Skip to main content

Advertisement

Log in

Energy metabolism in brain cells: effects of elevated ammonia concentrations

  • Original Paper
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Both neurons and astrocytes have high rates of glucose utilization and oxidative metabolism. Fully 20% of glucose consumption is used for astrocytic production of glutamate and glutamine, which during intense glutamatergic activity leads to an increase in glutamate content, but at steady state is compensated for by an equally intense oxidation of glutamate. The amounts of ammonia used for glutamine synthesis and liberated during glutamine hydrolysis are large, compared to the additional demand for glutamine synthesis in hyperammonemic animals and patients with hepatic encephalopathy. Nevertheless, elevated ammonia concentrations lead to an increased astrocytic glutamine production and an elevated content of glutamine combined with a decrease in glutamate content, probably mainly in a cytosolic pool needed for normal activity of the malate-asparate shuttle (MAS); another compartment generated by glutamine hydrolysis is increased. As a result of reduced MAS activity the pyruvate/lactate ratio is decreased in astrocytes but not in neurons and decarboxylation of pyruvate to form acetyl coenzyme A is reduced. Elevated ammonia concentrations also inhibit decarboxylation of α-ketoglutarate in the TCA cycle. This effect occurs in both neurons and astrocytes, is unrelated to MAS activity and seen after chronic treatment with ammonia even in the absence of elevated ammonia concentrations.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Ahboucha S, Coyne L, Hirakawa R, Butterworth RF, Halliwell RF (2006) An interaction between benzodiazepines and neuroactive steroids at GABA A receptors in cultured hippocampal neurons. Neurochem Int 48:703–707

    Article  PubMed  CAS  Google Scholar 

  • Aureli T, Di Cocco ME, Calvani M, Conti F (1997) The entry of [1-13C]glucose into biochemical pathways reveals a complex compartmentation and metabolite trafficking between glia and neurons: a study by 13C-NMR spectroscopy. Brain Res 765:218–227

    Article  PubMed  CAS  Google Scholar 

  • Barbiroli B, Gaiani S, Lodi R, Iotti S, Tonon C, Clementi V, Donati G, Bolondi L (2002) Abnormal brain energy metabolism shown by in vivo phosphorus magnetic resonance spectroscopy in patients with chronic liver disease. Brain Res Bull 59:75–82

    Article  PubMed  CAS  Google Scholar 

  • Blüml S, Moreno-Torres A, Ross BD (2001) [1-13C]glucose MRS in chronic hepatic encephalopathy in man. Magn Reson Med 45:981–993

    Article  PubMed  Google Scholar 

  • Blüml S, Moreno-Torres A, Shic F, Nguy CH, Ross BD (2002) Tricarboxylic acid cycle of glia in the in vivo human brain. NMR Biomed 15:1–5

    Article  PubMed  CAS  Google Scholar 

  • Butterworth RF (2002) Pathophysiology of hepatic encephalopathy: a new look at ammonia. Metab Brain Dis 17:221–227

    Article  PubMed  CAS  Google Scholar 

  • Butterworth RF, Giguère JF, Michaud J, Lavoie J, Layrargues GP (1987) Ammonia: key factor in the pathogenesis of hepatic encephalopathy. Neurochem Pathol 6:1–12

    PubMed  CAS  Google Scholar 

  • Chan H, Butterworth RF (2003) Cell-selective effects of ammonia on glutamate transporter and receptor function in the mammalian brain. Neurochem Int 43:525–532

    Article  PubMed  CAS  Google Scholar 

  • Chan H, Zwingmann C, Pannunzio M, Butterworth RF (2003) Effects of ammonia on high affinity glutamate uptake and glutamate transporter EAAT3 expression in cultured rat cerebellar granule cells. Neurochem Int 43:137–146

    Article  PubMed  CAS  Google Scholar 

  • Chatauret N, Zwingmann C, Rose C, Leibfritz D, Butterworth RF (2003) Effects of hypothermia on brain glucose metabolism in acute liver failure: a H/C-nuclear magnetic resonance study. Gastroenterology 125:815–824

