeogenesis from glutamine in isolated hepatocytes. Biochim Biophys Acta. 1981 Nov 5;677(3-4):506–511. doi: 10.1016/0304-4165(81)90266-x. [DOI] [PubMed] [Google Scholar]
  14. McCormack J. G., Denton R. M. The effects of calcium ions and adenine nucleotides on the activity of pig heart 2-oxoglutarate dehydrogenase complex. Biochem J. 1979 Jun 15;180(3):533–544. doi: 10.1042/bj1800533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Morgan N. G., Blackmore P. F., Exton J. H. Modulation of the alpha 1-adrenergic control of hepatocyte calcium redistribution by increases in cyclic AMP. J Biol Chem. 1983 Apr 25;258(8):5110–5116. [PubMed] [Google Scholar]
  16. Siess E. A., Brocks D. G., Lattke H. K., Wieland O. H. Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. Biochem J. 1977 Aug 15;166(2):225–235. doi: 10.1042/bj1660225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Siess E. A., Brocks D. G., Wieland O. H. Comparative studies on the influence of hormones on metabolite compartmentation in isolated liver cells during gluconeogenesis from lactate. Biochem Soc Trans. 1978;6(6):1139–1144. doi: 10.1042/bst0061139. [DOI] [PubMed] [Google Scholar]
  18. Smith C. M., Bryla J., Williamson J. R. Regulation of mitochondrial alpha-ketoglutarate metabolism by product inhibition at alpha-ketoglutarate dehydrogenase. J Biol Chem. 1974 Mar 10;249(5):1497–1505. [PubMed] [Google Scholar]
  19. Sugden M. C., Ball A. J., Williamson D. H. A second site of vasopressin action on [1-14C]oleate metabolism in isolated rat hepatocytes: increased formation of 14CO2. Biochem Soc Trans. 1980 Oct;8(5):591–592. doi: 10.1042/bst0080591. [DOI] [PubMed] [Google Scholar]
  20. Taylor W. M., Reinhart P. H., Bygrave F. L. Stimulation by alpha-adrenergic agonists of Ca2+ fluxes, mitochondrial oxidation and gluconeogenesis in perfused rat liver. Biochem J. 1983 Jun 15;212(3):555–565. doi: 10.1042/bj2120555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ui M., Exton J. H., Park C. R. Effects of glucagon on glutamate metabolism in the perfused rat liver. J Biol Chem. 1973 Aug 10;248(15):5350–5359. [PubMed] [Google Scholar]
  22. Williamson D. H., Ilic V., Tordoff A. F., Ellington E. V. Interactions between vasopressin and glucagon on ketogenesis and oleate metabolism in isolated hepatocytes from fed rats. Biochem J. 1980 Feb 15;186(2):621–624. doi: 10.1042/bj1860621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Williamson D. H., Lund P., Krebs H. A. The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem J. 1967 May;103(2):514–527. doi: 10.1042/bj1030514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Williamson J. R., Browning E. T., Thurman R. G., Scholz R. Inhibition of glucagon effects in perfused rat liver by (+)decanoylcarnitine. J Biol Chem. 1969 Sep 25;244(18):5055–5064. [PubMed] [Google Scholar]
  25. Williamson J. R., Cooper R. H., Hoek J. B. Role of calcium in the hormonal regulation of liver metabolism. Biochim Biophys Acta. 1981 Dec 30;639(3-4):243–295. doi: 10.1016/0304-4173(81)90012-4. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES