Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation

Journal of Cerebral Blood Flow and Metabolism

Volumn 31, Issue 1, 2011, Pages 90-101

  Pardo, Beatriz ^a   Rodrigues, Tiago B ^b,c   Contreras, Laura ^a   Garzón, Miguel ^a,f   Llorente Folch, Irene ^a   Kobayashi, Keiko ^d   Saheki, Takeyori ^e   Cerdan, Sebastian ^b   Satrüstegui, Jorgina ^a  

^a UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^b INSTITUTO DE INVESTIGACIONES BIOMÉDICAS ALBERTO SOLS   (Spain)

^c UNIVERSITY OF COIMBRA   (Portugal)

^d KAGOSHIMA UNIVERSITY   (Japan)

^e TOKUSHIMA BUNRI UNIVERSITY   (Japan)

^f UNIVERSITY OF PADOVA   (Italy)

Author keywords

AGC1; Aralar; aspartate; glial glutamine; mitochondrial aspartate glutamate carrier; OmniBank

Indexed keywords

ASPARTIC ACID; GLUTAMIC ACID; GLUTAMINE; LACTIC ACID; PYRUVIC ACID;

AMINO ACID SYNTHESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ARALAR GENE; ARTICLE; ASTROCYTE; BRAIN METABOLISM; COMPARATIVE STUDY; CONTROLLED STUDY; GENE; GLIA CELL; ISOTOPE LABELING; MALE; MOUSE; NERVE CELL CULTURE; NONHUMAN; PRIORITY JOURNAL;

ALANINE; ANIMALS; ASPARTIC ACID; ASTROCYTES; BRAIN CHEMISTRY; CELLS, CULTURED; FLUORESCENT ANTIBODY TECHNIQUE; GAMMA-AMINOBUTYRIC ACID; GLUCOSE; GLUTAMIC ACID; GLUTAMINE; IMMUNOHISTOCHEMISTRY; LACTIC ACID; LEUCINE; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROSCOPY, ELECTRON; NEURONS; NITROGEN; PYRUVIC ACID;

EID: 78650897135     PISSN: 0271678X     EISSN: None     Source Type: Journal    
DOI: 10.1038/jcbfm.2010.146     Document Type: Article

References (46)