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Peng L, Zhang X, Stolzenburg JU, Hertz L (1995) Further evidence that fluoxetine interacts with a 5-HT2C receptor in glial cells. Brain Res Bull 38:153–159

    Article  PubMed  CAS  Google Scholar 

  • Cruz F, Cerdan S (1999) Quantitative 13C NMR studies of metabolic compartmentation in the adult mammalian brain. NMR Biomed 12:451–462

    Article  PubMed  CAS  Google Scholar 

  • Danbolt N (2001) Glutamate uptake. Prog Neurobiol 65:1–105

    Article  PubMed  CAS  Google Scholar 

  • Derouiche A (2004) The perisynaptic astrocyte process as a glial compartment—immunolabeling for glutamine synthetase and other glial markers. In Hertz L (ed.) Non-neuronal cells of the nervous system: function and dysfunction. Elsevier, Amsterdam, pp147–163

  • Desjardins P, Rao KV, Michalak A, Rose C, Butterworth RF (1999) Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle. Metab Brain Dis 14:273–280

    Article  PubMed  CAS  Google Scholar 

  • Dienel GA, Cruz NF (2004) Nutrition during brain activation: does cell-to-cell lactate shuttling contribute significantly to sweet and sour food for thought? Neurochem Int 45:321–351

    Article  PubMed  CAS  Google Scholar 

  • Dienel GA, Hertz L (2005) Astrocytic contributions to bioenergetics of cerebral ischemia. Glia 50:362–388

    Article  PubMed  Google Scholar 

  • Dringen R, Gebhardt R, Hamprecht B (1993) Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Res 623:208–214

    Article  PubMed  CAS  Google Scholar 

  • Faff-Michalak L, Albrecht J (1991) Aspartate aminotransferase, malate dehydrogenase, and pyruvate carboxylase activities in rat cerebral synaptic and nonsynaptic mitochondria: effects of in vitro treatment with ammonia, hyperammonemia and hepatic encephalopathy. Metab Brain Dis 6:187–197

    Article  PubMed  CAS  Google Scholar 

  • Fitzpatrick SM, Cooper AJ, Duffy TE (1983) Use of beta-methylene-d-l-aspartate to assess the role of aspartate aminotransferase in cerebral oxidative metabolism. J Neurochem 41:1370–1383

    Article  PubMed  CAS  Google Scholar 

  • Fitzpatrick SM, Cooper AJL, Hertz L (1988) Effects of ammonia and β-methylene-d-l-aspartate on the oxidation of glucose and pyruvate by neurons and astrocytes in primary cultures. J Neurochem 51:1197–1203

    Google Scholar 

  • Fox PT, Raichle ME (1986) Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci U S A 83:1140–1144

    Article  PubMed  CAS  Google Scholar 

  • Friolet R, Colombo JP, Lazeyras F, Aue WP, Kretschmer R, Zimmermann A, Bachmann C (1989) In vivo 31P NMR spectroscopy of energy rich phosphates in the brain of the hyperammonemic rat. Biochem Biophys Res Commun 159:815–820

    Article  PubMed  CAS  Google Scholar 

  • Gibbs ME, Anderson DG, Hertz L (2006) Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens. Glia 54:214–222

    Google Scholar 

  • Gibbs ME, Lloyd HGE, Santa T, Hertz L (2007) Glycogen is a preferred glutamate precursor during learning in day-old chick: biochemical and behavioral evidence. J Neurosci Res, Epub April 24

  • Gopher A, Lapidot A (1991) Increased cerebral PC activity in hyperammonemic rabbits, 13C NMR isotopomer analysis. 10th Annual Meeting of the Society of Magnetic Resonance in Medicine, San Francisco, CA, p 1050

  • Gruetter R, Seaquist ER, Ugurbil K (2001) A mathematical model of compartmentalized neurotransmitter metabolism in the human brain. Am J Physiol Endocrinol Metab 281:E100–E112

    PubMed  CAS  Google Scholar 

  • Haghighat N, McCandless DW (1997) Effect of ammonium chloride on energy metabolism of astrocytes and C6-glioma cells in vitro. Metab Brain Dis 12:287–298

    Google Scholar 

  • Haghighat N, McCandless DW, Geraminegad P (2000) The effect of ammonium chloride on metabolism of primary neurons and neuroblastoma cells in vitro. Metab Brain Dis 15:151–162

    Article  PubMed  CAS  Google Scholar 

  • Hamprecht B, Verleysdonk S, Wiesinger H (2005) Enzymes of carbohydrate and energy metabolism. In: Kettenmann H and Ransom BR (eds) Neuroglia, 2nd edn., Oxford University Press, Oxford, pp 202–215

    Google Scholar 

  • Hawkins RA, Miller AL, Nielsen RC, Veech RL (1973) The acute action of ammonia on rat brain metabolism in vivo. Biochem J 134:1001–1008

    PubMed  CAS  Google Scholar 

  • Hawkins RA, Jessy J, Mans AM, De Joseph MR (1993) Effect of reducing brain glutamine synthesis on metabolic symptoms of hepatic encephalopathy. J Neurochem 60:1000–1006

    Article  PubMed  CAS  Google Scholar 

  • Hertz L (2004) Intercellular metabolic compartmentation in the brain: past, present and future. Neurochem Int 45:285–296

    Article  PubMed  CAS  Google Scholar 

  • Hertz L, Dienel GA (2002) Energy metabolism in the brain. Int Rev Neurobiol 51:1–102

    PubMed  CAS  Google Scholar 

  • Hertz L, Hertz E (2003) Determination of rate of glutamate-sustained oxygen consumption in primary cultures of astrocytes as a means to estimate cataplerotic TCA cycle flux. Neurochem Int 43:355–361

    Article  PubMed  CAS  Google Scholar 

  • Hertz L, Zielke HR (2004) Astrocytic control of glutamatergic activity: astrocytes as the stars of the show. Trends Neurosci 27:735–743

    Article  PubMed  CAS  Google Scholar 

  • Hertz L, Murthy ChRK, Lai JCK, Fitzpatrick SM, Cooper AJL (1987) Some metabolic effects of ammonia on astrocytes and neurons in primary cultures. Neurochem Pathol 6:97–129

    PubMed  CAS  Google Scholar 

  • Hertz L, O’Dowd BS, Ng KT, Gibbs ME (2003) Reciprocal changes in forebrain contents of glycogen and of glutamate/glutamine during early memory consolidation in the day-old chick. Brain Res 994:226–233

    Article  PubMed  CAS  Google Scholar 

  • Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219–249

    Google Scholar 

  • Hindfelt B, Plum F, Duffy TE (1977) Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts. J Clin Invest 59:386–396

    PubMed  CAS  Google Scholar 

  • Hof PR, Pascale E, Magistretti PJ (1988) K+ at concentrations reached in the extracellular space during neuronal activity promotes a Ca2+-dependent glycogen hydrolysis in mouse cerebral cortex. J Neurosci 8:1922–1928

    PubMed  CAS  Google Scholar 

  • Huang R, Kala G Murthy ChRK, Hertz L (1994) Effects of chronic exposure to ammonia on glutamate and glutamine interconversion and compartmentation in homogenous primary cultures of mouse astrocytes. Neurochem Res 19:257–265

    Article  PubMed  CAS  Google Scholar 

  • Ibrahim MZ (1975) Glycogen and its related enzymes of metabolism in the central nervous system. Adv Anat Embryol Cell Biol 52:3–89

    PubMed  CAS  Google Scholar 

  • James IM, MacDonnell L, Xanalatos C (1974) Effect of ammonium salts on brain metabolism. J Neurol Neurosurg Psychiatry 37:948–953

    Article  PubMed  CAS  Google Scholar 

  • Jayakumar AR, Rama Rao KV, Schousboe A, Norenberg MD (2004) Glutamine-induced free radical production in cultured astrocytes. Glia 46:296–301

    Article  PubMed  Google Scholar 

  • Jessy J, DeJoseph MR, Hawkins RA (1991) Hyperammonaemia depresses glucose consumption throughout the brain. Biochem J 277:693–696

    PubMed  CAS  Google Scholar 

  • Kala G (1991) Cerebrotoxic Effects of Ammonia at the Cellular level. Ph.D. thesis, University of Saskatchewan, Saskatoon, SK, Canada

