Skip to main content
SpringerLink
Log in
Book cover

Handbook of Neurochemistry and Molecular Neurobiology pp 1–21Cite as

1 Glutamine, Glutamate, and GABA: Metabolic Aspects

  • Reference work entry
  • First Online:

Abstract:

Glutamine synthesized exclusively in astrocytes is the quantitatively most significant precursor for the excitatory and inhibitory neurotransmitters, glutamate and GABA (γ-aminobutyrate), respectively. Glutamate subsequent to its release and receptor interaction is taken up by surrounding cellular elements, predominantly astrocytes. In astrocytes, glutamate is directly converted to glutamine or it enters the tricarboxylic acid (TCA) cycle. Glutamine is transferred to glutamatergic neurons to serve as precursor for glutamate or for TCA cycle intermediates. The latter is important due to the lack of anaplerosis in neurons. GABA is also taken up by surrounding cellular elements following receptor interaction. However, neuronal reuptake seems to be most important in case of GABA. GABA is either reutilized as neurotransmitter or metabolized via the GABA shunt. To the extent that GABA is lost to the astrocytic compartment, glutamine serves as the precursor for its de novo synthesis. This occurs by deamidation to glutamate and further decarboxylation to GABA. This chapter describes the neuronal and astrocytic enzymatic machineries active in sustaining GABA and glutamate homeostasis involving glutamine and ammonia. The transporters that are also important participants in this scenario are briefly mentioned and for a more detailed description the reader is referred to other chapters.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   299.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

AAT:

aspartate aminotransferase

ALAT:

alanine aminotransferase

BCAT:

branched-chain aminotransferase

GABA:

γ-aminobutyrate

GABA-T:

GABA aminotransferase

GAD:

l-glutamate decarboxylase

GDH:

glutamate dehydrogenase

GS:

glutamine synthetase

PAG:

phosphate-activated glutaminase

PC:

pyruvate carboxylase

PLP:

pyridoxal phosphate

TCA:

tricarboxylic acid

References

  • Alves PM, Nunes R, Zhang C, Maycock CD, Sonnewald U, et al. 2000. Metabolism of 3-13C-malate in primary cultures of mouse astrocytes. Dev Neurosci 22: 456–462.

    Article  CAS  PubMed  Google Scholar 

  • Aoki C, Milner TA, Berger SB, Sheu KF, Blass JP, et al. 1987. Glial glutamate dehydrogenase: Ultrastructural localization and regional distribution in relation to the mitochondrial enzyme, cytochrome oxidase. J Neurosci Res 18: 305–318.

    Article  CAS  PubMed  Google Scholar 

  • Bak LK, Sickmann HM, Schousboe A, Waagepetersen HS. 2005. Activity of the lactate–alanine shuttle is independent of glutamate–glutamine cycle activity in cerebellar neuronal–astrocytic cultures. J Neurosci Res 79: 88–96.

    Article  CAS  PubMed  Google Scholar 

  • Bakken IJ, White LR, Aasly J, Unsgard G, Sonnewald U. 1997. Lactate formation from [U-13C]aspartate in cultured astrocytes: Compartmentation of pyruvate metabolism. Neurosci Lett 237: 117–120.

    Article  CAS  PubMed  Google Scholar 

  • Bakken IJ, White LR, Unsgard G, Aasly J, Sonnewald U. 1998. [U-13C]glutamate metabolism in astrocytes during hypoglycemia and hypoxia. J Neurosci Res 51: 636–645.

    Article  CAS  PubMed  Google Scholar 

  • Balazs R, Machiyama Y, Hammond BJ, Julian T, Richter D. 1970. The operation of the γ-aminobutyrate bypath of the tricarboxylic acid cycle in brain tissue in vitro. Biochem J 116: 445–461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bao J, Cheung WY, Wu JY. 1995. Brain l-glutamate decarboxylase. Inhibition by phosphorylation and activation by dephosphorylation. J Biol Chem 270: 6464–6467.

    CAS  PubMed  Google Scholar 

  • Battaglioli G, Martin DL. 1990. Stimulation of synaptosomal γ-aminobutyric acid synthesis by glutamate and glutamine. J Neurochem 54: 1179–1187.

    Article  CAS  PubMed  Google Scholar 

  • Battaglioli G, Martin DL. 1991. GABA synthesis in brain slices is dependent on glutamine produced in astrocytes. Neurochem Res 16: 151–156.

    Article  CAS  PubMed  Google Scholar 

  • Battaglioli G, Liu H, Martin DL. 2003. Kinetic differences between the isoforms of glutamate decarboxylase: Implications for the regulation of GABA synthesis. J Neurochem 86: 879–887.

    Article  CAS  PubMed  Google Scholar 

  • Baxter CF, Roberts E. 1958. The γ-aminobutyric acid-α-ketoglutaric acid transaminase of beef brain. J Biol Chem 233: 1135–1139.

    Article  CAS  PubMed  Google Scholar 

  • Belhage B, Hansen GH, Elster L, Schousboe A. 1998. Effects of γ-aminobutyric acid (GABA) on synaptogenesis and synaptic function. Perspect Dev Neurobiol 5: 235–246.

    CAS  PubMed  Google Scholar 

  • Belhage B, Hansen GH, Meier E, Schousboe A. 1990. Effects of inhibitors of protein synthesis and intracellular transport on the γ-aminobutyric acid agonist-induced functional differentiation of cultured cerebellar granule cells. J Neurochem 55: 1107–1113.

    Article  CAS  PubMed  Google Scholar 

  • Berl S, Clarke DD. 1969. Compartmentation of amino acid metabolism. Handbook of Neurochemistry, Vol. 2.Lajtha A, editor. New York: Plenum Press, pp. 447–472.

    Chapter  Google Scholar 

  • Berl S, Clarke DD. 1983. The metabolic compartmentation concept. Glutamine, Glutamate and GABA in The Central Nervous System. Hertz L, Kvamme E, McGeer EG, Schousboe A, editors. New York: Alan R. Liss, Inc., pp. 205–217.

    Google Scholar 

  • Berl S, Lajtha A, Waeelsch H. 1961. Amino acid and protein metabolism—IV. Cerebral compartments of glutamic acid metabolism. J Neurochem 7: 186–197.

    CAS  Google Scholar 

  • Berl S, Takagaki G, Clarke DD, Waelsch H. 1962. Metabolic compartments in vivo. Ammonia and glutamic acid metabolism in brain and liver. J Biol Chem 237: 2562–2569.

    CAS  PubMed  Google Scholar 

  • Borden LA. 1996. GABA transporter heterogeneity: Pharmacology and cellular localization. Neurochem Int 29: 335–356.

    Article  CAS  PubMed  Google Scholar 

  • Bradford HF, Ward HK, Thomas AJ. 1978. Glutamine—a major substrate for nerve endings. J Neurochem 30: 1453–1459.

    Article  CAS  PubMed  Google Scholar 

  • Broer S, Brookes N. 2001. Transfer of glutamine between astrocytes and neurons. J Neurochem 77: 705–719.

    Article  CAS  PubMed  Google Scholar 

  • Bu DF, Erlander MG, Hitz BC, Tillakaratne NJ, Kaufman DL, et al. 1992. Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci USA 89: 2115–2119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cerdan S, Kunnecke B, Seelig J. 1990. Cerebral metabolism of [1,2–13C2]acetate as detected by in vivo and in vitro 13C NMR. J Biol Chem 265: 12916–12926.

    Article  CAS  PubMed  Google Scholar 

  • Cesar M, Hamprecht B. 1995. Immunocytochemical examination of neural rat and mouse primary cultures using monoclonal antibodies raised against pyruvate carboxylase. J Neurochem 64: 2312–2318.

    Article  CAS  PubMed  Google Scholar 

  • Chan-Palay V, Wu JY, Palay SL. 1979. Immunocytochemical localization of γ-aminobutyric acid transaminase at cellular and ultrastructural levels. Proc Natl Acad Sci USA 76: 2067–2071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaudhry FA, Reimer RJ, Edwards RH. 2002. The glutamine commute: Take the N line and transfer to the A. J Cell Biol 157: 349–355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chee PY, Dahl JL, Fahien LA. 1979. The purification and properties of rat brain glutamate dehydrogenase. J Neurochem 33: 53–60.

    Article  CAS  PubMed  Google Scholar 

  • Cho SW, Lee J, Choi SY. 1995. Two soluble forms of glutamate dehydrogenase isoproteins from bovine brain. Eur J Biochem 233: 340–346.

    Article  CAS  PubMed  Google Scholar 

  • Choi IY, Lei H, Gruetter R. 2002. Effect of deep pentobarbital anesthesia on neurotransmitter metabolism in vivo: On the correlation of total glucose consumption with glutamatergic action. J Cereb Blood Flow Metab 22: 1343–1351.

    Article  CAS  PubMed  Google Scholar 

  • Christgau S, Aanstoot HJ, Schierbeck H, Begley K, Tullin S, et al. 1992. Membrane anchoring of the autoantigen GAD65 to microvesicles in pancreatic β-cells by palmitoylation in the NH2-terminal domain. J Cell Biol 118: 309–320.

    Article  CAS  PubMed  Google Scholar 

  • Christgau S, Schierbeck H, Aanstoot HJ, Aagaard L, Begley K, et al. 1991. Pancreatic β cells express two autoantigenic forms of glutamic acid decarboxylase, a 65-kDa hydrophilic form and a 64-kDa amphiphilic form which can be both membrane-bound and soluble. J Biol Chem 266: 21257–21264.

    Article  CAS  PubMed  Google Scholar 

  • Colon AD, Plaitakis A, Perakis A, Berl S, Clarke DD. 1986. Purification and characterization of a soluble and a particulate glutamate dehydrogenase from rat brain. J Neurochem 46: 1811–1819.

    Article  CAS  PubMed  Google Scholar 

  • Cooper AJ. 1988. l-Glutamate(2-oxoglutarate) aminotransferases. Glutamine and glutamate in mammals, Vol. 2.Kvamme E, editor. Florida: CRC Press, pp 123–152.

    Google Scholar 

  • Cooper AJ, Lai JC. 1987. Cerebral ammonia metabolism in normal and hyperammonemic rats. Neurochem Pathol 6: 67–95.

    Article  CAS  PubMed  Google Scholar 

  • Cooper AJ, Plum F. 1987. Biochemistry and physiology of brain ammonia. Physiol Rev 67: 440–519.

    Article  CAS  PubMed  Google Scholar 

  • Cooper AJ, McDonald JM, Gelbard AS, Gledhill RF, Duffy TE. 1979. The metabolic fate of 13N-labeled ammonia in rat brain. J Biol Chem 254: 4982–4992.

    Article  CAS  PubMed  Google Scholar 

  • Curtis DR, Watkins JC. 1960. The excitation and depression of spinal neurones by structurally related amino acids. J Neurochem 6: 117–141.

    Article  CAS  PubMed  Google Scholar 

  • Danbolt NC. 2001. Glutamate uptake. Prog Neurobiol 65: 1–105.

    Article  CAS  PubMed  Google Scholar 

  • de Graaf RA, Patel AB, Rothman DL, Behar KL. 2006. Acute regulation of steady-state GABA levels following GABA-transaminase inhibition in rat cerebral cortex. Neurochem Int 48: 508–514.

    Article  CAS  PubMed  Google Scholar 

  • Drejer J, Larsson OM, Kvamme E, Svenneby G, Hertz L, et al. 1985. Ontogenetic development of glutamate metabolizing enzymes in cultured cerebellar granule cells and in cerebellum in vivo. Neurochem Res 10: 49–62.

    Article  CAS  PubMed  Google Scholar 

  • Dringen R, Pfeiffer B, Hamprecht B. 1999. Synthesis of the antioxidant glutathione in neurons: Supply by astrocytes of CysGly as precursor for neuronal glutathione. J Neurosci 19: 562–569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duffy TE, Plum F, Cooper AJL. 1983. Cerebral ammonia metabolism in vivo. Glutamine, Glutamate and GABA in The Central Nervous System. Hertz L, Kvamme E, McGeer EG, Schousboe A. editors. New York: Alan R. Liss, Inc., pp 371–388

    Google Scholar 

  • Erecinska M, Silver IA. 1990. Metabolism and role of glutamate in mammalian brain. Prog Neurobiol 35: 245–296.

    Article  CAS  PubMed  Google Scholar 

  • Erecinska M, Pleasure D, Nelson D, Nissim I, Yudkoff M. 1993. Cerebral aspartate utilization: Near-equilibrium relationships in aspartate aminotransferase reaction. J Neurochem 60: 1696–1706.

    Article  CAS  PubMed  Google Scholar 

  • Erlander MG, Tillakaratne NJ, Feldblum S, Patel N, Tobin AJ. 1991. Two genes encode distinct glutamate decarboxylases. Neuron 7: 91–100.

    Article  CAS  PubMed  Google Scholar 

  • Farinelli SE, Nicklas WJ. 1992. Glutamate metabolism in rat cortical astrocyte cultures. J Neurochem 58: 1905–1915.

    Article  CAS  PubMed  Google Scholar 

  • Filla A, De MG, Brescia M, Palma V, Di LA, Di GG, Campanella G, 1986. Glutamate dehydrogenase in human brain: Regional distribution and properties. J Neurochem 46: 422–424.

    Article  CAS  PubMed  Google Scholar 

  • Fleischer-Lambropoulos E, Kazazoglou T, Geladopoulos T, Kentroti S, Stefanis C, et al. 1996. Stimulation of glutamine synthetase activity by excitatory amino acids in astrocyte cultures derived from aged mouse cerebral hemispheres may be associated with non-N-methyl-d-aspartate receptor activation. Int J Dev Neurosci 14: 523–530.

    Article  CAS  PubMed  Google Scholar 

  • Fonnum F. 1968. The distribution of glutamate decarboxylase and aspartate transaminase in subcellular fractions of rat and guinea-pig brain. Biochem J 106: 401–412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fremeau RT Jr, Troyer MD, Pahner I, Nygaard GO, Tran CH, et al. 2001. The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron 31: 247–260.

    Article  CAS  PubMed  Google Scholar 

  • Gaitonde MK, 1965. Rate of utilization of glucose and compartmentation of α-oxoglutarate and glutamate in rat brain. Biochem J 95: 803–810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gamberino WC, Berkich DA, Lynch CJ, Xu B, LaNoue KF. 1997. Role of pyruvate carboxylase in facilitation of synthesis of glutamate and glutamine in cultured astrocytes. J Neurochem 69: 2312–2325.

    Article  CAS  PubMed  Google Scholar 

  • Garfinkel D. 1966. A simulation study of the metabolism and compartmentation in brain of glutamate, aspartate, the Krebs cycle, and related metabolites. J Biol Biochem 17: 3918–3929.

    Google Scholar 

  • Gegelashvili G, Schousboe A. 1997. High affinity glutamate transporters: Regulation of expression and activity. Mol Pharmacol 52: 6–15.

    Article  CAS  PubMed  Google Scholar 

  • Gegelashvili G, Schousboe A. 1998. Cellular distribution and kinetic properties of high-affinity glutamate transporters. Brain Res Bull 45: 233–238.

    Article  CAS  PubMed  Google Scholar 

  • Gladkevich A, Korf J, Hakobyan VP, Melkonyan KV. 2006. The peripheral GABAergic system as a target in endocrine disorders. Auton Neurosci 124: 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Gram L, Larsson OM, Johnsen AH, Schousboe A. 1988. Effects of valproate, vigabatrin and aminooxyacetic acid on release of endogenous and exogenous GABA from cultured neurons. Epilepsy Res 2: 87–95.

    Article  CAS  PubMed  Google Scholar 

  • Gruetter R, Seaquist ER, Kim S, Ugurbil K. 1998. Localized in vivo 13C-NMR of glutamate metabolism in the human brain: Initial results at 4 Tesla. Dev Neurosci 20: 380–388.

    Article  CAS  PubMed  Google Scholar 

  • Gundersen V, Chaudhry FA, Bjaalie JG, Fonnum F, Ottersen OP, et al. 1998. Synaptic vesicular localization and exocytosis of l-aspartate in excitatory nerve terminals: A quantitative immunogold analysis in rat hippocampus. J Neurosci 18: 6059–6070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hack N, Balazs R. 1994. Selective stimulation of excitatory amino acid receptor subtypes and the survival of granule cells in culture: Effect of quisqualate and AMPA. Neurochem Int 25: 235–241.

    Article  CAS  PubMed  Google Scholar 

  • Hansson E, Rönnbäck L. 2004. Astrocytic receptors and second messenger systems. Advances in Molecular and Cell Biology. Hertz L, editor. The Netherlands: Elsevier, Amsterdam, pp. 475–501.

    Google Scholar 

  • Hassel B, Bråthe A. 2000. Neuronal pyruvate carboxylation supports formation of transmitter glutamate. J Neurosci 20: 1342–1347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hassel B, Johannessen CU, Sonnewald U, Fonnum F. 1998. Quantification of the GABA shunt and the importance of the GABA shunt versus the 2-oxoglutarate dehydrogenase pathway in GABAergic neurons. J Neurochem 71: 1511–1518.

    Article  CAS  PubMed  Google Scholar 

  • Hertz L, Schousboe A. 1975. Ion and energy metabolism of the brain at the cellular level. Int Rev Neurobiol 18: 141–211.

    Article  CAS  PubMed  Google Scholar 

  • Hertz L, Schousboe A. 1987. Primary cultures of GABAergic and glutamatergic neurons as model systems to study neurotransmitter functions. I. Differentiated cells. Model systems of development and aging of the nervous system. Vernadakis A, Privat A, Lauder JM, Timiras PS, Giacobini E, editors. Boston: Martinus Nijhoff publishing, pp 19–31.

    Chapter  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. Epub.

    Google Scholar 

  • Hertz L, Peng L, Westergaard N, Yudkoff M, Schousboe A. 1992. Neuronal–astrocytic interactions in metabolism of transmitter amino acids of the glutamate family. Drug Research Related to Neuroactive Amino Acids, Alfred Benzon Symposium 32. Schousboe A, Diemer NH, Kofod H, editors. Copenhagen: Munksgaard, pp. 30–48.

    Google Scholar 

  • Hsu CC, Thomas C, Chen W, Davis KM, Foos T, et al. 1999. Role of synaptic vesicle proton gradient and protein phosphorylation on ATP-mediated activation of membrane-associated brain glutamate decarboxylase. J Biol Chem 274: 24366–24371.

    Article  CAS  PubMed  Google Scholar 

  • Hutson S. 2001. Structure and function of branched chain aminotransferases. Prog Nucleic Acid Res Mol Biol 70: 175–206.

    Article  CAS  PubMed  Google Scholar 

  • Hyde JC, Robinson N. 1978. Electron cytochemical localization of γ-aminobutyric acid catabolism in rat cerebellar cortex. Histochemistry 49: 51–65.

    Article  Google Scholar 

  • Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL, et al. 2006. Neuronal–glial glucose oxidation and glutamatergic-GABAergic function. J Cereb Blood Flow Metab 26: 865–877.

    Article  CAS  PubMed  Google Scholar 

  • Iadarola MJ, Gale K. 1980. Evaluation of increases in nerve terminal-dependent vs nerve terminal-independent compartments of GABA in vivo. Brain Res Bull 5: 13–19.

    Article  CAS  Google Scholar 

  • Iadarola MJ, Gale K. 1982. Substantia nigra: Site of anticonvulsant activity mediated by γ-aminobutyric acid. Science 218: 1237–1240.

    Article  CAS  PubMed  Google Scholar 

  • Itoh M, Uchimura H. 1981. Regional differences in cofactor saturation of glutamate decarboxylase (GAD) in discrete brain nuclei of the rat. Effect of repeated administration of haloperidol on GAD activity in the substantia nigra. Neurochem Res 6: 1283–1289.

    CAS  PubMed  Google Scholar 

  • Jitrapakdee S, Wallace JC. 1999. Structure, function and regulation of pyruvate carboxylase. Biochem J 340 (Pt 1): 1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaufman DL, Houser CR, Tobin AJ. 1991. Two forms of the γ-aminobutyric acid synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions. J Neurochem 56: 720–723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaufman DL, McGinnis JF, Krieger NR, Tobin AJ. 1986. Brain glutamate decarboxylase cloned in λgt-11: Fusion protein produces γ-aminobutyric acid. Science 232: 1138–1140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Kew JN, Kemp JA. 2005. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl) 179: 4–29.

    Article  CAS  Google Scholar 

  • Kihara M, Kubo T. 1989. Aspartate aminotransferase for synthesis of transmitter glutamate in the medulla oblongata: Effect of aminooxyacetic acid and 2-oxoglutarate. J Neurochem 52: 1127–1134.

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi Y, Kaufman DL, Tobin AJ. 1987. Glutamic acid decarboxylase cDNA: Nucleotide sequence encoding an enzymatically active fusion protein. J Neurosci 7: 2768–2772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kosenko E, Llansola M, Montoliu C, Monfort P, Rodrigo R, et al. 2003. Glutamine synthetase activity and glutamine content in brain: Modulation by NMDA receptors and nitric oxide. Neurochem Int 43: 493–499.

    Article  CAS  PubMed  Google Scholar 

  • Krogsgaard-Larsen P, Falch E, Larsson OM, Schousboe A. 1987. GABA uptake inhibitors: Relevance to antiepileptic drug research. Epilepsy Res 1: 77–93.

    Article  CAS  PubMed  Google Scholar 

  • Kvamme E, Roberg B, Johansen L, Torgner IA. 1988. Interrelated effects of calcium and sulfhydryl reagents on renal phosphate-activated glutaminase. Contrib Nephrol 63: 156–160.

    Article  CAS  PubMed  Google Scholar 

  • Kvamme E, Roberg B, Torgner IA. 2000. Phosphate-activated glutaminase and mitochondrial glutamine transport in the brain. Neurochem Res 25: 1407–1419.

    Article  CAS  PubMed  Google Scholar 

  • Kvamme E, Torgner IA, Roberg B. 2001. Kinetics and localization of brain phosphate activated glutaminase. J Neurosci Res 66: 951–958.

    Article  CAS  PubMed  Google Scholar 

  • Laake JH, Takumi Y, Eidet J, Torgner IA, Roberg B, et al. 1999. Postembedding immunogold labelling reveals subcellular localization and pathway-specific enrichment of phosphate activated glutaminase in rat cerebellum. Neuroscience 88: 1137–1151.

    Article  CAS  PubMed  Google Scholar 

  • Langeveld CH, Schepens E, Jongenelen CA, Stoof JC, Hjelle OP, et al. 1996. Presence of glutathione immunoreactivity in cultured neurones and astrocytes. Neuroreport 7: 1833–1836.

    Article  CAS  PubMed  Google Scholar 

  • Lehre KP, Danbolt NC. 1998. The number of glutamate transporter subtype molecules at glutamatergic synapses: Chemical and stereological quantification in young adult rat brain. J Neurosci 18: 8751–8757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy, LM. 2002. Structure, function and regulation of glutamate transporters. Glutamate and GABA Receptors and Transporters. Structure, Function and Pharmacology. Egebjerg J, Schousboe A, Krogsgaard-Larsen P, editors. London: Taylor and Francis, pp. 307–336.

    Google Scholar 

  • Lieth E, LaNoue KF, Berkich DA, Xu B, Ratz M, et al. 2001. Nitrogen shuttling between neurons and glial cells during glutamate synthesis. J Neurochem 76: 1712–1723.

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Beltran EA, Mate MJ, Cerdan S. 1996. Dynamics and environment of mitochondrial water as detected by 1H NMR. J Biol Chem 271: 10648–10653.

    Article  CAS  PubMed  Google Scholar 

  • Machiyama Y, Balazs R, Hammond BJ, Julian T, Richter D. 1970. The metabolism of γ-aminobutyrate and glucose in potassium ion-stimulated brain tissue in vitro. Biochem J 116: 469–481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marcaggi P, Coles JA. 2001. Ammonium in nervous tissue: Transport across cell membranes, fluxes from neurons to glial cells, and role in signalling. Prog Neurobiol 64: 157–183.

    Article  CAS  PubMed  Google Scholar 

  • Martin DL, Rimvall K. 1993. Regulation of γ-aminobutyric acid synthesis in the brain. J Neurochem 60: 395–407.

    Article  CAS  PubMed  Google Scholar 

  • Martin DL, Martin SB, Wu SJ, Espina N. 1991a. Cofactor interactions and the regulation of glutamate decarboxylase activity. Neurochem Res 16: 243–249.

    Article  CAS  PubMed  Google Scholar 

  • Martin DL, Martin SB, Wu SJ, Espina N. 1991b. Regulatory properties of brain glutamate decarboxylase (GAD): The apoenzyme of GAD is present principally as the smaller of two molecular forms of GAD in brain. J Neurosci 11: 2725–2731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mason GF, Rothman DL, Behar KL, Shulman RG. 1992. NMR determination of the TCA cycle rate and α-ketoglutarate/glutamate exchange rate in rat brain. J Cereb Blood Flow Metab 12: 434–447.

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC, Hopkins IB, Lindauer SL, Bamford P. 2006a. Aspartate aminotransferase in synaptic and nonsynaptic mitochondria: Differential effect of compounds that influence transient hetero-enzyme complex (metabolon) formation. Neurochem Int 48: 629–636.

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC, Waagepetersen HS, Schousboe A, Sonnewald U. 2006b. Neuronal and astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: Current evidence and pharmacological tools. Biochem Pharmacol 71: 399–407.

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC, Stevenson JH, Huang X, Hopkins IB. 2000a. Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals. Neurochem Int 37: 229–241.

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC, Stevenson JH, Huang X, Tildon JT, Zielke CL, et al. 2000b. Mitochondrial malic enzyme activity is much higher in mitochondria from cortical synaptic terminals compared with mitochondria from primary cultures of cortical neurons or cerebellar granule cells. Neurochem Int 36: 451–459.

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC, Tildon JT, Stevenson JH, Boatright R, Huang S. 1993. Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes: Differences revealed using aminooxyacetate. Dev Neurosci 15: 320–329.

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC, Tildon JT, Stevenson JH, Huang X. 1996a. New insights into the compartmentation of glutamate and glutamine in cultured rat brain astrocytes. Dev Neurosci 18: 380–390.

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC, Sonnewald U, Huang X, Stevenson J, Zielke HR. 1996b. Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J Neurochem 66: 386–393.

    Article  CAS  PubMed  Google Scholar 

  • Meier E, Drejer J, Schousboe A. 1984. GABA induces functionally active low-affinity GABA receptors on cultured cerebellar granule cells. J Neurochem 43: 1737–1744.

    Article  CAS  PubMed  Google Scholar 

  • Meier E, Hertz L, Schousboe A. 1991. Neurotransmitters as developmental signals. Neurochem Int 19: 1–15.

    Article  CAS  Google Scholar 

  • Meldrum BS. 2000. Glutamate as a neurotransmitter in the brain: Review of physiology and pathology. J Nutr 130: 1007S–1015S.

    Article  CAS  PubMed  Google Scholar 

  • Miller LP, Martin DL, Mazumder A, Walters JR. 1978. Studies on the regulation of GABA synthesis: Substrate-promoted dissociation of pyridoxal-5′-phosphate from GAD. J Neurochem 30: 361–369.

    Article  CAS  PubMed  Google Scholar 

  • Minchin MC, Beart PM. 1975. Compartmentation of amino acid metabolism in the rat posterior pituitary. J Neurochem 24: 881–884.

    Article  CAS  PubMed  Google Scholar 

  • Norenberg MD, Martinez-Hernandez A. 1979. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res 161: 303–310.

    Article  CAS  PubMed  Google Scholar 

  • Olsen RW, Betz H. 2006. Energy metabolism of the brain. Basic Neurochemistry: Molecular, Cellular, and Medical Aspects, 7th ed. Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD, editors. Philadelphia: Lippincott-Raven, pp. 531–557.

    Google Scholar 

  • Olstad E, Qu H, Sonnewald U. 2007. Glutamate is preferred over glutamine for intermediary metabolism in cultured cerebellar neurons. J Cereb Blood Flow Metab.

    Google Scholar 

  • O'Neal RM, Koeppe RE. 1966. Precursors in vivo of glutamate, aspartate and their derivatives of rat brain. J Neurochem 13: 835–847.

    Article  CAS  PubMed  Google Scholar 

  • Oz G, Berkich DA, Henry PG, Xu Y, La Noue K, et al. 2004. Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity. J Neurosci 24: 11273–11279.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Palaiologos G, Hertz L, Schousboe A. 1989. Role of aspartate aminotransferase and mitochondrial dicarboxylate transport for release of endogenously and exogenously supplied neurotransmitter in glutamatergic neurons. Neurochem Res 14: 359–366.

    Article  CAS  PubMed  Google Scholar 

  • Parpura V, Scemes E, Spray DC. 2004. Mechanisms of glutamate release from astrocytes: Gap junction “hemichannels”, purinergic receptors and exocytotic release. Neurochem Int 45: 259–264.

    Article  CAS  PubMed  Google Scholar 

  • Patel AB, Chowdhury GM, de Graaf RA, Rothman DL, Shulman RG, et al. 2005a. Cerebral pyruvate carboxylase flux is unaltered during bicuculline-seizures. J Neurosci Res 79: 128–138.

    Article  CAS  PubMed  Google Scholar 

  • Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG, et al. 2005b. The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Proc Natl Acad Sci USA 102: 5588–5593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel AB, de Graaf RA, Martin DL, Battaglioli G, Behar KL. 2006. Evidence that GAD65 mediates increased GABA synthesis during intense neuronal activity in vivo. J Neurochem 97: 385–396.

    Article  CAS  PubMed  Google Scholar 

  • Patel AB, de Graaf RA, Mason GF, Kanamatsu T, Rothman DL, et al. 2004. Glutamatergic neurotransmission and neuronal glucose oxidation are coupled during intense neuronal activation. J Cereb Blood Flow Metab 24: 972–985.

    Article  CAS  PubMed  Google Scholar 

  • Patel AJ, Hunt A, Gordon RD, Balazs R. 1982. The activities in different neural cell types of certain enzymes associated with the metabolic compartmentation glutamate. Brain Res 256: 3–11.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Perkins GA, Renken CW, Frey TG, Ellisman MH. 2001. Membrane architecture of mitochondria in neurons of the central nervous system. J Neurosci Res 66: 857–865.

    Article  CAS  PubMed  Google Scholar 

  • Plaitakis A, Zaganas I. 2001. Regulation of human glutamate dehydrogenases: Implications for glutamate, ammonia and energy metabolism in brain. J Neurosci Res 66: 899–908.

    Article  CAS  PubMed  Google Scholar 

  • Plaitakis A, Spanaki C, Mastorodemos V, Zaganas I. 2003. Study of structure–function relationships in human glutamate dehydrogenases reveals novel molecular mechanisms for the regulation of the nerve tissue-specific (GLUD2) isoenzyme. Neurochem Int 43: 401–410.

    Article  CAS  PubMed  Google Scholar 

  • Porter TG, Martin DL. 1987. Rapid inactivation of brain glutamate decarboxylase by aspartate. J Neurochem 48: 67–72.

    Article  CAS  PubMed  Google Scholar 

  • Preece NE, Cerdan S. 1996. Metabolic precursors and compartmentation of cerebral GABA in vigabatrin-treated rats. J Neurochem 67: 1718–1725.

    Article  CAS  PubMed  Google Scholar 

  • Qu H, Konradsen JR, van Hengel M, Wolt S, Sonnewald U. 2001. Effect of glutamine and GABA on [U-13C]glutamate metabolism in cerebellar astrocytes and granule neurons. J Neurosci Res 66: 885–890.

    Article  CAS  PubMed  Google Scholar 

  • Ramos M, del Arco A, Pardo B, Martinez- Serrano A, Martinez- Morales JR, et al. 2003. Developmental changes in the Ca2+-regulated mitochondrial aspartate–glutamate carrier aralar1 in brain and prominent expression in the spinal cord. Brain Res Dev Brain Res 143: 33–46.

    Article  CAS  PubMed  Google Scholar 

  • Reubi JC, Van den Berg CJ, Cuénod M. 1978. Glutamine as precursor for the GABA and glutamate transmitter pools. Neurosci Lett 10: 171-174.

    Google Scholar 

  • Roberts E, Bregoff HM. 1953. Transamination of γ-aminobutyric acid and β-alanine in brain and liver. J Biol Chem 201: 393–398.

    Article  CAS  PubMed  Google Scholar 

  • Rose C, Kresse W, Kettenmann H. 2005. Acute insult of ammonia leads to calcium-dependent glutamate release from cultured astrocytes, an effect of pH. J Biol Chem 280: 20937–20944.

    Article  CAS  PubMed  Google Scholar 

  • Rothe F, Brosz M, Storm-Mathisen J. 1994. Quantitative ultrastructural localization of glutamate dehydrogenase in the rat cerebellar cortex. Neuroscience 62: 1133–1146.

    Article  CAS  PubMed  Google Scholar 

  • Rothstein JD, Tabakoff B. 1984. Alteration of striatal glutamate release after glutamine synthetase inhibition. J Neurochem 43: 1438–1446.

    Article  CAS  PubMed  Google Scholar 

  • Salganicoff L, De Robertis E. 1965. Subcellular distribution of the enzymes of the glutamic acid, glutamine and γ-amino-butyric acid cycles in rat brain. J Neurochem 12: 287–309.

    Article  CAS  PubMed  Google Scholar 

  • Schousboe A, Waagepetersen HS. 2004. Role of astrocytes in homeostasis of glutamate and GABA during physiological and pathophysiological conditions. Adv Mol Cell Biol 31: 461–474.

    Article  CAS  Google Scholar 

  • Schousboe A, Hertz L, Svenneby G, Kvamme E. 1979. Phosphate-activated glutaminase activity and glutamine uptake in primary cultures of astrocytes. J Neurochem 32: 943–950.

    Article  CAS  PubMed  Google Scholar 

  • Schousboe A, Larsson OM, Seiler N. 1986. Stereoselective uptake of the GABA-transaminase inhibitors γ-vinyl GABA and γ-acetylenic GABA into neurons and astrocytes. Neurochem Res 11: 1497–1505.

    Article  CAS  PubMed  Google Scholar 

  • Schousboe A, Sarup A, Bak LK, Waagepetersen HS, Larsson OM. 2004. Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission. Neurochem Int 45: 521–527.

    Article  CAS  PubMed  Google Scholar 

  • Schousboe A, Svenneby G, Hertz L. 1977a. Uptake and metabolism of glutamate in astrocytes cultured from dissociated mouse brain hemispheres. J Neurochem 29: 999–1005.

    Article  CAS  PubMed  Google Scholar 

  • Schousboe I, Bro B, Schousboe A. 1977b. Intramitochondrial localization of the 4-aminobutyrate-2-oxoglutarate transaminase from ox brain. Biochem J 162: 303–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schousboe A, Westergaard N, Sonnewald U, Petersen SB, Huang R, et al. 1993. Glutamate and glutamine metabolism and compartmentation in astrocytes. Dev Neurosci 15: 359–366.

    Article  CAS  PubMed  Google Scholar 

  • Schousboe A, Wu JY, Roberts E. 1973. Purification and characterization of the 4-aminobutyrate-2-ketoglutarate transaminase from mouse brain. Biochemistry 12: 2868–2873.

    Article  CAS  PubMed  Google Scholar 

  • Schousboe A, Wu JY, Roberts E. 1974. Subunit structure and kinetic properties of 4-aminobutyrate-2-ketoglutarate transaminase purified from mouse brain. J Neurochem 23: 1189–1195.

    Article  CAS  PubMed  Google Scholar 

  • Schwarzer C, Sperk G. 1995. Hippocampal granule cells express glutamic acid decarboxylase-67 after limbic seizures in the rat. Neuroscience 69: 705–709.

    Article  CAS  PubMed  Google Scholar 

  • Seiler N. 1980. On the role of GABA in vertebrate polyamine metabolism. Physiol Chem Phys 12: 411–429.

    CAS  PubMed  Google Scholar 

  • Shank RP, Campbell GL. 1984. α-Ketoglutarate and malate uptake and metabolism by synaptosomes: Further evidence for an astrocyte-to-neuron metabolic shuttle. J Neurochem 42: 1153–1161.

    Article  CAS  PubMed  Google Scholar 

  • Shank RP, Baldy WJ, Ash CW. 1989. Glutamine and 2-oxoglutarate as metabolic precursors of the transmitter pools of glutamate and GABA: Correlation of regional uptake by rat brain synaptosomes. Neurochem Res 14: 371–376.

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Sheikh SN, Martin DL. 1998. Elevation of brain GABA levels with vigabatrin (γ-vinylGABA) differentially affects GAD65 and GAD67 expression in various regions of rat brain. J Neurosci Res 52: 736–741.

    Article  CAS  PubMed  Google Scholar 

  • Sibson NR, Dhankhar A, Mason GF, Behar KL, Rothman DL, et al. 1997. In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate–glutamine cycling. Proc Natl Acad Sci USA 94: 2699–2704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sibson NR, Mason GF, Shen J, Cline GW, Herskovits AZ, et al. 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  CAS  PubMed  Google Scholar 

  • Sloviter RS, Dichter MA, Rachinsky TL, Dean E, Goodman JH, et al. 1996. Basal expression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus. J Comp Neurol 373: 593–618.

    Article  CAS  PubMed  Google Scholar 

  • Soghomonian JJ, Martin DL. 1998. Two isoforms of glutamate decarboxylase: Why? Trends Pharmacol Sci 19: 500–505.

    Article  CAS  PubMed  Google Scholar 

  • Sonnewald U, Hertz L, Schousboe A. 1998. Mitochondrial heterogeneity in the brain at the cellular level. J Cereb Blood Flow Metab 18: 231–237.

    Article  CAS  PubMed  Google Scholar 

  • Sonnewald U, Westergaard N, Hassel B, Muller TB, Unsgard G, et al. 1993a. NMR spectroscopic studies of 13C acetate and 13C glucose metabolism in neocortical astrocytes: Evidence for mitochondrial heterogeneity. Dev Neurosci 15: 351–358.

    Article  CAS  PubMed  Google Scholar 

  • Sonnewald U, Westergaard N, Petersen SB, Unsgard G, Schousboe A. 1993b. Metabolism of [U-13C]glutamate in astrocytes studied by 13C NMR spectroscopy: Incorporation of more label into lactate than into glutamine demonstrates the importance of the tricarboxylic acid cycle. J Neurochem 61: 1179–1182.

    Article  CAS  PubMed  Google Scholar 

  • Sonnewald U, Westergaard N, Schousboe A, Svendsen JS, Unsgard G, et al. 1993c. Direct demonstration by [13C]NMR spectroscopy that glutamine from astrocytes is a precursor for GABA synthesis in neurons. Neurochem Int 22: 19–29.

    Article  CAS  PubMed  Google Scholar 

  • Sonnewald U, Westergaard N, Jones P, Taylor A, Bachelard HS, et al. 1996. Metabolism of [U-13C5]glutamine in cultured astrocytes studied by NMR spectroscopy: First evidence of astrocytic pyruvate recycling. J Neurochem 67: 2566–2572.

    Article  CAS  PubMed  Google Scholar 

  • Sonnewald U, Westergaard N, Krane J, Unsgard G, Petersen SB, et al. 1991. First direct demonstration of preferential release of citrate from astrocytes using [13C]NMR spectroscopy of cultured neurons and astrocytes. Neurosci Lett 128: 235–239.

    Article  CAS  PubMed  Google Scholar 

  • Sperk G, Schwarzer C, Heilman J, Furtinger S, Reimer RJ, et al. 2003. Expression of plasma membrane GABA transporters but not of the vesicular GABA transporter in dentate granule cells after kainic acid seizures. Hippocampus 13: 806–815.

    Article  CAS  PubMed  Google Scholar 

  • Szerb JC, O'Regan PA. 1985. Effect of glutamine on glutamate release from hippocampal slices induced by high K+ or by electrical stimulation: Interaction with different Ca2+ concentrations. J Neurochem 44: 1724–1731.

    Article  CAS  PubMed  Google Scholar 

  • van den Berg CJ, Garfinkel D. 1971. A stimulation study of brain compartments. Metabolism of glutamate and related substances in mouse brain. Biochem J 123: 211–218.

    CAS  PubMed  Google Scholar 

  • van den Berg CJ, Krzalic L, Mela P, Waelsch H. 1969. Compartmentation of glutamate metabolism in brain. Evidence for the existence of two different tricarboxylic acid cycles in brain. Biochem J 113: 281–290.

    CAS  PubMed  Google Scholar 

  • Varoqui H, Zhu H, Yao D, Ming H, Erickson JD. 2000. Cloning and functional identification of a neuronal glutamine transporter. J Biol Chem 275: 4049–4054.

    Article  CAS  PubMed  Google Scholar 

  • Vogel R, Hamprecht B, Wiesinger H. 1998a. Malic enzyme isoforms in astrocytes: Comparative study on activities in rat brain tissue and astroglia-rich primary cultures. Neurosci Lett 247: 123–126.

    Article  CAS  PubMed  Google Scholar 

  • Vogel R, Jennemann G, Seitz J, Wiesinger H, Hamprecht B. 1998b. Mitochondrial malic enzyme: Purification from bovine brain, generation of an antiserum, and immunocytochemical localization in neurons of rat brain. J Neurochem 71: 844–852.

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Bakken IJ, Larsson OM, Sonnewald U, Schousboe A. 1998a. Comparison of lactate and glucose metabolism in cultured neocortical neurons and astrocytes using 13C-NMR spectroscopy. Dev Neurosci 20: 310–320.

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Bakken IJ, Larsson OM, Sonnewald U, Schousboe A. 1998b. Metabolism of lactate in cultured GABAergic neurons studied by 13C nuclear magnetic resonance spectroscopy. J Cereb Blood Flow Metab 18: 109–117.

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Hansen GH, Fenger K, Lindsay JG, Gibson G, et al. 2006. Cellular mitochondrial heterogeneity in cultured astrocytes as demonstrated by immunogold labeling of α-ketoglutarate dehydrogenase. Glia 53: 225–231.

    Article  PubMed  Google Scholar 

  • Waagepetersen HS, Qu H, Hertz L, Sonnewald U, Schousboe A. 2002. Demonstration of pyruvate recycling in primary cultures of neocortical astrocytes but not in neurons. Neurochem Res 27: 1431–1437.

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Qu H, Sonnewald U, Shimamoto K, Schousboe A. 2005. Role of glutamine and neuronal glutamate uptake in glutamate homeostasis and synthesis during vesicular release in cultured glutamatergic neurons. Neurochem Int 47: 92–102

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A. 1999a. Synthesis of vesicular GABA from glutamine involves TCA cycle metabolism in neocortical neurons. J Neurosci Res 57: 342–349.

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Sonnewald U, Qu H, Schousboe A. 1999b. Mitochondrial compartmentation at the cellular level: Astrocytes and neurons. Ann NY Acad Sci 893: 421–425.

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A. 2000. A possible role of alanine for ammonia transfer between astrocytes and glutamatergic neurons. J Neurochem 75: 471–479.

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A. 2001a. Multiple compartments with different metabolic characteristics are involved in biosynthesis of intracellular and released glutamine and citrate in astrocytes. Glia 35: 246–252.

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Sonnewald U, Gegelashvili G, Larsson OM, Schousboe A. 2001b. Metabolic distinction between vesicular and cytosolic GABA in cultured GABAergic neurons using 13C magnetic resonance spectroscopy. J Neurosci Res 63: 347–355.

    Article  CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Sonnewald U, Schousboe A. 2003. Compartmentation of glutamine, glutamate, and GABA metabolism in neurons and astrocytes: Functional implications. Neuroscientist 9: 398–403.

    Article  CAS  PubMed  Google Scholar 

  • Wadiche JI, Arriza JL, Amara SG, Kavanaugh MP. 1995. Kinetics of a human glutamate transporter. Neuron 14: 1019–1027.

    Article  CAS  PubMed  Google Scholar 

  • Westergaard N, Drejer J, Schousboe A, Sonnewald U. 1996. Evaluation of the importance of transamination versus deamination in astrocytic metabolism of [U-13C]glutamate. Glia 17: 160–168.

    Article  CAS  PubMed  Google Scholar 

  • Westergaard N, Sonnewald U, Petersen SB, Schousboe A. 1995. Glutamate and glutamine metabolism in cultured GABAergic neurons studied by 13C NMR spectroscopy may indicate compartmentation and mitochondrial heterogeneity. Neurosci Lett 185: 24–28.

    Article  CAS  PubMed  Google Scholar 

  • Westergaard N, Sonnewald U, Schousboe A. 1994a. Release of α-ketoglutarate, malate and succinate from cultured astrocytes: Possible role in amino acid neurotransmitter homeostasis. Neurosci Lett 176: 105–109.

    Article  CAS  PubMed  Google Scholar 

  • Westergaard N, Sonnewald U, Unsgard G, Peng L, Hertz L, et al. 1994b. Uptake, release, and metabolism of citrate in neurons and astrocytes in primary cultures. J Neurochem 62: 1727–1733.

    Article  CAS  PubMed  Google Scholar 

  • Wood JD, Kurylo E, Tsui SK. 1981. Interactions of di-n-propylacetate, gabaculine, and aminooxyacetic acid: Anticonvulsant activity and the γ-aminobutyrate system. J Neurochem 37: 1440–1447.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Yu AC, Fisher TE, Hertz E, Tildon JT, Schousboe A, et al. 1984. Metabolic fate of [14C]-glutamine in mouse cerebral neurons in primary cultures. J Neurosci Res 11: 351–357.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Yudkoff M, Daikhin Y, Grunstein L, Nissim I, Stern J, et al. 1996. Astrocyte leucine metabolism: Significance of branched-chain amino acid transamination. J Neurochem 66: 378–385.

    Article  CAS  PubMed  Google Scholar 

  • Yudkoff M, Nelson D, Daikhin Y, Erecinska M. 1994. Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate/aspartate shuttle. J Biol Chem 269: 27414–27420.

    CAS  PubMed  Google Scholar 

  • Yudkoff M, Nissim I, Hertz L. 1990. Precursors of glutamic acid nitrogen in primary neuronal cultures: Studies with 15N. Neurochem Res 15: 1191–1196.

    Article  CAS  PubMed  Google Scholar 

  • Yudkoff M, Nissim I, Pleasure D, 1988. Astrocyte metabolism of [15N]glutamine: Implications for the glutamine–glutamate cycle. J Neurochem 51: 843–850.

    Article  CAS  PubMed  Google Scholar 

  • Zieminska E, Hilgier W, Waagepetersen HS, Hertz L, Sonnewald U, et al. 2004. Analysis of glutamine accumulation in rat brain mitochondria in the presence of a glutamine uptake inhibitor, histidine, reveals glutamine pools with a distinct access to deamidation. Neurochem Res 29: 2121–2123.

    Article  CAS  PubMed  Google Scholar 

Download references

Authors
  1. H. S. Waagepetersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U. Sonnewald
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Schousboe
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New york, USA

    Abel Lajtha (Director) (Director)

  2. The Centre for Laboratory Medicine, Tampere University Hospital, PB 2000, FI-33520, Tampere, Finland

    Simo S. Oja

  3. Inst. for Pharmacology, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark

    Arne Schousboe

  4. Brain Research Center, Medical School, University of Tampere, FI-33014, Espoo, Finland

    Pirjo Saransaari

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC

About this entry

Cite this entry

Waagepetersen, H.S., Sonnewald, U., Schousboe, A. (2007). 1 Glutamine, Glutamate, and GABA: Metabolic Aspects. In: Lajtha, A., Oja, S.S., Schousboe, A., Saransaari, P. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30373-4_1

Download citation

Publish with us

Policies and ethics

Search

Navigation