Skip to main content

Galactosamine hepatitis: Key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death

  • Chapter
  • First Online:
Reviews of Physiology, Biochemistry and Pharmacology, Volume 71

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 71))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anukarahanonta, T., Shinozuka, H., Farber, E.: Inhibition of protein synthesis in rat liver by d-galactosamine. Res. Commun. Chem. Pathol. and Pharmacol. 5, 481–491 (1973).

    Google Scholar 

  • Ballard, F. J.: Purification and properties of galactokinase from pig liver. Biochem. J. 98, 347–352 (1966).

    PubMed  Google Scholar 

  • Bates, C. J., Adams, W. R., Handschumacher, R. E.: Control of the formation of uridine diphospho-N-acetylhexosamine and glycoprotein synthesis in rat liver. J. Biol. Chem. 241, 1705–1712 (1966).

    PubMed  Google Scholar 

  • Bauer, Ch., Bachmann, W., Reutter, W.: Studies on galactosamine hepatitis: Determination of galactosamine metabolites in the developing rat liver. Hoppe-Seyler's Z. Physiol. Chem. 353, 1053–1058 (1972).

    PubMed  Google Scholar 

  • Bauer, Ch., Reutter, W.: Inhibition of uridine diphosphoglucose dehydrogenase by galactosamine-1-phosphate and UDP-galactosamine. Biochim. Biophys. Acta 293, 11–14 (1973).

    PubMed  Google Scholar 

  • Bekesi, J. G., Winzler, R. J.: The effect of d-glucosamine on the adenine and uridine nucleotides of sarcoma 180 ascites tumor cells. J. Biol. Chem. 244, 5663–5668 (1969).

    PubMed  Google Scholar 

  • Bertoli, D., Segal, S.: Developmental aspects and some characteristics of mammalian galactose-1-phosphate uridyltransferase. J. Biol. Chem. 241, 4023–4029 (1966).

    PubMed  Google Scholar 

  • Bresnick, E.: Early changes in pyrimidine biosynthesis after partial hepatectomy. J. Biol. Chem. 240, 2550–2556 (1965).

    PubMed  Google Scholar 

  • Burch, H. B., Max, P., Jr., Chyu, K., Lowry, O. H.: Metabolic intermediates in liver of rats given large amounts of fructose or dihydroxyacetone. Biochem. Biophys. Res. Commun. 34, 619–626 (1969).

    Article  PubMed  Google Scholar 

  • Chambon, P.: Personal communication (1972).

    Google Scholar 

  • Colombi, A., Thölen, H., Engelhardt, G., Hecht, Y., Koller, F.: Gerinnungsfaktoren als Parameter des Leberzellschadens bei akuter Hepatitis. In: K. Beck (Ed.), Ikterus, pp. 323–326. Stuttgart: F. K. Schattauer 1968.

    Google Scholar 

  • Creasey, W. A., Handschumacher, R. E.: Purification and properties of orotidylate decarboxylases from yeast and rat liver. J. Biol. Chem. 236, 2058–2063 (1961).

    PubMed  Google Scholar 

  • Cuatrecasas, P., Segal, S.: Mammalian galactokinase, developmental and adaptive characteristics in the rat liver. J. Biol. Chem. 240, 2382–2388 (1965).

    PubMed  Google Scholar 

  • Decker, K., Keppler, D.: Galactosamine-induced liver injury. In: H. Popper and F. Schaffner (Eds.), Progress in Liver Diseases, Vol. 4, pp. 183–199. New York: Grune & Stratton 1972.

    Google Scholar 

  • Decker, K., Keppler, D., Pausch, J.: The regulation of pyrimidine nucleotide level and its role in experimental hepatitis. Advances in Enzyme Regulation 11, 205–230 (1973).

    Article  PubMed  Google Scholar 

  • Decker, K., Keppler, D., Rudigier, J., Domschke, W.: Cell damage by trapping of biosynthetic intermediates. The role of uracil nucleotides in experimental hepatitis. Hoppe-Seyler's Z. Physiol. Chem. 352, 412–418 (1971).

    PubMed  Google Scholar 

  • De Ritis, F., Coltorti, M., Giusti, G.: Serum and liver transaminase activities in experimental virus hepatitis in mice. Science 124, 32 (1956).

    Google Scholar 

  • De Wulf, H., Stalmans, W., Hers, H.-G.: The effect of glucose and of a treatment by glucocorticoids on the activation in vitro of liver glycogen synthetase. Eur. J. Biochem. 15, 1–8 (1970).

    Article  PubMed  Google Scholar 

  • Farber, J. L., Gill, G., Konishi, Y.: Prevention of galactosamine-induced liver cell necrosis by uridine. Am. J. Pathol. 72, 53–62 (1973).

    PubMed  Google Scholar 

  • Fischer, W., Weidemann, G.: Nachweis des Leloir-Weges in Pflanzen mit 2-Desoxy-d-galaktose. Biochim. Biophys. Acta 93, 677–680 (1964a).

    Google Scholar 

  • Fischer, W., Weidemann, G.: Die Umsetzung von 2-Desoxy-d-galaktose im Stoffwechsel. II. Identifizierung der phosphorylierten Zwischenprodukte. Hoppe-Seyler's Z. Physiol. Chem. 336, 206–218 (1964b).

    PubMed  Google Scholar 

  • Gerlach, U., Hiby, W.: Sorbit-Dehydrogenase. In: Methoden der enzymatischen Analyse (H. U. Bergmeyer, Ed.), 2nd ed., pp. 527–533. Weinheim: Verlag Chemie 1970.

    Google Scholar 

  • Grün, M., Brunswig, D., Mersch-Baumert, K., Conradt, M., Hörder, M. H., Laun, A., Liehr, H., Krauss, H., Richter, E.: Gerinnungsstörungen bei der „Galaktosamin-Hepatitis“ der Ratte. Acta Hepato-Gastroenterol. 19, 103–108 (1972).

    Google Scholar 

  • Hänninen, D., Marniemi, J.: Inhibition of glucuronide synthesis by physiological metabolites in liver slices. FEBS Letters 6, 177–181 (1970).

    Article  PubMed  Google Scholar 

  • Keppler, D.: Hépatite expérimentale à la d-galactosamine. Ann. Gastroent. Hepatol. 9, 211–221 (1973).

    Google Scholar 

  • Keppler, D., Bischoff, E., Decker, K.: The role of uridine nucleotides in galactosamine hepatitis. 7th Congr. Clin. Chem., Geneva/Evian 1969; Vol.3, pp. 456–460. Basel: Karger 1970c.

    Google Scholar 

  • Keppler, D., Decker, K.: Studies on the mechanism of galactosamine hepatitis: Accumulation of galactosamine-1-phosphate and its inhibition of UDP-glucose pyrophosphorylase. Eur. J. Biochem. 10, 219–225 (1969).

    Article  PubMed  Google Scholar 

  • Keppler, D., Decker, K.: Der Wirkungsmechanismus von d-Galaktosamin in der Leber. Verh. Deutsch. Ges. Inn. Med. 77, 1179–1182 (1971).

    PubMed  Google Scholar 

  • Keppler, D., Decker, K.: UTP depletion induced by sugars: Reversibility and early consequences in liver. Abstr. Commun. Meet. Fed. Europ. Biochem. Soc. 8, 1043 (1972).

    Google Scholar 

  • Keppler, D., Fröhlich, J., Reutter, W., Wieland, O., Decker, K.: Changes in uridine nucleo-tides during liver perfusion with d-galactosamine. FEBS Letters 4, 278–280 (1969).

    Article  PubMed  Google Scholar 

  • Keppler, D., Hübner, G. Liver injury induced by 2-deoxy-d-galactose. Exptl. Mol. Pathol. 19, 365–377 (1973).

    Article  Google Scholar 

  • Keppler, D., Lesch, R., Reutter, W., Decker, K.: Experimental hepatitis induced by d-galactosamine. Exptl. Mol. Pathol. 9, 279–290 (1968).

    Article  Google Scholar 

  • Keppler, D., Pausch, J., Decker, K.: Selective uridine triphosphate deficiency induced by d-galactosamine in liver and reversed by pyrimidine nucleotide precursors. Effect on ribonucleic acid synthesis. J. Biol. Chem. 249, 211–216 (1974).

    PubMed  Google Scholar 

  • Keppler, D., Rudigier, J., Bischoff, E., Decker, K.: The trapping of uridine phosphates by d-galactosamine, d-glucosamine, and 2-deoxy-d-galactose. A study on the mechanism of galactosamine hepatitis. Eur. J. Biochem. 17, 246–253 (1970b).

    Article  PubMed  Google Scholar 

  • Keppler, D., Rudigier, J., Decker, K.: Trapping of uridine phosphates by d-galactose in ethanol-treated liver. FEBS Letters 11, 193–196 (1970d).

    Article  PubMed  Google Scholar 

  • Keppler, D., Rudigier, J., Decker, K.: Enzymic determination of uracil nucleotides in tissues. Anal. Biochem. 38, 105–114 (1970e).

    Article  PubMed  Google Scholar 

  • Keppler, D., Rudigier, J., Reutter, W., Lesch, R., Decker, K.: Orotate prevents galactosamine hepatitis. Hoppe-Seyler's Z. Physiol. Chem. 351, 102–104 (1970a).

    PubMed  Google Scholar 

  • Keppler, D., Smith, D. F.: Nucleotide contents of ascites hepatoma cells and their changes induced by d-galactosamine. Cancer Res. 34, 705–711 (1974).

    PubMed  Google Scholar 

  • Koff, R. S., Gordon, G., Sabesin, S. M.: D-Galactosamine hepatitis. I. Hepatocellular injury and fatty liver following a single dose. Proc. Soc. Exptl. Biol. Med. 137, 696–701 (1971).

    Google Scholar 

  • Kornfeld, S., Kornfeld, R., Neufeld, E. F., O'Brien, P. J.: The feedback control of sugar nucleotide biosynthesis in liver. Proc. Natl. Acad. Sci. U. S. 52, 371–379 (1964).

    Google Scholar 

  • Kuhn, R., Leppelmann, J. H., Fischer, H.: Stoffwechselversuche mit radioaktiv markiertem d-Glucosamin und d-Galaktosamin. Liebigs Ann. Chem. 620, 15–20 (1959).

    Google Scholar 

  • Lesch, R., Bauer, Ch., Reutter, W.: The development of cholangiofibrosis and hepatomas in galactosamine-induced cirrhotic rat livers. Virchow's Arch. Abt. B Zellpath. 12, 285–289 (1973).

    Google Scholar 

  • Lesch, R., Keppler, D., Reutter, W., Rudigier, J., Oehlert, W., Decker, K.: Entwicklung einer experimentellen Leberzirrhose durch d-Galactosamin. Histologische, biochemische und autoradiographische Untersuchungen an Ratten. Virchow's Arch. Abt. B Zellpath. 6, 57–71 (1970a).

    Google Scholar 

  • Lesch, R., Reutter, W., Keppler, D., Decker, K.: Liver restitution after acute galactosamine hepatitis: Autoradiographic and biochemical studies in rats. Exptl. Mol. Pathol. 12, 58–69 (1970b).

    Article  Google Scholar 

  • Levine, R. L., Hoogenraad, N. J., Kretchmer, N.: Regulation of activity of carbamoyl phosphate synthetase from mouse spleen. Biochemistry 10, 3694–3699 (1971).

    Article  PubMed  Google Scholar 

  • Maley, F.: The synthesis of UDP-galactosamine and UDP-N-acetylgalactosamine. Biochem. Biophys. Res. Commun. 39, 371–378 (1970).

    Article  PubMed  Google Scholar 

  • Maley, F., Maley, G. F.: The enzymic conversion of glucosamine to galactosamine. Biochim. Biophys. Acta 31, 577–578 (1959).

    Article  PubMed  Google Scholar 

  • Maley, F., Tarentino, A. L., McGarrahan, J. F., Delgiacco, R.: The metabolism of d-galactosamine and N-acetyl-d-galactosamine in rat liver. Biochem. J. 107, 637–644 (1968).

    Google Scholar 

  • Marinozzi, V., Fiume, L.: Effects of α-amanitin on mouse and rat liver cell nuclei. Exper. Cell Res. 67, 311–312(1971).