  • Kala G, Hertz L (2005) Ammonia effects on pyruvate/lactate production in astrocytes—interaction with glutamate. Neurochem Int 47:4–12

    Article  PubMed  CAS  Google Scholar 

  • Kala G, Kumarathasan J, Peng L, Leenen FH, Hertz L (2000) Stimulation of Na,K+-ATPase activity, increase in potassium uptake and enhanced production of ouabain-like compounds in ammonia-treated mouse astrocytes. Neurochem Int 36:203–211

    Article  PubMed  CAS  Google Scholar 

  • Kanamatsu T, Tsukada Y (1999) Effects of ammonia on the anaplerotic pathway and amino acid metabolism in the brain: an ex vivo 13C NMR spectroscopic study of rats after administering [2-13C]glucose with or without ammonium acetate. Brain Res 841:11–19

    Article  PubMed  CAS  Google Scholar 

  • Kanamori K, Ross BD, Chung JC, Kuo EL (1996) Severity of hyperammonemic encephalopathy correlates with brain ammonia level and saturation of glutamine synthetase in vivo. J Neurochem 67:1584–1594

    Article  PubMed  CAS  Google Scholar 

  • Kaufman EE, Driscoll BF (1992) Carbon dioxide fixation in neuronal and astroglial cells in culture. J Neurochem 58:258–262

    Article  PubMed  CAS  Google Scholar 

  • Keiding S, Sørensen M, Bende D, Munk OL, Ott P, Vilstrup H (2006) Brain metabolism of 13N-ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography. Hepatology 43:42–50

    Article  PubMed  CAS  Google Scholar 

  • Kong EK, Peng L, Chen Y, Yu ACH, Hertz L (2002) Up-regulation of 5-HT2B receptor density and receptor-mediated glycogenolysis in mouse astrocytes by long-term fluoxetine administration. Neurochem Res 27:113–120

    Article  PubMed  CAS  Google Scholar 

  • Kramer L, Tribl B, Gendo A, Zauner C, Schneider B, Ferenci P, Madl C (2000) Partial pressure of ammonia versus ammonia in hepatic encephalopathy. Hepatology 31:30–34

    Article  PubMed  CAS  Google Scholar 

  • Kvamme E, Svenneby G, Hertz L, Schousboe A (1982) Properties of phosphate activated glutaminase in astrocytes cultured from mouse brain. Neurochem Res 7:761–770

    Article  PubMed  CAS  Google Scholar 

  • Kurz GM, Wiesinger H, Hamprecht B (1993) Purification of cytosolic malic enzyme from bovine brain, generation of monoclonal antibodies and immunocytochemical localization of the enzyme in glial cells of neural primary cultures. J Neurochem 60:1467–1474

    Article  PubMed  CAS  Google Scholar 

  • Lai JCK, Cooper AJL (1986) Brain alpha-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors. J Neurochem 47:1376–1386

    Article  PubMed  CAS  Google Scholar 

  • Lai JCK, Murthy ChRK, Cooper AJL, Hertz E, Hertz L (1989) Differential effects of ammonia and beta-methylene-DL-aspartate on metabolism of glutamate and related amino acids by astrocytes and neurons in primary culture. Neurochem Res 14:377–389

    Article  PubMed  CAS  Google Scholar 

  • Lapidot A, Gopher A (1997) Quantitation of metabolic compartmentation in hyperammonemic brain by natural abundance 13C-NMR detection of 13C-15N coupling patterns and isotopic shifts. Eur J Biochem 243:597–604

    Article  PubMed  CAS  Google Scholar 

  • Lebon V, Petersen KF, Cline GW, Shen J, Mason GF, Dufour S, Behar KL, Shulman GI, Rothman DL (2002) Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci 22:1523–1531

    PubMed  CAS  Google Scholar 

  • Lockwood AH (2002) Positron emission tomography in the study of hepatic encephalopathy. Metab Brain Dis 17:431–435

    Article  PubMed  CAS  Google Scholar 

  • Lockwood AH (2004) Blood ammonia levels and hepatic encephalopathy. Metab Brain Dis 19:345–349

