Advertisement

Journal of Neural Transmission

, 116:131 | Cite as

Metabolism of galactose in the brain and liver of rats and its conversion into glutamate and other amino acids

  • Martin Roser
  • Djuro Josic
  • Maria Kontou
  • Kurt Mosetter
  • Peter Maurer
  • Werner Reutter
Basic Neurosciences, Genetics and Immunology - Original Article

Abstract

Time- and dose-dependent measurements of metabolites of galactose (with glucose as control) in various organs of rats are discussed. Not only the liver but especially the brain and to a lesser extent the muscles also have the capacity to take up and metabolize galactose. Primarily, the concentrations of UDP-galactose, a pivotal compound in the metabolism of galactose, and UDP-glucose are measured. An important feature lies in the demonstration that galactose and glucose are metabolized to amino acids and that the only increases observed in the brain appear in the concentrations of glutamate, glutamine, GABA measured after acute galactose loads. In addition the increase in the amino acid concentrations after galactose has been administered persists for longer periods of time than after glucose administration. This conversion of hexoses, especially galactose, to amino acids requires the consumption of ammonia equivalents in the brain; this finding might stimulate the use of galactose as a new means of removal of this neurotoxic compound from the brain in patients suffering from hepatic encephalopathy or Alzheimer’s disease.

Keywords

Galactose UDP-galactose UDP-glucose Glutamic acid Brain Liver 

Notes

Acknowledgments

The study has been supported by the Stiftung zur Förderung der Erforschung von Zivilisationskrankheiten Baden-Baden (Germany) and the Sonnenfeld-Stiftung Berlin (Germany).

References

  1. Ashwell G, Harford J (1982) Carbohydrate-specific receptors of the liver. Annu Rev Biochem 51:531–554PubMedCrossRefGoogle Scholar
  2. Bauer CH, Hassels BF, Reutter WG (1976) Galactose metabolism in regenerating rat liver. Biochem J 154:141–147PubMedGoogle Scholar
  3. Berl S, Clarke DD (1983) The metabolic compartmentation concept. In: Hertz L, Kvamme E, McGeer EG, Schousboe A (eds) Glutamine, glutamate and GABA in the central nervous system. Alan R Liss, Inc., New York, pp 205–217Google Scholar
  4. Bertoli D, Segal S (1966) Developmental aspects and some characteristics of mammalian galactose-1-phosphate uridyltransferase. J Biol Chem 241:4023–4029PubMedGoogle Scholar
  5. Blum-Degen D, Frölich L, Hoyer S, Riederer P (1995) Altered regulation of brain glucose metabolism as a cause of neurodegenerative disorders? J Neural Transm Suppl 46:139–147PubMedGoogle Scholar
  6. Brown AM, Ransom BR (2007) Astrocyte glycogen and brain energy metabolism. Glia 55:1263–1271PubMedCrossRefGoogle Scholar
  7. Cohn RM, Segal S (1973) Galactose metabolism and its regulation. Metabolism 22:627–642PubMedCrossRefGoogle Scholar
  8. Cuatrecasas P, Segal S (1965) Mammalian galactokinase: developmental and adaptive characteristics in the rat liver. J Biol Chem 240:2382–2388PubMedGoogle Scholar
  9. Fried R, Beckmann N, Keller U et al (1996) Early glycogenolysis and late glycogenesis in human liver after intravenous administration of galactose. Am J Physiol G14–G19Google Scholar
  10. Garfinkel DA (1966) Simulation study of the metabolism and compartmentation in brain of glutamate, aspartate, the Krebs cycle, and related metabolites. J Biol Chem 241:3918–3929PubMedGoogle Scholar
  11. Geyer A, Gege C, Schmidt RR (2000) Calcium-dependent carbohydrate-carbohydrate recognition between LewisX blood group antigens. Angew Chem Int Ed Engl 39:3246–3249Google Scholar
  12. Gibson JB, Berry GT, Palmieri MJ et al (1996) Sugar nucleotide concentrations in red blood cells of patients on protein- and lactose-limited diets: effect of galactose supplementation. Am J Clin Nutr 63:704–708PubMedGoogle Scholar
  13. Hakomori S, Kobata A (1974) Blood group antigens. In: Sela M (ed) The antigens, vol 2. Academic, New York, pp 79–104Google Scholar
  14. Hamilton PB (1963) Ion exchange chromatography of amino acids. A. Single column, high resolving, fully automatic procedure. Anal Chem 35:2055–2064CrossRefGoogle Scholar
  15. Hellerstein MK, Munro HN (1988) Glycoconjugates as noninvasive probes of intrahepatic metabolism: III. Application to galactose assimilation by the intact rat. Metabolism 37:312–317PubMedCrossRefGoogle Scholar
  16. Hellweg R, Nitsch R, Hock C et al (1992) Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism. J Neurosci Res 479–486Google Scholar
  17. Heuckenkamp PU, Zöllner N (1975) Quantitative comparison and evaluation of utilization of parenteral administered carbohydrates. Nutr Metab 18(Suppl 1):209–226PubMedCrossRefGoogle Scholar
  18. Hoyer S (2004) Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol 490:115–125PubMedCrossRefGoogle Scholar
  19. Hoyer S, Lannert H (2007) Long-term abnormalities in brain glucose/energy metabolism after inhibition of the neuronal insulin receptor: implication of tau-protein. J Neural Transm Suppl 72:195–202PubMedCrossRefGoogle Scholar
  20. Hoyer S, Oesterreich K, Wagner O (1988) Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type? J Neurol 235:143–148PubMedCrossRefGoogle Scholar
  21. Isselbacher KJ, Anderson EP, Kalckar HM (1956) Congenital galactosemia, a single enzymatic block in galactose metabolism. Science 123:635–636PubMedCrossRefGoogle Scholar
  22. Josic D, Hafermaas R, Ch Bauer, Reutter W (1984) Automatic amino acid and sugar analysis of glycoproteins. J Chromatogr A 317:35–39CrossRefGoogle Scholar
  23. Kalckar HM, de Robichon-Szulmajster H (1959) Some aspects of the metabolism of galactose in microorganisms and in man. Bull Soc Chim Biol (Paris) 41:1309–1328Google Scholar
  24. Kalckar HM, Braganca B, Munch-Petersen A (1953) Uridyltransferases and the formation of uridine diphosphogalactose. Nature 172:1039CrossRefGoogle Scholar
  25. Leloir LF (1951) The enzymatic transformation of uridine diphosphate glucose into a galactose derivative. Arch Biochem Biophys 33:186–194CrossRefGoogle Scholar
  26. Lewin LA, Wei R (1966) Microassay of thiamine and its phosphate esters after separation by paper chromatography. Anal Biochem 16:29–35PubMedCrossRefGoogle Scholar