1. Aureli T, Di Cocco ME, Calvani M, Conti F (1997) The entry of [1-13C]glucose into biochemical pathways reveals a complex compartimentation and metabolite trafficking between glia and neurons: a study by 13C-NMR spectroscopy. Brain Res 765:218-27
2. Bak LK, Schousboe A, Waagepetersen HS (2006) The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem 98:641-53
3. Berkich DA, Ola MS, Cole J, Sweatt AJ, Hutson SM, LaNoue KF (2007) Mitochondrial transport proteins of the brain. J Neurosci Res 85:3367-77
4. Bröer S, Bröer A, Hansen JT, Bubb WA, Balcar VJ, Nasrallah FA, Garner B, Rae C (2007) Alanine metabolism, transport, and cycling in the brain. J Neurochem 102:1758-70
5. Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Krieg PA, Krupenko SA, Thompson WJ, Barres BA (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci 28:264-78
6. Cerdán S, Künnecke B, Seelig J (1990) Cerebral metabolism of [1,2-13C2] acetate as detected by in vivo and in vitro 13C NMR. J Biol Chem 265:12916-26
7. Chapa F, Garća-Mart́n ML, Garća-Espinosa MA, Cerdan S (2000) Metabolism of (1-13C) glucose and (2-13C, 2-2H3) acetate in the neuronal and glial compartments of the adult rat brain as detected by [13C, 2H] NMR spectroscopy. Neurochem Int 37:217-28
8. Coetzee T, Fujita N, Dupree J, Shi R, Blight A, Suzuki K, Suzuki K, Popko B (1996) Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability. Cell 86: 209-19
9. Contreras L, Urbieta A, Kobayashi K, Saheki T, Satrú stegui J (2010) Low levels of citrin (SLC25A13) expression in adult mouse brain restricted to neuronal clusters. J Neurosci Res 88:1009-16
10. Cruz F, Cerdán S (1999) Quantitative 13C NMR studies of metabolic compartmentation in the adult mammalian brain. NMR Biomed 12:451-62
11. Erecinska M, Pleasure D, Nelson D, Nissim I, Yudkoff M (1993) Cerebral aspartate utilization: near-equilibrium relationships in aspartate aminotransferase reaction. J Neurochem 60:1696-706
12. Gamberino WC, Berkich DA, Lynch CJ, Xu B, LaNoue KF (2007) Role of pyruvate carboxylase in facilitation of synthesis of glutamate and glutamine in cultured astrocytes. J Neurochem 69:2312-25
13. Goldlust A, Su TZ, Welty DF, Taylor CP, Oxender DL (1995) Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. Epilepsy Res 22:1-11
14. Herrero-Mendez A, Almeida A, Fernández E, Maestre C, Moncada S, Bolañ os JP (2009) The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/CCdh1. Nat Cell Biol 11:747-52
15. Hertz L, Kala G (2007) Energy metabolism in brain cells: effects of elevated ammonia concentrations. Metab Brain Dis 22:199-218
16. Jalil MA, Begun L, Contreras L, Pardo B, Iijima M, Li MX, Ramos M, Marmol P, Horiuchi M, Shimotsu K, Nakagawa S, Okubo A, Sameshima M, Isashiki Y, del Arco A, Kobayashi K, Satrú stegui J, Saheki T (2005) Reduced N-acetylaspartate levels in mice lacking aralar, a brainand muscle-type mitochondrial aspartate-glutamate carrier. J Biol Chem 280:31333-9
17. Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW (2004) Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305:99-103
18. Lieth E, LaNoue KF, Berkich DA, Xu B, Ratz M, Taylor C, Hutson SM (2001) Nitrogen shuttling between neurons and glial cells during glutamate synthesis. J Neurochem 76:1712-3
19. Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH, Han X, Takano T, Wang S, Sim FJ, Goldman SA, Nedergaard M (2007) The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci 27:12255-66
20. Kanner BI (2006) Structure and function of sodiumcoupled GABA and glutamate transporters. J Membrane Biol 213:89-100
21. Madhavarao CN, Moffett JR, Moore RA, Viola RE, Namboodiri MA, Jacobowitz DM (2004) Immunohistochemical localization of aspartoacylase in the rat central nervous system. J Comp Neurol 472:318-29
22. Mart́nez-Hernandez A, Bell KP, Norenberg MD (1977) Glutamine synthetase: glial localization in brain. Science 195:1356-8
23. 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 15:320-9
24. McKenna MC, Sonnewald U, Huang X, Stevenson J, Zielke HR (1996) Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J Neurochem 66:386-93
25. McKenna MC (2007) The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in the brain. J Neurosci Res 85:3347-58
26. Miyaji T, Echigo N, Senoh S, Omote H, Moriyama Y (2008) Identification of a vesicular aspartate transporter. Proc Natl Acad Sci USA 105:11720-4
27. Navarro D, Zwingmann C, Butterworth RF (2008) Region selective alterations of glucose oxidation and amino acid synthesis in the thiamine-deficient rat brain: re-evaluation using 1H/13C nuclear magnetic resonance spectroscopy. J Neurochem 106:603-12
28. Palaiologos G, Hertz L, Schousboe A (1988) Evidence that aspartate aminotransferase activity and ketodicarboxylate carrier function are essential for biosynthesis of transmitter glutamate. J Neurochem 51:317-20
29. Preece NE, Cerdán S (1996) Metabolic precursors and compartimentation of cerebral GABA in vigabatrintreated rats. J Neurochem 67:1718-25
30. Price MT, Pusateri ME, Crow SE, Buchsbaum S, Olney JW, Lowry OH (1984) Uptake of exogenous aspartate into circumventricular organs but not other regions of adult mouse brain. J Neurochem 42:740-4
31. Ramos M, del Arco A, Pardo B, Mart́nez-Serrano A, Mart́nez-Morales JR, Kobayashi K, Yasuda T, Bogónez E, Bovolenta P, Saheki T, Satrú stegui J (2003) Developmental changes in the Ca2+-regulated mitochondrial aspartateglutamate carrier aralar1 in brain and prominent expression in the spinal cord. Dev Brain Res 143:33-46
32. Rodrigues TB, Granado N, Ortiz O, Cerdán S, Moratalla R (2007) Metabolic interactions between glutamatergic and dopaminergic neurotransmitter systems are mediated through D1 dopamine receptors. J Neurosci Res 85:3284-93
33. Rothman DL, Behar KL, Hyder F, Shulman RG (2003) In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Ann Rev Physiol 65:401-27
34. Schousboe A (1981) Transport and metabolism of glutamate and GABA in neurons and glial cells. Int Rev Neurobiol 22:1-45
35. Schousboe A, Westergaard N, Sonnewald U, Petersen SB, Huang R, Peng L, Hertz L (1993) Glutamate and glutamine metabolism and compartmentation in astrocytes. Dev Neurosci 15:359-66
36. Shank RP, Bennet GS, Freytag SO, Campbell GL (1985) Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid pools. Brain Res 329:364-7
37. She P, Reid TM, Bronson SK, Vary TC, Hajnal A, Lynch CJ, Hutson SM (2007) Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab 6:181-94
38. Sonnewald U, Westergaard N, Petersen SB, Unsgard G, Schousboe A (1993) 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 61:1179-82
39. Urenjak J, Williams SR, Gadian DG, Noble M (1993) Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13:981-9
40. Waniewski RA, Martin DL (1998) Preferential utilization of acetate by astrocytes is attributable to transport. J Neurosci 18:5225-33
41. Westergaard N, Sonnewald U, Schousboe A (1994) Release of alpha-ketoglutarate, malate and succinate from cultured astrocytes: possible role in amino acid neurotransmitter homeostasis. Neurosci Lett 176:105-9
42. Wibom R, Lasorsa FM, Töhönen V, Barbaro M, Sterky FH, Kucinski T, Naess K, Jonsson M, Pierri CL, Palieri F, Wedell A (2009) AGC1 deficiency associated with global cerebral hypomyelination. New Engl J Med 361:489-95
43. 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 101:120-31
44. Yudkoff M, Nissim I, Hummeler K, Medow M, Pleasure D (1986) Utilization of [15N] glutamate by cultured astrocytes. Biochem J 234:185-92
45. Yudkoff M, Nissim I, Pleasure D (1987) [15N]aspartate metabolism in cultured astrocytes. Studies with gas chromatography-mass spectrometry. Biochem J 241: 193-201
46. Yudkoff M, Daikhin Y, Grunstein L, Nissim I, Stern J, Pleasure D, Nissim I (1996) Astrocyte leucine metabolism: significance of branched-chain amino acid transamination. J Neurochem 66:378-85