    Article  PubMed  CAS  Google Scholar 

  • Lockwood AH, McDonald JM, Reiman RE, Gelbard AS, Laughlin JS, Duffy TE, Plum F (1979) The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest 63:449–460

    Article  PubMed  CAS  Google Scholar 

  • Lockwood AH, Ginsberg MD, Rhoades HM, Gutierrez MT (1986) Cerebral glucose metabolism after portacaval shunting in the rat. Patterns of metabolism and implications for the pathogenesis of hepatic encephalopathy. J Clin Invest 78:86–95

    PubMed  CAS  Google Scholar 

  • Lockwood AH, Yap EWH, Rhoades HM, Wong WH (1991) Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy. J Cereb Blood Flow Metab 11:331–336

    PubMed  CAS  Google Scholar 

  • McKenna MC, Tildon JT, Stevenson JH, Huang X, Kingwell KG (1995) Regulation of mitochondrial and cytosolic malic enzymes from cultured rat brain astrocytes. Neurochem Res 20:1491–1501

    Article  PubMed  CAS  Google Scholar 

  • McKenna MC, Sonnewald U, Huang X, Stevenson J, Zielke HR (1996) Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J Neurochem 66:339–386

    Google Scholar 

  • Muir D, Berl S, Clarke DD (1986) Acetate and fluoroacetate as possible markers for glial metabolism in vivo. Brain Res 380:336–340

    Article  PubMed  CAS  Google Scholar 

  • Muntz JA, Hurwitz J (1951) Effect of potassium and ammonium ions upon glycolysis catalyzed by an extract of rat brain. Arch Biochem 32:124–136

    Article  PubMed  CAS  Google Scholar 

  • Murthy ChRK, Hertz L (1988) Pyruvate decarboxylation in astrocytes and in neurons in primary cultures in the presence and absence of ammonia. Neurochem Res 13:57–61

    Article  PubMed  CAS  Google Scholar 

  • Norenberg MD (1981) The astrocyte in liver disease. In: Fedoroff S, Hertz L (eds) Advances in Cellular Neurobiology, Vol 2. Academic Press, New York, pp 303–352

    Google Scholar 

  • Norenberg MD (1998) Astroglial dysfunction in hepatic encephalopathy. Metab Brain Dis 13:319–335

    Article  PubMed  CAS  Google Scholar 

  • Norenberg MD, Martinez-Hernandez A (1977) Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res 161:303–310

    Article  Google Scholar 

  • Norenberg MD, Huo Z, Neary JT, Roig-Cantesano A (1997) The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: relation to energy metabolism and glutamatergic neurotransmission. Glia 21:124–133

    Article  PubMed  CAS  Google Scholar 

  • Nyberg SL, Cerra FB, Gruetter R (1998) Brain lactate by magnetic resonance spectroscopy during fulminant hepatic failure in the dog. Liver Transpl Surg 4:158–165

    Article  PubMed  CAS  Google Scholar 

  • Ong JP, Aggarwal A, Krieger D, Easley KA, Karafa MT, Van Lente F, Arroliga AC, Mullen KD (2003) Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 114:188–193

    Article  PubMed  CAS  Google Scholar 

  • Ottersen OP, Zhang N, Walberg F (1992) Metabolic compartmentation of glutamate and glutamine: morphological evidence obtained by quantitative immunocytochemistry in rat cerebellum. Neuroscience 46:519–534

    Article  PubMed  CAS  Google Scholar 

  • Öz G, Berkich DA, Henry PG, Xu Y, LaNoue K, Hutson SM, Gruetter R (2004) Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity. J Neurosci 24:11273–11279

    Article  PubMed  CAS  Google Scholar 

  • Peng L, Schousboe A, Hertz L (1991) Utilization of alpha-ketoglutarate as a precursor for transmitter glutamate in cultured cerebellar granule cells. Neurochem Res 16:29–34

    Article  PubMed  CAS  Google Scholar 

  • Peters A, Palay SL, Webster HdeF (1991) The fine structure of the nervous system. Neurons and their supporting cells, 3rd edn. Oxford University Press, Oxford

  • Pichili VB, Rao KV, Jayakumar AR, Norenberg MD (2007) Inhibition of glutamine transport into mitochondria protects astrocytes from ammonia toxicity. Glia 55:801–809