    Article  Google Scholar 

  • Marniemi, J., Nurminen, J., Hänninen, O. Studies on the action of d-galactose and d-galactosamine on the glucuronide synthesis in the rat tissues. Int. J. Biochem. 4, 227–233 (1973).

    Article  Google Scholar 

  • Medline, A., Schaffner, F., Popper, H.: Ultrastructural features in galactosamine-induced hepatitis. Exptl. Mol. Pathol. 12, 201–211 (1970).

    Article  Google Scholar 

  • Mersmann, H. J., Segal, H. L.: An on-off mechanism for liver glycogen synthetase activity. Proc. Natl. Acad. Sci. U. S. 58, 1688–1695 (1967).

    Google Scholar 

  • Möhr, J. R., Mattenheimer, H., Holmes, A. W., Deinhardt, F., Schmidt, F. W.: Enzymology of experimental liver disease in Marmoset monkeys. Enzyme 12, 161–179 (1971).

    PubMed  Google Scholar 

  • Monier, D., Wagle, S. R.: Studies on gluconeogenesis in galactosamine-induced hepatitis. Proc. Soc. Exptl. Biol. Med. 136, 377–380 (1971).

    Google Scholar 

  • Müller-Berghaus, G., Reuter, C.: Disseminated intravascular coagulation in galactosamine-induced experimental hepatitis. Thrombosis Res. 1, 473–486 (1972).

    Article  Google Scholar 

  • Pausch, J., Keppler, D., Decker, K.: Activity and distribution of the enzymes of uridylate synthesis from orotate in animal tissues. Biochim. Biophys. Acta 258, 395–403 (1972a).

    PubMed  Google Scholar 

  • Pausch, J., Keppler, D., Decker, K.: Increased activities of hepatic orotidine 5′-phosphate pyrophosphorylase and orotidine 5′-phosphate decarboxylase induced by orotate. FEBS Letters 20, 330–332 (1972b).

    Article  PubMed  Google Scholar 

  • Pausch, J., Keppler, D., Decker, K.: Zur Bedeutung der Aktivität von Enzymen der Pyrimidinbiosynthese für die Entwicklung der Galaktosaminschädigung der Leber. Verh. Deutsch. Ges. Inn. Med. 78, 1375–1378 (1972c).

    PubMed  Google Scholar 

  • Reutter, W., Bachmann, W.: Galaktosaminhepatitis: Schädigung der Plasmamembran der Leberzelle nach Gabe von d-Galaktosamin. Verh. Deutsch. Ges. Inn. Med. 77, 1177–1178 (1971).

    PubMed  Google Scholar 

  • Reutter, W., Bauer, Ch., Bachmann, W., Lesch, R.: Über die primäre und sekundäre biochemische Antwort der Leber nach Gabe von d-Galaktosamin beim Zustandekommen der Galaktosaminhepatitis. Verh. Deutsch. Ges. Inn. Med. 79, 927–930 (1973).

    PubMed  Google Scholar 

  • Reutter, W., Bauer, Ch., Bachmann, W., Lesch, R.: The galactosamine-refractory regenerating rat liver. In: R. Lesch and W. Reutter (Eds.), Liver regeneration after experimental injury. New York: Intercontinental Medical Book Corp., in press.

    Google Scholar 

  • Reutter, W., Bauer, Ch., Lesch, R.: On the mechanism of action of galactosamine: Different response to d-galactosamine of rat liver during development. Die Naturwissenschaften 57, 674–675 (1970).

    Article  Google Scholar 

  • Reutter, W., Keppler, D., Lesch, R., Decker, K.: Zum Glykoproteidstoffwechsel bei der Galaktosamin-induzierten Hepatitis. Verh. Deutsch. Ges. Inn. Med. 75, 363–365 (1969).

    PubMed  Google Scholar 

  • Reynolds, R. D., Reutter, W.: Inhibition of induction of rat liver tyrosine aminotransferase by d-galactosamine. Role of uridine triphosphate. J. Biol. Chem. 248, 1562–1567 (1973).

