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. 1985 Sep 1;230(2):457–463. doi: 10.1042/bj2300457

Alpha-adrenergic stimulation of glutamine metabolism in isolated rat hepatocytes.

A J Verhoeven, J M Estrela, A J Meijer
PMCID: PMC1152637  PMID: 2864923

Abstract

The mechanisms by means of which phenylephrine stimulates glutamine metabolism were studied in isolated rat hepatocytes. In the first 2 min after phenylephrine addition there was a rapid fall in the concentrations of intracellular 2-oxoglutarate and glutamate, presumably owing to activation of 2-oxoglutarate dehydrogenase. This was followed 2-3 min later by activation of glutaminase and by increases in glutamate and 2-oxoglutarate. Activation of glutaminase by phenylephrine was due to direct stimulation of the enzyme rather than to reversal of inhibition by the decrease in 2-oxoglutarate and glutamate. The stimulation of glutaminase by phenylephrine is partly due to an increase in the affinity of the enzyme for ammonia, its essential activator. It is concluded that stimulation of steady-state flux through the pathway from glutamine to glucose and urea can only be achieved by stimulation of glutaminase, the first enzyme in the pathway.

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Selected References

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  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. Corvera S., García-Sáinz J. A. Hormonal stimulation of mitochondrial glutaminase. Effects of vasopressin, angiotensin II, adrenaline and glucagon. Biochem J. 1983 Mar 15;210(3):957–960. doi: 10.1042/bj2100957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Groen A. K., Sips H. J., Vervoorn R. C., Tager J. M. Intracellular compartmentation and control of alanine metabolism in rat liver parenchymal cells. Eur J Biochem. 1982 Feb;122(1):87–93. doi: 10.1111/j.1432-1033.1982.tb05851.x. [DOI] [PubMed] [Google Scholar]
  4. Hensgens H. E., Verhoeven A. J., Meijer A. J. The relationship between intramitochondrial N-acetylglutamate and activity of carbamoyl-phosphate synthetase (ammonia). The effect of glucagon. Eur J Biochem. 1980;107(1):197–205. doi: 10.1111/j.1432-1033.1980.tb04640.x. [DOI] [PubMed] [Google Scholar]
  5. Häussinger D., Sies H. Effect of phenylephrine on glutamate and glutamine metabolism in isolated perfused rat liver. Biochem J. 1984 Aug 1;221(3):651–658. doi: 10.1042/bj2210651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Krebs H. A. Metabolism of amino-acids: The synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues. Biochem J. 1935 Aug;29(8):1951–1969. doi: 10.1042/bj0291951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McGivan J. D., Bradford N. M. Characteristics of the activation of glutaminase by ammonia in sonicated rat liver mitochondria. Biochim Biophys Acta. 1983 Sep 13;759(3):296–302. doi: 10.1016/0304-4165(83)90327-6. [DOI] [PubMed] [Google Scholar]
  10. Ochs R. S. Glutamine metabolism of isolated rat hepatocytes. Evidence for catecholamine activation of alpha-ketoglutarate dehydrogenase. J Biol Chem. 1984 Nov 10;259(21):13004–13010. [PubMed] [Google Scholar]
  11. Ochs R. S., Lardy H. A. Catecholamine stimulation of hepatic gluconeogenesis at the site between pyruvate and phosphoenolpyruvate. J Biol Chem. 1983 Aug 25;258(16):9956–9962. [PubMed] [Google Scholar]
  12. Patel M., McGivan J. D. Partial purification and properties of rat liver glutaminase. Biochem J. 1984 Jun 1;220(2):583–590. doi: 10.1042/bj2200583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Staddon J. M., McGivan J. D. Distinct effects of glucagon and vasopressin on proline metabolism in isolated hepatocytes. The role of oxoglutarate dehydrogenase. Biochem J. 1984 Jan 15;217(2):477–483. doi: 10.1042/bj2170477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sugden M. C., Watts D. I. Stimulation of [1-14C]oleate oxidation to 14CO2 in isolated rat hepatocytes by the catecholamines, vasopressin and angiotensin. A possible mechanism of action. Biochem J. 1983 Apr 15;212(1):85–91. doi: 10.1042/bj2120085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Tischler M. E., Hecht P., Williamson J. R. Determination of mitochondrial/cytosolic metabolite gradients in isolated rat liver cells by cell disruption. Arch Biochem Biophys. 1977 May;181(1):278–293. doi: 10.1016/0003-9861(77)90506-9. [DOI] [PubMed] [Google Scholar]
  17. Van Der Meer R., Tager J. M. A simple method for the perfusion of isolated liver cells. FEBS Lett. 1976 Aug 1;67(1):36–40. doi: 10.1016/0014-5793(76)80865-4. [DOI] [PubMed] [Google Scholar]
  18. Verhoeven A. J., Kamer P., Groen A. K., Tager J. M. Effects of thyroid hormone on mitochondrial oxidative phosphorylation. Biochem J. 1985 Feb 15;226(1):183–192. doi: 10.1042/bj2260183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Verhoeven A. J., van Iwaarden J. F., Joseph S. K., Meijer A. J. Control of rat-liver glutaminase by ammonia and pH. Eur J Biochem. 1983 Jun 1;133(1):241–244. doi: 10.1111/j.1432-1033.1983.tb07454.x. [DOI] [PubMed] [Google Scholar]
  20. Wanders R. J., Meijer A. J., Groen A. K., Tager J. M. Bicarbonate and the pathway of glutamate oxidation in isolated rat-liver mitochondria. Eur J Biochem. 1983 Jun 1;133(1):245–254. doi: 10.1111/j.1432-1033.1983.tb07455.x. [DOI] [PubMed] [Google Scholar]
  21. Westerhoff H. V., Groen A. K., Wanders R. J. Modern theories of metabolic control and their applications (review). Biosci Rep. 1984 Jan;4(1):1–22. doi: 10.1007/BF01120819. [DOI] [PubMed] [Google Scholar]
  22. 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]

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