Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1974 Mar;138(3):453–462. doi: 10.1042/bj1380453

Mechanisms for the formation of alanine and aspartate on rat liver in vivo after administration of ammonium chloride

John T Brosnan 1,*, Dermot H Williamson 1
PMCID: PMC1166231  PMID: 4154744

Abstract

1. The time-course of the changes in the concentrations of hepatic metabolites in response to a non-toxic load of NH4Cl were measured in fed and starved rats. 2. There was a rapid increase (after 2min) in [alanine] and [aspartate] which remained high for 10–15min; the absolute increase in [alanine] was smaller in starved rats. 3. These changes were accompanied by a decrease in [oxoglutarate] and in the [3-hydroxybutyrate]/[acetoacetate] ratio. 4. Prior administration of l-arginine to fed rats resulted in smaller increases in [alanine] and [aspartate] after the ammonia load. This is presumably due to stimulation of the urea cycle. 5. Increased formation of alanine in starved rats occurred after prior administration of dihydroxyacetone to increase the availability of pyruvate. 6. Administration of l-cycloserine, an inhibitor of glutamate–alanine aminotransferase, completely prevented the increase in [alanine] after the ammonia load; in this case the absolute increase in [aspartate] was higher. 7. [Oxoglutarate], [citrate] and [isocitrate] at 25min after the ammonia load were higher than the initial concentrations, but returned to normal by 50min. It is suggested that this `overshoot' may be due to temporary compartmentation of oxoglutarate. 8. The mechanisms and physiological significance of alanine and aspartate formation in these experiments are discussed.

Full text

PDF
455

Selected References

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

  1. BIRNBAUM S. M., GREENSTEIN J. P., GULLINO P., OTEY M. C., WINITZ M. Studies on the metabolism of amino acids and related compounds in vivo. III. Prevention of ammonia toxicity by arginine and related compounds. Arch Biochem Biophys. 1956 Oct;64(2):342–354. doi: 10.1016/0003-9861(56)90278-8. [DOI] [PubMed] [Google Scholar]
  2. Bradford N. M., McGivan J. D. Quantitative characteristics of glutamate transport in rat liver mitochondria. Biochem J. 1973 Aug;134(4):1023–1029. doi: 10.1042/bj1341023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Burch H. B., Lowry O. H., Meinhardt L., Max P., Jr, Chyu K. Effect of fructose, dihydroxyacetone, glycerol, and glucose on metabolites and related compounds in liver and kidney. J Biol Chem. 1970 Apr 25;245(8):2092–2102. [PubMed] [Google Scholar]
  5. Clifford A. J., Prior R. L., Visek W. J. Depletion of reduced pyridine nucleotides in liver and blood with ammonia. Am J Physiol. 1969 Nov;217(5):1269–1272. doi: 10.1152/ajplegacy.1969.217.5.1269. [DOI] [PubMed] [Google Scholar]
  6. DU RUISSEAU J. P., GREENSTEIN J. P., WINITZ M., BIRNBAUM S. M. Studies on the metabolism of amino acids and related compounds in vivo. VI. Free amino acid levels in the tissues of rats protected against ammonia toxicity. Arch Biochem Biophys. 1957 May;68(1):161–171. doi: 10.1016/0003-9861(57)90337-5. [DOI] [PubMed] [Google Scholar]
  7. HOHORST H. J., KREUTZ F. H., BUECHER T. [On the metabolite content and the metabolite concentration in the liver of the rat]. Biochem Z. 1959;332:18–46. [PubMed] [Google Scholar]
  8. HOPPER S., SEGAL H. L. Kinetic studies of rat liver glutamicalanine transaminase. J Biol Chem. 1962 Oct;237:3189–3195. [PubMed] [Google Scholar]
  9. KIRSTEN E., GEREZ C., KIRSTEN R. [An enzymatic microdetermination method for ammonia, specifically for extracts of animal tissues and fluids. Determination of NH4 ions in blood]. Biochem Z. 1963;337:312–319. [PubMed] [Google Scholar]
  10. KREBS H. A. Equilibria in transamination systems. Biochem J. 1953 Apr;54(1):82–86. doi: 10.1042/bj0540082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nordmann R., Petit M. A., Nordmann J. Recherches sur le mécanisme de l'accumulation intra-hépatique d'acides aminés dicarboxyliques au cours de l'intoxication ammoniacale. Biochimie. 1972;54(11):1473–1478. [PubMed] [Google Scholar]
  12. Otto K. Alanin-Transaminase und Gluconeogenese. Hoppe Seylers Z Physiol Chem. 1965;341(1):99–104. [PubMed] [Google Scholar]
  13. Palmieri F., Quagliariello E., Klingenberger M. Kinetics and specificity of the oxoglutarate carrier in rat-liver mitochondria. Eur J Biochem. 1972 Sep 25;29(3):408–416. doi: 10.1111/j.1432-1033.1972.tb02003.x. [DOI] [PubMed] [Google Scholar]
  14. Seubert W., Henning H. V., Schoner W., L'age M. Effects of cortisol on the levels of metabolites and enzymes controlling glucose production from pyruvate. Adv Enzyme Regul. 1968;6:153–187. doi: 10.1016/0065-2571(68)90012-5. [DOI] [PubMed] [Google Scholar]
  15. Stone K. J., Hemming F. W. The stereochemistry of hexahydroprenol, ubiquinone and ergosterol biosynthesis in the mycelium of Aspergillus fumigatus Fresenius. Biochem J. 1967 Jul;104(1):43–56. doi: 10.1042/bj1040043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Veech R. L., Eggleston L. V., Krebs H. A. The redox state of free nicotinamide-adenine dinucleotide phosphate in the cytoplasm of rat liver. Biochem J. 1969 Dec;115(4):609–619. doi: 10.1042/bj1150609a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Williamson D. H., Bates M. W., Krebs H. A. Activity and intracellular distribution of enzymes of ketone-body metabolism in rat liver. Biochem J. 1968 Jul;108(3):353–361. doi: 10.1042/bj1080353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Williamson D. H., Lopes-Vieira O., Walker B. Concentrations of free glucogenic amino acids in livers of rats subjected to various metabolic stresses. Biochem J. 1967 Aug;104(2):497–502. doi: 10.1042/bj1040497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Williamson D. H., Veloso D., Ellington E. V., Krebs H. A. Changes in the concentrations of hepatic metabolites on administration of dihydroxyacetone or glycerol to starved rats and their relationship to the control of ketogenesis. Biochem J. 1969 Sep;114(3):575–584. doi: 10.1042/bj1140575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. de Haan E. J., Tager J. M. Evidence for a permeability barrier for alpha-oxoglutarate in rat-liver mitochondria. Biochim Biophys Acta. 1968 Jan 15;153(1):98–112. doi: 10.1016/0005-2728(68)90150-3. [DOI] [PubMed] [Google Scholar]

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

RESOURCES