    Google Scholar 

  • Qu H, Eloqayli H, Unsgård G, Sonnewald U (2001) Glutamate decreases pyruvate carboxylase activity and spares glucose as energy substrate in cultured cerebellar astrocytes. J Neurosci Res 66:1127–1132

    Article  PubMed  CAS  Google Scholar 

  • Rama Rao KV, Jayakumar AR, Norenberg MD (2003) Induction of the mitochondrial permeability transition in cultured astrocytes by glutamine. Neurochem Int 43:517–523

    Article  PubMed  CAS  Google Scholar 

  • Rama Rao KV, Jayakumar AR, Norenberg MD (2005) Differential response of glutamine in cultured neurons and astrocytes. J Neurosci Res 79:193–199

    Article  PubMed  CAS  Google Scholar 

  • Ramos M, del Arco A, Pardo B, Martinez-Serrano A, Martinez-Morales JR, Kobayashi K, Yasuda T, Bogonez E, Bovolenta P, Saheki T, Satrustegui J (2003) Developmental changes in the Ca2+-regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord. Dev Brain Res 143:33–46

    Google Scholar 

  • Rao KVR, Norenberg MD (2001) Cerebral energy metabolism in hepatic encephalopathy and hyperammonemia. Metab Brain Dis 16:67–78

    Article  PubMed  CAS  Google Scholar 

  • Rodrigo R, Felipo V (2006) Brain regional alterations in the modulation of the glutamate–nitric oxide–cGMP pathway in liver cirrhosis. Role of hyperammonemia and cell types involved. Neurochem Int 48:472–477

    PubMed  CAS  Google Scholar 

  • Romero-Gomez M, Jover M, Diaz-Gomez D, de Teran LC, Rodrigo R, Camacho I, Echevarria M, Felipo V, Bautista JD (2006) Phosphate-activated glutaminase activity is enhanced in brain, intestine and kidneys of rats following portacaval anastomosis. World J Gastroenterol 12:2406–2411

    PubMed  CAS  Google Scholar 

  • Shank RP, Bennett GS, Freytag SO, Campbell GL (1985) Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res 329:364–367

    Article  PubMed  CAS  Google Scholar 

  • Shulman RG, Hyder F, Rothman DL (2001) Cerebral energetics and the glycogen shunt: neurochemical basis of functional imaging. Proc Natl Acad Sci U S A 98:6417–6422

    Article  PubMed  CAS  Google Scholar 

  • Sibson NR, Dhankhar A, Mason GF, Rothman DL, Behar KL, Shulman RG (1998) Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci U S A 95:316–321

    Article  PubMed  CAS  Google Scholar 

  • Sibson NR, Mason GF, Shen J, Cline GW, Herskovits AZ, Wall JE, Behar KL, Rothman DL, Shulman RG (2001) In vivo 13C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during [2-13C]glucose infusion. J Neurochem 76:975–989

    Article  PubMed  CAS  Google Scholar 

  • Siess E, Wittmann J, Wieland O (1971) Interconversion and kinetic properties of pyruvate dehydrogenase from brain. Hoppe Seyler Z Physiol Chem 352:447–452

    PubMed  CAS  Google Scholar 

  • Sokoloff L (1986) Cerebral circulation, energy metabolism, and protein synthesis: General characteristics and principles of measurement. In: Phelps M Mazziotta J and Schelbert H (eds.) Positron emission tomography and autoradiography: principles and applications for the brain and heart. Raven Press, New York, pp 1–71

    Google Scholar 

  • Strauss GI, Knudsen GM, Kondrup J, Møller K, Larsen FS (2001) Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure. Gastroenterology 121:1109–1119

    Article  PubMed  CAS  Google Scholar 

  • Subbarao KV, Hertz L (1990) Effects of adrenergic agonists on glycogenolysis in primary cultures of astrocytes. Brain Res 527:346–349

    Article  PubMed  CAS  Google Scholar 

  • Subbarao KV, Stolzenburg J-U, Hertz L (1996) Pharmacological characteristics of potassium-induced glycogenolysis in astrocytes. Neurosci Lett 196:45–48

    Article  Google Scholar 

  • Swanson RA, Morton MM, Sagar SM, Sharp FR (1992) Sensory stimulation induces local cerebral glycogenolysis: demonstration by autoradiography. Neuroscience 51:451–461

    Article  PubMed  CAS  Google Scholar 

  • Taylor-Robinson SD, Sargentoni J, Mallalieu RJ, Bell JD, Bryant DJ, Coutts GA, Morgan MY (1994) Cerebral phosphorus-31 magnetic resonance spectroscopy in patients with chronic hepatic encephalopathy. Hepatology 20:1173–1178

    PubMed  CAS  Google Scholar 

  • Waniewski RA, Martin DL (1998) Preferential utilization of acetate by astrocytes is attributable to transport. J Neurosci 18:5225–5233

    PubMed  CAS  Google Scholar 

  • Weissenborn K, Bokemeyer M, Ahl B, Fischer-Wasels D, Giewekemeyer K, van den Hoff J, Kostler H, Berding G (2004) Functional imaging of the brain in patients with liver cirrhosis. Metab Brain Dis 19:269–280

    Article  PubMed  Google Scholar 

  • Wilson NR, Kang J, Hueske EV, Leung T, Varoqui H, Murnick JG, Erickson JD, Liu G (2005) Presynaptic regulation of quantal size by the vesicular glutamate transporter VGLUT1. J Neurosci 25:6221–6234

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Ola MS, Berkich DA, Gardner TW, Barber AJ, Palmieri F, Hutson SM, LaNoue KF (2007) Energy sources for glutamate neurotransmission in the retina: absence of the aspartate/glutamate carrier produces reliance on glycolysis in glia. J Neurochem 101:120–131

    Google Scholar 

  • Yu ACH, Hertz L (1983) Metabolic sources of energy in astrocytes. In: Hertz L, Kvamme E, McGeer EG, Schousboe A (eds.) Glutamine, glutamate and GABA in the central nervous system. Alan R. Liss, New York, pp 327–342

    Google Scholar 

  • Yu ACH, Schousboe A, Hertz L (1982) Metabolic fate of 14C-labeled glutamate in astrocytes in primary cultures. J Neurochem 39:954–960

    Article  PubMed  CAS  Google Scholar 

  • Yu ACH, Drejer J, Hertz L, Schousboe A (1983) Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. J Neurochem 41:1484–1487

    Article  PubMed  CAS  Google Scholar 

  • Yu ACH, Schousboe A, Hertz L (1984) Influence of pathological concentrations of ammonia on metabolic fate of 14C-labelled glutamate in astrocytes in primary cultures. J Neurochem 42:594–597

    Article  PubMed  CAS  Google Scholar 

  • Zhou BG, Norenberg MD (1999) Ammonia downregulates GLAST mRNA glutamate transporter in rat astrocyte cultures. Neurosci Lett 276:145–148

    Article  PubMed  CAS  Google Scholar 

  • Zwingmann C, Butterworth R (2005) An update on the role of brain glutamine synthesis and its relation to cell-specific energy metabolism in the hyperammonemic brain: further studies using NMR spectroscopy. Neurochem Int 47:19–30

    Article  PubMed  CAS  Google Scholar 

  • Zwingmann C, Brand A, Richter-Landsberg C, Leibfritz D (1998) Multinuclear NMR spectroscopy studies on NH4Cl-induced metabolic alterations and detoxification processes in primary astrocytes and glioma cells. Dev Neurosci 20:417–426

    Article  PubMed  CAS  Google Scholar 

  • Zwingmann C, Chatauret N, Leibfritz D, Butterworth RF (2003) Selective increase of brain lactate synthesis in experimental acute liver failure: results of a [H–C] nuclear magnetic resonance study. Hepatology 37:420–428

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The collaboration in many of the studies on which this review is based with the late professor Ch.R.K. Murthy is gratefully acknowledged and remembered.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leif Hertz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hertz, L., Kala, G. Energy metabolism in brain cells: effects of elevated ammonia concentrations. Metab Brain Dis 22, 199–218 (2007). https://doi.org/10.1007/s11011-007-9068-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-007-9068-z

Keywords

Navigation