Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1988 Oct 1;255(1):139–144. doi: 10.1042/bj2550139

The effect of ketone bodies on alanine and glutamine metabolism in isolated skeletal muscle from the fasted chick.

G Y Wu 1, J R Thompson 1
PMCID: PMC1135201  PMID: 2904261

Abstract

The effects of ketone bodies on the metabolism of alanine and glutamine were studied in isolated extensor digitorum communis (EDC) muscles from 24 h-fasted chicks. (1) Acetoacetate and DL-beta-hydroxybutyrate (4 mM) markedly inhibit branched-chain amino acid (BCAA) transamination and alanine formation. (2) Ketone bodies (1 and 4 mM) increase the intracellular concentration and release of glutamate and glutamine, suggesting that inhibition of BCAA transamination does not limit intracellular availability of glutamate for alanine synthesis. (3) Ketone bodies (1 and 4 mM) do not affect glucose uptake by muscles, but decrease the rate of glycolysis as well as the intracellular concentration and release of pyruvate in muscles. (4) Addition of 12 mM-glucose increases the formation of alanine in muscles incubated in the absence of ketone bodies, but has no effect in muscles incubated in the presence of 4 mM ketone bodies. (5) Addition of 5 mM-pyruvate to the media prevents the inhibiting effect of ketone bodies on BCAA transamination and alanine synthesis. These results suggest that ketone bodies decrease alanine synthesis by limiting the intracellular availability of pyruvate, owing to inhibition of glycolysis, and inhibit BCAA transamination by decreasing the intracellular concentration of amino-group acceptors such as pyruvate in EDC muscles from fasted chicks.

Full text

PDF

Selected References

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

  1. BUSCH H., HURLBERT R. B., POTTER V. R. Anion exchange chromatography of acids of the citric acid cycle. J Biol Chem. 1952 May;196(2):717–727. [PubMed] [Google Scholar]
  2. Buse M. G., Biggers J. F., Friderici K. H., Buse J. F. Oxidation of branched chain amino acids by isolated hearts and diaphragms of the rat. The effect of fatty acids, glucose, and pyruvate respiration. J Biol Chem. 1972 Dec 25;247(24):8085–8096. [PubMed] [Google Scholar]
  3. Caldecourt M. A., Cox D. J., Sugden M. C., Palmer T. N. Glycolytic origin of alanine formed in rat diaphragm muscle in vitro. Biochem J. 1985 Nov 1;231(3):801–804. doi: 10.1042/bj2310801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cersosimo E., Williams P. E., Radosevich P. M., Hoxworth B. T., Lacy W. W., Abumrad N. N. Role of glutamine in adaptations in nitrogen metabolism during fasting. Am J Physiol. 1986 Jun;250(6 Pt 1):E622–E628. doi: 10.1152/ajpendo.1986.250.6.E622. [DOI] [PubMed] [Google Scholar]
  5. Cersosimo E., Williams P., Hoxworth B., Lacy W., Abumrad N. Glutamine blocks lipolysis and ketogenesis of fasting. Am J Physiol. 1986 Mar;250(3 Pt 1):E248–E252. doi: 10.1152/ajpendo.1986.250.3.E248. [DOI] [PubMed] [Google Scholar]
  6. Chang T. W., Goldberg A. L. The metabolic fates of amino acids and the formation of glutamine in skeletal muscle. J Biol Chem. 1978 May 25;253(10):3685–3693. [PubMed] [Google Scholar]
  7. Chang T. W., Goldberg A. L. The origin of alanine produced in skeletal muscle. J Biol Chem. 1978 May 25;253(10):3677–3684. [PubMed] [Google Scholar]
  8. Clausen T., Flatman J. A. Effects of insulin and epinephrine on Na+-K+ and glucose transport in soleus muscle. Am J Physiol. 1987 Apr;252(4 Pt 1):E492–E499. doi: 10.1152/ajpendo.1987.252.4.E492. [DOI] [PubMed] [Google Scholar]
  9. Felig P. Amino acid metabolism in man. Annu Rev Biochem. 1975;44:933–955. doi: 10.1146/annurev.bi.44.070175.004441. [DOI] [PubMed] [Google Scholar]
  10. Garber A. J., Karl I. E., Kipnis D. M. Alanine and glutamine synthesis and release from skeletal muscle. I. Glycolysis and amino acid release. J Biol Chem. 1976 Feb 10;251(3):826–835. [PubMed] [Google Scholar]
  11. Goldstein L. Ammonia production and excretion in the mammalian kidney. Int Rev Physiol. 1976;11:283–316. [PubMed] [Google Scholar]
  12. Goldstein L., Newsholme E. A. The formation of alanine from amino acids in diaphragm muscle of the rat. Biochem J. 1976 Feb 15;154(2):555–558. doi: 10.1042/bj1540555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldstein L., Perlman D. F., McLaughlin P. M., King P. A., Cha C. J. Muscle glutamine production in diabetic ketoacidotic rats. Biochem J. 1983 Sep 15;214(3):757–767. doi: 10.1042/bj2140757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jones B. N., Gilligan J. P. o-Phthaldialdehyde precolumn derivatization and reversed-phase high-performance liquid chromatography of polypeptide hydrolysates and physiological fluids. J Chromatogr. 1983 Aug 26;266:471–482. doi: 10.1016/s0021-9673(01)90918-5. [DOI] [PubMed] [Google Scholar]
  15. King P. A., Goldstein L., Newsholme E. A. Glutamine synthetase activity of muscle in acidosis. Biochem J. 1983 Nov 15;216(2):523–525. doi: 10.1042/bj2160523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kohn P. G., Clausen T. The relationship between the transport of glucose and cations across cell membranes in isolated tissues. VI. The effect of insulin, ouabain, and metabolic inhibitors on the transport of 3-O-methylglucose and glucose in rat soleus muscles. Biochim Biophys Acta. 1971 Feb 2;225(2):277–290. doi: 10.1016/0005-2736(71)90221-5. [DOI] [PubMed] [Google Scholar]
  17. LaNoue K., Nicklas W. J., Williamson J. R. Control of citric acid cycle activity in rat heart mitochondria. J Biol Chem. 1970 Jan 10;245(1):102–111. [PubMed] [Google Scholar]
  18. Lee S. H., Davis E. J. Carboxylation and decarboxylation reactions. Anaplerotic flux and removal of citrate cycle intermediates in skeletal muscle. J Biol Chem. 1979 Jan 25;254(2):420–430. [PubMed] [Google Scholar]
  19. Maruyama K., Sunde M. L., Harper A. E. Conditions affecting plasma amino acid patterns in chickens fed practical and purified diets. Poult Sci. 1976 Sep;55(5):1615–1626. doi: 10.3382/ps.0551615. [DOI] [PubMed] [Google Scholar]
  20. Olsen C. An enzymatic fluorimetric micromethod for the determination of acetoacetate, -hydroxybutyrate, pyruvate and lactate. Clin Chim Acta. 1971 Jul;33(2):293–300. doi: 10.1016/0009-8981(71)90486-4. [DOI] [PubMed] [Google Scholar]
  21. Ozand P. T., Tildon J. T., Wapnir R. A., Cornblath M. Alanine formation by rat muscle homogenate. Biochem Biophys Res Commun. 1973 Jul 2;53(1):251–257. doi: 10.1016/0006-291x(73)91427-7. [DOI] [PubMed] [Google Scholar]
  22. Palaiologos G., Felig P. Effects of ketone bodies on amino acid metabolism in isolated rat diaphragm. Biochem J. 1976 Mar 15;154(3):709–716. doi: 10.1042/bj1540709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Palmer T. N., Caldecourt M. A., Snell K., Sugden M. C. Alanine and inter-organ relationships in branched-chain amino and 2-oxo acid metabolism. Review. Biosci Rep. 1985 Dec;5(12):1015–1033. doi: 10.1007/BF01119623. [DOI] [PubMed] [Google Scholar]
  24. Palmer T. N., Caldecourt M. A., Warner J. P., Sugden M. C. Modulation of branched-chain amino acid oxidation in rat hemidiaphragms in vitro by glucose and ketone bodies. Biochem Int. 1985 Sep;11(3):407–413. [PubMed] [Google Scholar]
  25. Ploug T., Galbo H., Vinten J., Jørgensen M., Richter E. A. Kinetics of glucose transport in rat muscle: effects of insulin and contractions. Am J Physiol. 1987 Jul;253(1 Pt 1):E12–E20. doi: 10.1152/ajpendo.1987.253.1.E12. [DOI] [PubMed] [Google Scholar]
  26. Pérez-Sala D., Parrilla R., Ayuso M. S. Key role of L-alanine in the control of hepatic protein synthesis. Biochem J. 1987 Jan 15;241(2):491–498. doi: 10.1042/bj2410491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Robinson A. M., Williamson D. H. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol Rev. 1980 Jan;60(1):143–187. doi: 10.1152/physrev.1980.60.1.143. [DOI] [PubMed] [Google Scholar]
  28. Ruderman N. B., Berger M. The formation of glutamine and alanine in skeletal muscle. J Biol Chem. 1974 Sep 10;249(17):5500–5506. [PubMed] [Google Scholar]
  29. Sherwin R. S., Hendler R. G., Felig P. Effect of ketone infusions on amino acid and nitrogen metabolism in man. J Clin Invest. 1975 Jun;55(6):1382–1390. doi: 10.1172/JCI108057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith R. J., Larson S., Stred S. E., Durschlag R. P. Regulation of glutamine synthetase and glutaminase activities in cultured skeletal muscle cells. J Cell Physiol. 1984 Aug;120(2):197–203. doi: 10.1002/jcp.1041200213. [DOI] [PubMed] [Google Scholar]
  31. Snell K., Duff D. A. Branched-chain amino acid metabolism and alanine formation in rat muscles in vitro. Mitochondrial-cytosolic interrelationships. Biochem J. 1985 Feb 1;225(3):737–743. doi: 10.1042/bj2250737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Snell K. Muscle alanine synthesis and hepatic gluconeogenesis. Biochem Soc Trans. 1980 Apr;8(2):205–213. doi: 10.1042/bst0080205. [DOI] [PubMed] [Google Scholar]
  33. Tinker D. A., Brosnan J. T., Herzberg G. R. Interorgan metabolism of amino acids, glucose, lactate, glycerol and uric acid in the domestic fowl (Gallus domesticus). Biochem J. 1986 Dec 15;240(3):829–836. doi: 10.1042/bj2400829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Umpleby A. M., Chubb D., Boroujerdi M. A., Sonksen P. H. The effect of ketone bodies on leucine and alanine metabolism in dogs. Clin Sci (Lond) 1988 Jan;74(1):41–48. doi: 10.1042/cs0740041. [DOI] [PubMed] [Google Scholar]
  35. Wu G., Thompson J. R. Effect of pyruvate, octanoate and glucose on leucine degradation in skeletal muscle from fed and fasted chicks. Int J Biochem. 1988;20(5):521–526. doi: 10.1016/0020-711x(88)90500-9. [DOI] [PubMed] [Google Scholar]
  36. Wu G., Thompson J. R. Ketone bodies inhibit leucine degradation in chick skeletal muscle. Int J Biochem. 1987;19(10):937–943. doi: 10.1016/0020-711x(87)90175-3. [DOI] [PubMed] [Google Scholar]

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

RESOURCES