  27. Liu Y, Liu F, Iqbal K et al (2008) Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease. FEBS Lett 582:359–364PubMedCrossRefGoogle Scholar
  28. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  29. Keppler D, Rudigier J, Decker K (1970) Enzymatic determination of uracil nucleotides in tissues. Anal Biochem 38:105–114PubMedCrossRefGoogle Scholar
  30. Kosterlitz HW (1937) CCLXXII. The presence of a galactose-phosphate in the livers of rabbits assimilating galactose. Biochem J 31:2217–2224PubMedGoogle Scholar
  31. Kunst C, Kliegman R, Trindale C (1989) The glucose–galactose paradox in neonatal murine hepatic glycogen synthesis. Am J Physiol 257:E697–E703PubMedGoogle Scholar
  32. Lucka L, Fernando M, Grunow D et al (2005) Identification of Lewis X structures in the cell adhesion molecule CEACAM 1 from human granulocytes. Glycobiology 15:87–100PubMedCrossRefGoogle Scholar
  33. McKenna MC, Gruetter R, Sonnewald U (2006) Energy metabolism of the brain. In: Siegel JG, Albers RW, Brady ST, Price DL et al (eds) Basic neurochemistry. Molecular, cellular, and medical aspects. Academic, Amsterdam, pp 531–557Google Scholar
  34. Meister A (1979) Biochemistry of glutamate: glutamine and glutathione. In: Filer LJ, Garattini S, Kare MR, Reynolds WA, Wurtman RJ (eds) Glutamic acid: advances in biochemistry. Raven Press, New York, pp 69–84Google Scholar
  35. Mueckler M (1994) Facilitate glucose transporters. Eur J Biochem 219:713–725PubMedCrossRefGoogle Scholar
  36. Neufeld EF, Feingold DS, Hassid WZ (1960) Phosphorylation of d-galactose and l-arabinose by extracts from Phaseolus aureus. J Biol Chem 235:906–909PubMedGoogle Scholar
  37. Nordin JH, Hanson RG (1963) Isolation and charaterization of galactose from hydrolysates of glycogen. J Biol Chem 238:489–494PubMedGoogle Scholar
  38. Olson AL, Pessin JE (1996) Structure, function, and regulation of the mammalian facilitate glucose transporter gene family. Annu Rev Nutr 16:235–256PubMedCrossRefGoogle Scholar
  39. Patschinsky T, Leveringhaus M, Werchau H, Reutter W (1980) Conversion of 14C-galactose into amino acids in tissue culture cells and its inhibition by manganese. Eur J Cell Biol 21:63–66PubMedGoogle Scholar
  40. Pellerin L, Magistretti PJ (2003) How to balance the brain energy budget while spending glucose differently. J Physiol 564(2):325–327CrossRefGoogle Scholar
  41. Tauber R, Reutter W (1983) Intramolecular heterogeneity of degradation in plasma membrane glycoproteins: evidence for a general characteristic. Proc Natl Acad Sci USA 4026–4029Google Scholar
  42. Thoden JB, Holden HM (2002) High resolution x-ray structure of galactose mutarotase from Lactococcus lactis. J Biol Chem 277:20854–20861PubMedCrossRefGoogle Scholar
  43. Schlamowitz M (1951) On the nature of rabbit liver glycogen. J Biol Chem 188:145–153PubMedGoogle Scholar
  44. Seiler N (2002) Ammonia and Alzheimer’s disease. Neurochem Int 41:189–207PubMedCrossRefGoogle Scholar
  45. Varki A (1983) Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3:97–130CrossRefGoogle Scholar
  46. Wallenfels K, Hucho F, Herrmann K (1965) Enzymatically catalyzed mutarotation of aldoses. Studies on aldose-1-epimerase from E. coli. Biochem Z 343:307–325PubMedGoogle Scholar
  47. Weijers HA, Kamer JH, van de Dicke WK, Ijsseling J (1961) Diarrhea caused by deficiency of sugar splitting enzymes. I Acta Paediat (Uppsala) 50:55–71CrossRefGoogle Scholar
  48. Wollenberger A, Ristau O, Schoffa G (1960) A simple technique for extremely rapid freezing of large pieces of tissue. Arch Ges Physiol 270:399–407CrossRefGoogle Scholar
  49. Zachara NE, Hart GW (2004) O-GlcNAc a sensor of cellular state: the role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress. Biochim Biophys Acta 1673:13–28PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Martin Roser
    • 1
  • Djuro Josic
    • 3
  • Maria Kontou
    • 2
  • Kurt Mosetter
    • 4
  • Peter Maurer
    • 5
  • Werner Reutter
    • 2
  1. 1.Klinik für Psychiatrie und PsychotherapieNurtingenGermany
  2. 2.Institut für Biochemie und MolekularbiologieCharité-Universitätsmedizin Berlin (Freie Universität Berlin)Berlin-DahlemGermany
  3. 3.Proteomics Core, COBRE Center for Cancer Research DevelopmentRhode Island HospitalProvidenceUSA
  4. 4.Zentrum für interdisziplinäre TherapienKonstanzGermany
  5. 5.Max Grundig KlinikBühlGermany

Personalised recommendations