    PubMed  Google Scholar 

  • Scharnbeck, H., Schaffner, F., Keppler, D., Decker, K.: Ultrastructural studies on the effect of choline orotate on galactosamine induced hepatic injury in rats. Exptl. Mol. Pathol. 16, 33–46 (1972).

    Article  Google Scholar 

  • Schmidt, E.: Glutamat-Dehydrogenase, UV-Test. In: Methoden der enzymatischen Analyse (H. U. Bergmeyer, Ed.), 2nd Ed., pp. 607–613. Weinheim: Verlag Chemie 1970.

    Google Scholar 

  • Scholtissek, C: Detection of an unstable RNA in chick fibroblasts after reduction of the UTP pool by glucosamine. Eur. J. Biochem. 24, 358–365 (1971).

    Article  PubMed  Google Scholar 

  • Scornik, O. A.: Decreased in vivo disappearance of labelled liver protein after partial hepatectomy. Biochem. Biophys. Res. Commun. 47, 1063–1066 (1972).

    Article  PubMed  Google Scholar 

  • Shinozuka, H., Farber, J. L., Konishi, Y., Anukarahanonta, T.: d-Galactosamine and acute liver cell injury. Fed. Proc. 32, 1516–1526 (1973a).

    PubMed  Google Scholar 

  • Shinozuka, H., Martin, J. T., Farber, J. L.: The induction of fibrillar nucleoli in rat liver cells by d-galactosamine and their subsequent re-formation into normal nucleoli. J. Ultrastruct. Res. 44, 279–292 (1973b).

    Article  PubMed  Google Scholar 

  • Siebert, G.: The biochemical environment of the mammalian nucleus. Sub-Cell. Biochem. 1, 277–292 (1972).

    Google Scholar 

  • Smith, P. C., Knott, C. E., Tremblay, G. C.: Detection of the feedback control of pyrimidine biosynthesis in slices of several rat tissues. Biochem. Biophys. Res. Commun. 55, 1141–1146 (1973).

    Article  PubMed  Google Scholar 

  • Stirpe, F., Fiume, L.: Studies on the pathogenesis of liver necrosis by α-amanitin. Effect of α-amanitin on ribonucleic acid synthesis and on ribonucleic acid polymerase in mouse liver nuclei. Biochem. J. 105, 779–782 (1967).

    PubMed  Google Scholar 

  • Thorn, W.: Organstoffwechsel und Organfunktion. In: H. Bartelheimer, W. Heyde, W. Thorn (Eds.), „d-Glucose und verwandte Verbindungen in Medizin und Biologie“, p. 378–425. Stuttgart: Enke Verlag 1966.

    Google Scholar 

  • Walker, D. G., Khan, H. H.: Some properties of galactokinase in developing rat liver. Biochem. J. 108, 169–175 (1968).

    PubMed  Google Scholar 

  • Weber, G., Queener, S. F., Ferdinandus, J. A.: Control of gene expression in carbohydrate, pyrimidine and DNA metabolism. Advances in Enzyme Regulation 9, 63–95 (1971).

    Article  Google Scholar 

  • White, B. N., Shetlar, M. R., Shurley, H. M., Schilling, J. A.: Incorporation of d-[1-14C]-galactosamine into serum proteins and tissues of the rat. Biochim. Biophys. Acta 101, 259–266 (1965).

    PubMed  Google Scholar 

  • Wieland, T., Wieland, O.: Chemistry and toxicology of the toxins of Amanita phalloides. Pharmacol. Rev. 11, 87–107 (1959).

    PubMed  Google Scholar 

  • Wieland, T., Wieland, O.: The toxic peptides of amanita species. In: S. Kadis, A. Ciegler, S. J. Ail (Eds.), Microbial Toxins, Vol. 8, pp. 249–280. New York and London: Academic Press 1972.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 1974 Springer Verlag

About this chapter

Cite this chapter

Decker, K., Keppler, D. (1974). Galactosamine hepatitis: Key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. In: Reviews of Physiology, Biochemistry and Pharmacology, Volume 71. Reviews of Physiology, Biochemistry and Pharmacology, vol 71. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0027661

Download citation

  • DOI: https://doi.org/10.1007/BFb0027661

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-06939-3

  • Online ISBN: 978-3-540-37864-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics