Skip to main content
SpringerLink
Log in
Book cover

Neural Metabolism In Vivo pp 715–753Cite as

Pyruvate Transport and Metabolism in the Central Nervous System

  • Chapter
  • First Online:

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 4))

Abstract

We review the transport and enzyme systems involved in cerebral ­pyruvate metabolism, combining the information derived from recent genome sequencing technologies and in vivo or in vitro 13C and (13C, 2H) NMR approaches. Emphasis is placed on the role of subcellular compartmentation in the metabolic coupling between neurons and glial cells during glutamatergic neurotransmission. Proton-linked monocarboxylate transport through the plasma membrane utilizes the monocarboxylate transporters MCT as coded by the family of SLC16 genes, of which MCT4 and MCT2 are found in astrocytes and neurons, respectively. Cytosolic metabolism of monocarboxylates is kinetically compartmented in neurons and astrocytes with two different pyruvate pools originated from extracellular glucose or monocarboxylates, respectively. Mitochondrial transport of pyruvate is mediated by the pyruvate carrier PyC, a member of the mitochondrial carrier proteins, coded by the SLC25 gene family. Intramitochondrial oxidation of pyruvate in the cerebral tricarboxylic acid cycle is mainly controlled by pyruvate dehydrogenase, an ubiquitous multienzyme complex. Pyruvate carboxylase, an exclusively astrocytic enzyme, plays a fundamental anaplerotic role replenishing the glutamate and GABA pools involved in neurotransmission. Recent results obtained with cerebral mitochondria, primary cultures of neurons and astrocytes or in the in vivo brain with (13C,2H) NMR have revealed the presence of two kinetically different glutamate pools in neurons and astrocytes. The subcellular compartmentation of glutamate and pyruvate were not considered in previous interpretations of metabolic coupling between neurons and glial cells in vivo. To account for these findings we proposed a novel redox coupling mechanism incorporating intracellular glutamate and monocarboxylate compartmentation. Transcellular redox coupling is based on: (a) the intracellular coupling of glycolysis and oxidation in neurons and astrocytes through NAD(P)/NAD(P)H redox switches, (b) the transcellular coupling of NAD(P)/NAD(P)H redox states in neurons and glial cells through the intercellular exchange of monocarboxylate reducing equivalents and (c) the glutamate-glutamine cycle, exchanging only the cytosolic (or vesicular) pools of glutamate and glutamine in both neural cells.

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   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

References

  • Aevarsson A, Chuang JL, Wynn RM, Turley S, Chuang DT, Hol WGJ (2000) Cristal structure of human branched-chain a-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup disease. Structure 8:277–291

    Article  PubMed  CAS  Google Scholar 

  • Aquila H, Misra D, Eulitz M, Klingenberg M (1982) Complete amino acid sequence of the ADP/ATP carrier from beef heart mitochondria. Hoppe Seylers Z Physiol Chem 363:345–349

    Article  PubMed  CAS  Google Scholar 

  • Arco AD, Satrustegui J (2005) New mitochondrial carriers: an overview. Cell Mol Life Sci 62:2204–2227

    Article  PubMed  CAS  Google Scholar 

  • Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M, Golman K (2003) Increase in signal-to-noise ratio of  >  10,000 times in liquid-state NMR. Proc Natl Acad Sci USA 100:10158–10163

    Article  PubMed  CAS  Google Scholar 

  • Attwood PV (1995) The structure and the mechanism of action of pyruvate carboxylase. Int J Biochem Cell Biol 27:231–249

    Article  PubMed  CAS  Google Scholar 

  • Attwood PV, Keech DB (1984) Pyruvate carboxylase. Curr Top Cell Regul 23:1–55

    PubMed  CAS  Google Scholar 

  • Bachelard HS (1989) Measurement of carbohydrates and their derivatives in neuronal tissues. In: Boulton AA, Baker GB, Butterworth RF (eds) Carbohydrates and energy metabolism. Humana Press, Clifton, pp 133–154

    Chapter  Google Scholar 

  • Bachelard HS, Lewis LD, Ponten U, Siesjo BK (1974) Mechanisms activating glycolysis in the brain in arterial hypoxia. J Neurochem 22:395–401

    Article  PubMed  CAS  Google Scholar 

  • Bachelard H, Badar-Goffer R, Ben-Yoseph O, Morris P, Thatcher N (1993) Studies on metabolic regulation using NMR spectroscopy. Dev Neurosci 15:207–215

    Article  PubMed  CAS  Google Scholar 

  • Badar-Goffer RS, Bachelard HS, Morris PG (1990) Cerebral metabolism of acetate and glucose studied by 13C-n.m.r. spectroscopy. A technique for investigating metabolic compartmentation in the brain. Biochem J 266:133–139

    PubMed  CAS  Google Scholar 

  • Badar-Goffer RS, Ben-Yoseph O, Bachelard HS, Morris PG (1992) Neuronal-glial metabolism under depolarizing conditions. A 13C-n.m.r. study. Biochem J 282(Pt 1):225–230

    PubMed  CAS  Google Scholar 

  • Bell JE, Hume R, Busuttil A, Burchell A (1993) Immunocytochemical detection of the microsomal glucose-6-phosphatase in human brain astrocytes. Neuropathol Appl Neurobiol 19:429–435

    Article  PubMed  CAS  Google Scholar 

  • Ben-Yoseph O, Badar-Goffer RS, Morris PG, Bachelard HS (1993) Glycerol 3-phosphate and lactate as indicators of the cerebral cytoplasmic redox state in severe and mild hypoxia respectively: a 13C- and 31P-n.m.r. study. Biochem J 291(Pt 3):915–919

    PubMed  CAS  Google Scholar 

  • Berkich DA, Xu Y, Lanoue KF, Gruetter R, Hutson SM (2005) Evaluation of brain mitochondrial glutamate and alpha-ketoglutarate transport under physiologic conditions. J Neurosci Res 79:106–113

    Article  PubMed  CAS  Google Scholar 

  • Bernard-Helary K, Ardourel M, Magistretti P, Hevor T, Cloix JF (2002a) Stable transfection of cDNAs targeting specific steps of glycogen metabolism supports the existence of active gluconeogenesis in mouse cultured astrocytes. Glia 37:379–382

    Article  PubMed  Google Scholar 

  • Bernard-Helary K, Ardourel MY, Hevor T, Cloix JF (2002b) In vivo and in vitro glycogenic effects of methionine sulfoximine are different in two inbred strains of mice. Brain Res 929:147–155

    Article  PubMed  CAS  Google Scholar 

  • Bittar PG, Charnay Y, Pellerin L, Bouras C, Magistretti PJ (1996) Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. J Cereb Blood Flow Metab 16:1079–1089

    Article  PubMed  CAS  Google Scholar 

  • Bluml 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 

  • Bolli R, Nalecz KA, Azzi A (1989) Monocarboxylate and alpha-ketoglutarate carriers from bovine heart mitochondria. Purification by affinity chromatography on immobilized 2-cyano-4-­hydroxycinnamate. J Biol Chem 264:18024–18030

    PubMed  CAS  Google Scholar 

  • Bonavita V, Ponte F, Amore G (1964) Lactate dehydrogenase isoenzymes in the nervous tissue. Iv. An ontogenetic study on the rat brain. J Neurochem 11:39–47

    Article  PubMed  CAS  Google Scholar 

  • Brooks GA (2002) Lactate shuttles in nature. Biochem Soc Trans 30:258–264

    Article  PubMed  CAS  Google Scholar 

  • Brooks GA, Dubouchaud H, Brown M, Sicurello JP, Butz CE (1999) Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle. Proc Natl Acad Sci USA 96:1129–1134

    Article  PubMed  CAS  Google Scholar 

  • Butterworth RF, Giguere JF (1984) Pyruvate dehydrogenase activity in regions of the rat brain during postnatal development. J Neurochem 43:280–282

    Article  PubMed  CAS  Google Scholar 

  • Cerdan S (2003) 13C NMR and cerebral biochemistry. NMR Biomed 16:301–302

    Article  PubMed  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

    PubMed  CAS  Google Scholar 

  • Cerdan S, Rodrigues TB, Ballesteros P, Lopez P, Perez-Mayoral E (2003) The subcellular metabolism of water and its implications for magnetic resonance image contrast. In: Belton PS, Gil AM, Webb GA, Rutledge D (eds) Magnetic resonance in food science. Royal Society of Chemistry, Oxford, pp 121–135

    Chapter  Google Scholar 

  • Cerdan S, Rodrigues TB, Sierra A, Benito M, Fonseca LL, Fonseca CP, Garcia-Martin ML (2006) The redox switch/redox coupling hypothesis. Neurochem Int 48:523–530

    Article  PubMed  CAS  Google Scholar 

  • Cerdan S, Sierra A, Fonseca LL, Ballesteros P, Rodrigues TB (2009) The turnover of the H3 ­deuterons from (2-13C) glutamate and (2-13C) glutamine reveals subcellular trafficking in the brain of partially deuterated rats. J Neurochem 109(Suppl 1):63–72

    Article  PubMed  CAS  Google Scholar 

  • Chang GG, Tong L (2003) Structure and function of malic enzymes, a new class of oxidative decarboxylases. Biochemistry 42:12721–12733

    Article  PubMed  CAS  Google Scholar 

  • Chapa F, Kunnecke B, Calvo R, Escobar del Rey F, Morreale de Escobar G, Cerdan S (1995) Adult-onset hypothyroidism and the cerebral metabolism of (1,2-13C2) acetate as detected by 13C nuclear magnetic resonance. Endocrinology 136:296–305

    Article  PubMed  CAS  Google Scholar 

  • Chapa F, Cruz F, Garcia-Martin ML, Garcia-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 37:217–228

    Article  PubMed  CAS  Google Scholar 

  • Chhina N, Kuestermann E, Halliday J, Simpson LJ, Macdonald IA, Bachelard HS, Morris PG (2001) Measurement of human tricarboxylic acid cycle rates during visual activation by 13C magnetic resonance spectroscopy. J Neurosci Res 66:737–746

    Article  PubMed  CAS  Google Scholar 

  • Chou WY, Huang SM, Liu YH, Chang GG (1994) Cloning and expression of pigeon liver cytosolic NADP+-dependent malic enzyme cDNA and some of its abortive mutants. Arch Biochem Biophys 310:158–166

    Article  PubMed  CAS  Google Scholar 

  • Clark JB, Lai JCK (1989) Glycolytic, tricarboxylic acid cycle and related enzymes in brain. In: Boulton AA, Baker GB, Butterworth RF (eds) Carbohydrates and energy metabolism. Humana Press, Clifton, pp 233–281

    Chapter  Google Scholar 

  • Clark JB, Bates TE, Cullingford T, Land JM (1993) Development of enzymes of energy metabolism in the neonatal mammalian brain. Dev Neurosci 15:174–180

    Article  PubMed  CAS  Google Scholar 

  • Clark JB, Bates TE, Almeida A, Cullingford T, Warwick J (1994) Energy metabolism in the developing mammalian brain. Biochem Soc Trans 22:980–983

    PubMed  CAS  Google Scholar 

  • Clarke DD, Lajhta AL, Maker HS (1989a) Intermediary metabolism. In: Siegel G, Agranoff B, Albers RW, Molinoff P (eds) Basic neurochemistry. Raven, New York, pp 541–564

    Google Scholar 

  • Clarke DD, Lajtha AL, Maker HS (1989b) Intermediary metabolism. In: Siegel G, Agranof B, Albers RW, Molinoff P (eds) Basic neurochemistry. Raven, New York

    Google Scholar 

  • Consortium IHGS (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  Google Scholar 

  • Consortium MGS (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562

    Article  CAS  Google Scholar 

  • Cremer JE, Cunningham VJ, Pardridge WM, Braun LD, Oldendorf WH (1979) Kinetics of blood-brain barrier transport of pyruvate, lactate and glucose in suckling, weanling and adult rats. J Neurochem 33:439–445

    Article  PubMed  CAS  Google Scholar 

  • Crone C, Sorensen SC (1970) The permeability of the blood-brain barrier to lactate and pyruvate. Acta Physiol Scand 80:47A

    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 

  • Cruz F, Scott SR, Barroso I, Santisteban P, Cerdan S (1998) Ontogeny and cellular localization of the pyruvate recycling system in rat brain. J Neurochem 70:2613–2619

    Article  PubMed  CAS  Google Scholar 

  • Cruz F, Villalba M, Garcia-Espinosa MA, Ballesteros P, Bogonez E, Satrustegui J, Cerdan S (2001) Intracellular compartmentation of pyruvate in primary cultures of cortical neurons as detected by 13C NMR spectroscopy with multiple 13C labels. J Neurosci Res 66:771–781

    Article  PubMed  CAS  Google Scholar 

  • Cruz NF, Lasater A, Zielke HR, Dienel GA (2005) Activation of astrocytes in brain of conscious rats during acoustic stimulation: acetate utilization in working brain. J Neurochem 92:934–947

    Article  PubMed  CAS  Google Scholar 

  • Cullingford TE, Clark JB, Phillips IR (1994) The pyruvate dehydrogenase complex: cloning of the rat somatic E1 alpha subunit and its coordinate expression with the mRNAs for the E1 beta, E2, and E3 catalytic subunits in developing rat brain. J Neurochem 62:1682–1690

    Article  PubMed  CAS  Google Scholar 

  • Dawson DM, Goodfriend TL, Kaplan NO (1964) Lactic dehydrogenases: functions of the two types rates of synthesis of the two major forms can be correlated with metabolic differentiation. Science 143:929–933

    Article  PubMed  CAS  Google Scholar 

  • Day SE, Kettunen MI, Gallagher FA, Hu DE, Lerche M, Wolber J, Golman K, Ardenkjaer-Larsen JH, Brindle KM (2007) Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat Med 13:1382–1387

    Article  PubMed  CAS  Google Scholar 

  • De Meirleir L (2002) Defects of pyruvate metabolism and the Krebs cycle. J Child Neurol 17(Suppl 3):3S26-33, discussion 23S33-24

    Google Scholar 

  • del Arco A, Satrustegui J (1998) Molecular cloning of Aralar, a new member of the mitochondrial carrier superfamily that binds calcium and is present in human muscle and brain. J Biol Chem 273:23327–23334

    Article  PubMed  Google Scholar 

  • del Arco A, Satrustegui J (2004) Identification of a novel human subfamily of mitochondrial carriers with calcium-binding domains. J Biol Chem 279:24701–24713

    Article  PubMed  CAS  Google Scholar 

  • Denton RM, Halestrap AP (1979) Regulation of pyruvate metabolism in mammalian tissues. Essays Biochem 15:37–77

    PubMed  CAS  Google Scholar 

  • Desagher S, Glowinski J, Premont J (1997) Pyruvate protects neurons against hydrogen peroxide-induced toxicity. J Neurosci 17:9060–9067

    PubMed  CAS  Google Scholar 

  • Dienel GA (2002) Energy generation in the central nervous system. In: Edvinsson L, Krause DN (eds) Cerebral blood flow and metabolism. Lippincott Williams & Wilkins, Philadelphia, pp 141–171

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Dringen R, Schmoll D, Cesar M, Hamprecht B (1993) Incorporation of radioactivity from [14C]lactate into the glycogen of cultured mouse astroglial cells. Evidence for gluconeogenesis in brain cells. Biol Chem Hoppe Seyler 374:343–347

    Article  PubMed  CAS  Google Scholar 

  • Dwyer DS, Vannucci SJ, Simpson IA (2002) Expression, regulation, and functional role of glucose transporters (GLUTs) in brain. Int Rev Neurobiol 51:159–188

    Article  PubMed  CAS  Google Scholar 

  • Enerson BE, Drewes LR (2003) Molecular features, regulation, and function of monocarboxylate transporters: implications for drug delivery. J Pharm Sci 92:1531–1544

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Everse J, Kaplan NO (1973) Lactate dehydrogenases: structure and function. Adv Enzymol Relat Areas Mol Biol 37:61–133

    PubMed  CAS  Google Scholar 

  • Fayol L, Baud O, Monier A, Pellerin L, Magistretti P, Evrard P, Verney C (2004) Immunocytochemical expression of monocarboxylate transporters in the human visual cortex at midgestation. Brain Res Dev Brain Res 148:69–76

    Article  PubMed  CAS  Google Scholar 

  • Fitzpatrick SM, Hetherington HP, Behar KL, Shulman RG (1990) The flux from glucose to glutamate in the rat brain in vivo as determined by 1H-observed, 13C-edited NMR spectroscopy. J Cereb Blood Flow Metab 10:170–179

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Garcia-Espinosa MA, Garcia-Martin ML, Cerdan S (2003) Role of glial metabolism in diabetic encephalopathy as detected by high resolution 13C NMR. NMR Biomed 16:440–449

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Espinosa MA, Rodrigues TB, Sierra A, Benito M, Fonseca C, Gray HL, Bartnik BL, Garcia-Martin ML, Ballesteros P, Cerdan S (2004) Cerebral glucose metabolism and the glutamine cycle as detected by in vivo and in vitro 13C NMR spectroscopy. Neurochem Int 45:297–303

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Martin ML, Ballesteros P, Cerdan S (2001) The metabolism of water in cells and tissues as detected by NMR methods. Prog Nucl Mag Res Spectroscopy 39:41–77

    Article  CAS  Google Scholar 

  • Garcia-Martin ML, Garcia-Espinosa MA, Ballesteros P, Bruix M, Cerdan S (2002) Hydrogen turnover and subcellular compartmentation of hepatic [2-13C]glutamate and [3-13C]aspartate as detected by 13C NMR. J Biol Chem 277:7799–7807

    Article  PubMed  CAS  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 Chem 241:3918–3929

    PubMed  CAS  Google Scholar 

  • Golman K, in’t Zandt R, Thaning M (2006) Real-time metabolic imaging. Proc Natl Acad Sci USA 103:11270–11275

    Article  PubMed  CAS  Google Scholar 

  • Gruetter R (2002) In vivo 13C NMR studies of compartmentalized cerebral carbohydrate metabolism. Neurochem Int 41:143–154

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Gruetter R, Adriany G, Choi IY, Henry PG, Lei H, Oz G (2003) Localized in vivo 13C NMR spectroscopy of the brain. NMR Biomed 16:313–338

    Article  PubMed  CAS  Google Scholar 

  • Halestrap AP, Meredith D (2004) The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 447:619–628

    Article  PubMed  CAS  Google Scholar 

  • Halestrap AP, Price NT (1999) The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 343(Pt 2):281–299

    Article  PubMed  CAS  Google Scholar 

  • Hassel B (2000) Carboxylation and anaplerosis in neurons and glia. Mol Neurobiol 22:21–40

    Article  PubMed  CAS  Google Scholar 

  • Hassel B (2001) Pyruvate carboxylation in neurons. J Neurosci Res 66:755–762

    Article  PubMed  CAS  Google Scholar 

  • Hassel B, Brathe A (2000) Cerebral metabolism of lactate in vivo: evidence for neuronal pyruvate carboxylation. J Cereb Blood Flow Metab 20:327–336

    Article  PubMed  CAS  Google Scholar 

  • Hassel B, Sonnewald U (1995) Glial formation of pyruvate and lactate from TCA cycle intermediates: implications for the inactivation of transmitter amino acids? J Neurochem 65:2227–2234

    Article  PubMed  CAS  Google Scholar 

  • Heeger DJ, Ress D (2002) What does fMRI tell us about neuronal activity. Nat Rev Neurosci 3:142–151

    Article  PubMed  CAS  Google Scholar 

  • Hevor TK (1994) Some aspects of carbohydrate metabolism in the brain. Biochimie 76:111–120

    Article  PubMed  CAS  Google Scholar 

  • Hyder F, Chase JR, Behar KL, Mason GF, Siddeek M, Rothman DL, Shulman RG (1996) Increased tricarboxylic acid cycle flux in rat brain during forepaw stimulation detected with 1H[13C]NMR. Proc Natl Acad Sci USA 93:7612–7617

    Article  PubMed  CAS  Google Scholar 

  • Hyder F, Rothman DL, Mason GF, Rangarajan A, Behar KL, Shulman RG (1997) Oxidative glucose metabolism in rat brain during single forepaw stimulation: a spatially localized 1H[13C] nuclear magnetic resonance study. J Cereb Blood Flow Metab 17:1040–1047

    Article  PubMed  CAS  Google Scholar 

  • Izumi Y, Katsuki H, Zorumski CF (1997) Monocarboxylates (pyruvate and lactate) as alternative energy substrates for the induction of long-term potentiation in rat hippocampal slices. Neurosci Lett 232:17–20

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Jitrapakdee S, Booker GW, Cassady AI, Wallace JC (1996a) Cloning, sequencing and expression of rat liver pyruvate carboxylase. Biochem J 316(Pt 2):631–637

    PubMed  CAS  Google Scholar 

  • Jitrapakdee S, Walker ME, Wallace JC (1996b) Identification of novel alternatively spliced pyruvate carboxylase mRNAs with divergent 5′-untranslated regions which are expressed in a tissue-specific manner. Biochem Biophys Res Commun 223:695–700

    Article  PubMed  CAS  Google Scholar 

  • Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP (2000) CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J 19:3896–3904

    Article  PubMed  CAS  Google Scholar 

  • Kunnecke B, Cerdan S, Seelig J (1993) Cerebral metabolism of [1,2-13C2]glucose and [U-13C4]3-hydroxybutyrate in rat brain as detected by 13C NMR spectroscopy. NMR Biomed 6:264–277

    Article  PubMed  CAS  Google Scholar 

  • LaNoue KF, Schoolwerth AC (1979) Metabolite transport in mitochondria. Annu Rev Biochem 48:871–922

    Article  PubMed  CAS  Google Scholar 

  • Lapidot A, Gopher A (1994) Cerebral metabolic compartmentation. Estimation of glucose flux via pyruvate carboxylase/pyruvate dehydrogenase by 13C NMR isotopomer analysis of D-[U-13C]glucose metabolites. J Biol Chem 269:27198–27208

    PubMed  CAS  Google Scholar 

  • Laughton JD, Charnay Y, Belloir B, Pellerin L, Magistretti PJ, Bouras C (2000) Differential messenger RNA distribution of lactate dehydrogenase LDH-1 and LDH-5 isoforms in the rat brain. Neuroscience 96:619–625

    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 

  • Leino RL, Gerhart DZ, Drewes LR (1999) Monocarboxylate transporter (MCT1) abundance in brains of suckling and adult rats: a quantitative electron microscopic immunogold study. Brain Res Dev Brain Res 113:47–54

    Article  PubMed  CAS  Google Scholar 

  • Loeber G, Infante AA, Maurer-Fogy I, Krystek E, Dworkin MB (1991) Human NAD+-dependent mitochondrial malic enzyme. cDNA cloning, primary structure, and expression in Escherichia coli. J Biol Chem 266:3016–3021

    PubMed  CAS  Google Scholar 

  • Loffler T, Al-Robaiy S, Bigl M, Eschrich K, Schliebs R (2001) Expression of fructose-1,6-bisphosphatase mRNA isoforms in normal and basal forebrain cholinergic lesioned rat brain. Int J Dev Neurosci 19:279–285

    Article  PubMed  CAS  Google Scholar 

  • Mac M, Nalecz KA (2003) Expression of monocarboxylic acid transporters (MCT) in brain cells. Implication for branched chain alpha-ketoacids transport in neurons. Neurochem Int 43: 305–309

    Article  PubMed  CAS  Google Scholar 

  • Magistretti PJ, Allaman I (2007) Glycogen: a Trojan horse for neurons. Nat Neurosci 10: 1341–1342

    Article  PubMed  CAS  Google Scholar 

  • Magistretti PJ, Pellerin L (1997) Metabolic coupling during activation. A cellular view. Adv Exp Med Biol 413:161–166

    PubMed  CAS  Google Scholar 

  • Magistretti PJ, Pellerin L (1999) Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci 354:1155–1163

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Hernandez A, Bell KP, Noremberg MD (1977) Glutamine synthase: glila localization in brain. Science 195:1356–1358

    Article  PubMed  CAS  Google Scholar 

  • Mason GF, Behar KL, Rothman DL, Shulman RG (1992a) NMR determination of intracerebral glucose concentration and transport kinetics in rat brain. J Cereb Blood Flow Metab 12:448–455

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Mason GF, Gruetter R, Rothman DL, Behar KL, Shulman RG, Novotny EJ (1995) Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. J Cereb Blood Flow Metab 15:12–25

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto K, Yamada K, Kohmura E, Kinoshita ATH (1994) Role of pyruvate in ischemia like conditions on cultured neurons. Neurol Res 16:460–464

    PubMed  CAS  Google Scholar 

  • McKenna MC (2007) The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain. J Neurosci Res 85:3347–3358

    Article  PubMed  CAS  Google Scholar 

  • McKenna MC, Stevenson JH, Huang X, Tildon JT, Zielke CL, Hopkins IB (2000) 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Medina JM, Tabernero A, Tovar JA, Martin-Barrientos J (1996) Metabolic fuel utilization and pyruvate oxidation during the postnatal period. J Inherit Metab Dis 19:432–442

    Article  PubMed  CAS  Google Scholar 

  • Moore SA (2001) Polyunsaturated fatty acid synthesis and release by brain-derived cells in vitro. J Mol Neurosci 16:195–200, discussion 215–121

    Article  PubMed  CAS  Google Scholar 

  • Morris P, Bachelard H (2003) Reflections on the application of 13C-MRS to research on brain metabolism. NMR Biomed 16:303–312

    Article  PubMed  CAS  Google Scholar 

  • Nakai N, Obayashi M, Nagasaki M, Sato Y, Fujitsuka N, Yoshimura A, Miyazaki Y, Sugiyama S, Shimomura Y (2000) The abundance of mRNAs for pyruvate dehydrogenase kinase isoenzymes in brain regions of young and aged rats. Life Sci 68:497–503

    Article  PubMed  CAS  Google Scholar 

  • Nicholls D (2007) Bioenergetics. In: Lajhta A, Gibson G, Dienel G (eds) Brain energetics. integration of molecular and cellular processes, 3rd edn. Springer, New York, pp 3–16

    Google Scholar 

  • Okada Y, Lipton P (2007) Glucose, oxidative energy metabolism, and neural function in brain slices—glycolysis plays a key role in neural activity. In: Lajhta A, Gibson G, Dienel G (eds) Brain energetics. integration of molecular and cellular processes, 3rd edn. Springer, New York, pp 17–39

    Google Scholar 

  • Olstad E, Olsen GM, Qu H, Sonnewald U (2007) Pyruvate recycling in cultured neurons from cerebellum. J Neurosci Res 85:3318–3325

    Article  PubMed  CAS  Google Scholar 

  • Palmieri F (1994) Mitochondrial carrier proteins. FEBS Lett 346:48–54

    Article  PubMed  CAS  Google Scholar 

  • Palmieri F (2004) The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch 447:689–709

    Article  PubMed  CAS  Google Scholar 

  • Palmieri F, Bisaccia F, Capobianco L, Dolce V, Fiermonte G, Iacobazzi V, Indiveri C, Palmieri L (1996) Mitochondrial metabolite transporters. Biochim Biophys Acta 1275:127–132

    Article  PubMed  Google Scholar 

  • Palmieri L, Pardo B, Lasorsa FM, del Arco A, Kobayashi K, Iijima M, Runswick MJ, Walker JE, Saheki T, Satrustegui J et al (2001) Citrin and aralar1 are Ca2+-stimulated aspartate/glutamate transporters in mitochondria. EMBO J 20:5060–5069

    Article  PubMed  CAS  Google Scholar 

  • Pascual JM, Carceller F, Roda JM, Cerdan S, Pascual JM, Carceller F, Roda JM, Cerdan S (1998) Glutamate, glutamine, and GABA as substrates for the neuronal and glial compartments after focal cerebral ischemia in rats. Stroke 29:1048–1056, discussion 1056–1047

    Article  PubMed  CAS  Google Scholar 

  • Passonneau JV, Lowry OH (1964) The role of phosphofructokinase in metabolic regulation. Adv Enzyme Regul 2:265–274

    Article  PubMed  CAS  Google Scholar 

  • Patel MS, Korotchkina LG (2001) Regulation of mammalian pyruvate dehydrogenase complex by phosphorylation: complexity of multiple phosphorylation sites and kinases. Exp Mol Med 33:191–197

    PubMed  CAS  Google Scholar 

  • Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 91:10625–10629

    Article  PubMed  CAS  Google Scholar 

  • Pellerin L, Pellegri G, Bittar PG, Charnay Y, Bouras C, Martin JL, Stella N, Magistretti PJ (1998a) Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Dev Neurosci 20:291–299

    Article  PubMed  CAS  Google Scholar 

  • Pellerin L, Pellegri G, Martin JL, Magistretti PJ (1998b) Expression of monocarboxylate transporter mRNAs in mouse brain: support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain. Proc Natl Acad Sci USA 95:3990–3995

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Rafiki A, Boulland JL, Halestrap AP, Ottersen OP, Bergersen L (2003) Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain. Neuroscience 122:677–688

    Article  PubMed  CAS  Google Scholar 

  • Ramirez BG, Rodrigues TB, Violante IR, Cruz F, Fonseca LL, Ballesteros P, Castro MM, Garcia-Martin ML, Cerdan S (2007) Kinetic properties of the redox switch/redox coupling mechanism as determined in primary cultures of cortical neurons and astrocytes from rat brain. J Neurosci Res 85:3244–3253

    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 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  PubMed  CAS  Google Scholar 

  • Richard J (1963) Lactic dehydrogenase isoenzymes in the nervous system. Actions and relations to hydrosoluble proteins and mineral elements. Ann Soc R Sci Med Nat Brux 16:185–223, CONCL

    PubMed  CAS  Google Scholar 

  • Rodrigues TB, Cerdan S (2005a) 13C MRS: an outstanding tool for metabolic studies. Concepts Magn Reson, Part A 27A:1–16

    Article  CAS  Google Scholar 

  • Rodrigues TB, Cerdan S (2005b) A fast and sensitive 1H NMR method to measure the turnover of the H2 hydrogen of lactate. Magn Reson Med 54:1014–1019

    Article  PubMed  CAS  Google Scholar 

  • Rodrigues TB, Cerdan S (2007) The cerebral tricarboxylic acid cycles. In: Dienel G, Gibson G, Lajtha A (eds) Brain energetics from genes to cells, integration of molecular and cellular processes. Springer, New York, pp 61–93

    Google Scholar 

  • Rodrigues TB, Gray HL, Benito M, Garrido S, Sierra A, Geraldes CF, Ballesteros P, Cerdan S (2005) Futile cycling of lactate through the plasma membrane of C6 glioma cells as detected by (13C, 2H) NMR. J Neurosci Res 79:119–127

    Article  PubMed  CAS  Google Scholar 

  • Rodrigues TB, Granado N, Ortiz O, Cerdan S, Moratalla R (2007) Metabolic interactions between glutamatergic and dopaminergic neurotransmitter systems are mediated through D1 dopamine receptors. J Neurosci Res 85:3284–3293

    Article  PubMed  CAS  Google Scholar 

  • Rodrigues TB, Lopez-Larrubia P, Cerdan S (2009) Redox dependence and compartmentation of [13C]pyruvate in the brain of deuterated rats bearing implanted C6 gliomas. J Neurochem 109(Suppl 1):237–245

    Article  PubMed  CAS  Google Scholar 

  • Ross B, Lin A, Harris K, Bhattacharya P, Schweinsburg B (2003) Clinical experience with 13C MRS in vivo. NMR Biomed 16:358–369

    Article  PubMed  CAS  Google Scholar 

  • Rothman DL, Behar KL, Hyder F, Shulman RG (2003) In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Annu Rev Physiol 65:401–427

    Article  PubMed  CAS  Google Scholar 

  • Ruscak M, Orlicky J, Zubor V, Hager H (1982) Alanine aminotransferase in bovine brain: purification and properties. J Neurochem 39:210–216

    Article  PubMed  CAS  Google Scholar 

  • Sacktor B, Wilson JE, Tiekert CG (1966) Regulation of glycolysis in brain, in situ, during convulsions. J Biol Chem 241:5071–5075

    PubMed  CAS  Google Scholar 

  • Satrustegui J, Pardo B, Del Arco A (2007) Mitochondrial transporters as novel targets for intracellular calcium signaling. Physiol Rev 87:29–67

    Article  PubMed  CAS  Google Scholar 

  • Schmoll D, Fuhrmann E, Gebhardt R, Hamprecht B (1995) Significant amounts of glycogen are synthesized from 3-carbon compounds in astroglial primary cultures from mice with participation of the mitochondrial phosphoenolpyruvate carboxykinase isoenzyme. Eur J Biochem 227:308–315

    Article  PubMed  CAS  Google Scholar 

  • Schousboe A, Sonnewald U, Waagepetersen HS (2003) Differential roles of alanine in GABAergic and glutamatergic neurons. Neurochem Int 43:311–315

    Article  PubMed  CAS  Google Scholar 

  • Schurr A (2002) Lactate, glucose and energy metabolism in the ischemic brain (Review). Int J Mol Med 10:131–136

    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 

  • Shen J, Petersen KF, Behar KL, Brown P, Nixon TW, Mason GF, Petroff OA, Shulman GI, Shulman RG, Rothman DL (1999) Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proc Natl Acad Sci USA 96:8235–8240

    Article  PubMed  CAS  Google Scholar 

  • Shulman RG, Rothman DL, Behar KL, Hyder F (2004) Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci 27:489–495

    Article  PubMed  CAS  Google Scholar 

  • Sibson NR, Dhankhar A, Mason GF, Behar KL, Rothman DL, Shulman RG (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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Sibson NR, Shen J, Mason GF, Rothman DL, Behar KL, Shulman RG (1998b) Functional energy metabolism: in vivo 13C-NMR spectroscopy evidence for coupling of cerebral glucose consumption and glutamatergic neuronalactivity. Dev Neurosci 20:321–330

    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. J Neurochem 76:975–989

    Article  PubMed  CAS  Google Scholar 

  • Sierra A, Lopes da Fonseca L, Ballesteros P, Cerdan S (2004) Quantitative modelling of H3 hydrogen turnover in (2-13C) glutamate and (2-13C) glutamine during (2-13C) acetate metabolism in the adult rat brain. Proceedings of the XXI Annual Meeting of the European Society for Magnetic Resonance in Medicine and Biology. Copenhagen, p 36

    Google Scholar 

  • Siesjo BK (1982) Lactic acidosis in the brain: occurrence, triggering mechanisms and pathophysiological importance. Ciba Found Symp 87:77–100

    PubMed  CAS  Google Scholar 

  • Sokoloff L (1989) Circulation and energy metabolism of the brain. In: Siegel G, Agranoff B, Albers RW, Molinoff P (eds) Basic neurochemistry. Raven, New York, pp 565–590

    Google Scholar 

  • Sokoloff L (1992) The brain as a chemical machine. Prog Brain Res 94:19–33

    Article  PubMed  CAS  Google Scholar 

  • Sonnewald U, Schousboe A, Qu H, Waagepetersen HS (2004) Intracellular metabolic compartmentation assessed by 13C magnetic resonance spectroscopy. Neurochem Int 45:305–310

    Article  PubMed  CAS  Google Scholar 

  • Takenaka M, Noguchi T, Inoue H, Yamada K, Matsuda T, Tanaka T (1989) Rat pyruvate kinase M gene. Its complete structure and characterization of the 5′-flanking region. J Biol Chem 264:2363–2367

    PubMed  CAS  Google Scholar 

  • Tsacopoulos M, Magistretti PJ (1996) Metabolic coupling between glia and neurons. J Neurosci 16:877–885

    PubMed  CAS  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

    PubMed  Google Scholar 

  • Vannucci SJ, Simpson IA (2003) Developmental switch in brain nutrient transporter expression in the rat. Am J Physiol Endocrinol Metab 285:E1127–E1134

    PubMed  CAS  Google Scholar 

  • Vannucci SJ, Maher F, Simpson IA (1997) Glucose transporter proteins in brain: delivery of glucose to neurons and glia. Glia 21:2–21

    Article  PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  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  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 

  • Westergaard N, Varming T, Peng L, Sonnewald U, Hertz L, Schousboe A (1993) Uptake, release, and metabolism of alanine in neurons and astrocytes in primary cultures. J Neurosci Res 35:540–545

    Article  PubMed  CAS  Google Scholar 

  • Wienhard K (2002) Measurement of glucose consumption using [18F]fluorodeoxyglucose. Methods 27:218–225

    Article  PubMed  CAS  Google Scholar 

  • Yamada K, Noguchi T (1999a) Nutrient and hormonal regulation of pyruvate kinase gene expression. Biochem J 337(Pt 1):1–11

    Article  PubMed  CAS  Google Scholar 

  • Yamada K, Noguchi T (1999b) Regulation of pyruvate kinase M gene expression. Biochem Biophys Res Commun 256:257–262

    Article  PubMed  CAS  Google Scholar 

  • Yang Z, Floyd DL, Loeber G, Tong L (2000) Structure of a closed form of human malic enzyme and implications for catalytic mechanism. Nat Struct Biol 7:251–257

    Article  PubMed  CAS  Google Scholar 

  • Zwingmann C, Leibfritz D (2003) Regulation of glial metabolism studied by 13C-NMR. NMR Biomed 16:370–399

    Article  PubMed  CAS  Google Scholar 

  • Zwingmann C, Richter-Landsberg C, Brand A, Leibfritz D (2000) NMR spectroscopic study on the metabolic fate of [3-13C]alanine in astrocytes, neurons, and cocultures: implications for glia-neuron interactions in neurotransmitter metabolism. Glia 32:286–303

    Article  PubMed  CAS  Google Scholar 

  • Zwingmann C, Richter-Landsberg C, Leibfritz D (2001) 13C isotopomer analysis of glucose and alanine metabolism reveals cytosolic pyruvate compartmentation as part of energy metabolism in astrocytes. Glia 34:200–212

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants SAF 2001–2245, SAF 2004–03197, SAF 2008–01397 and S-BIO/0179/2006 to S.C and P.B. T.B.R. was a fellow from FCT-Portugal (SFRH/BPD/26881/2006). A.S. was a predoctoral fellow from UNED. Authors are indebted to Mr. Javier Pérez for the final drafting of the illustrations.

Author information

Authors and Affiliations

  1. Laboratory for Imaging and Spectroscopy by Magnetic Resonance (LISMAR), Institute of Biomedical Research “Alberto Sols“ CSIC/UAM, Madrid, Spainc

    Tiago B. Rodrigues Ph.D.

  2. Laboratory for Imaging and Spectroscopy by Magnetic Resonance (LISMAR), Institute of Biomedical Research “Alberto Sols” CSIC/UAM, Calle Arturo Duperier 4, E-28029, Madrid, Spain

    Alejandra Sierra & Sebastián Cerdán Ph.D.

  3. Laboratory of Organic Synthesis and Molecular Imaging, University at a Distance UNED, Paseo Senda del Rey 9, E-28040, Madrid, Spain

    Paloma Ballesteros Ph.D.

Authors
  1. Tiago B. Rodrigues Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alejandra Sierra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paloma Ballesteros Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sebastián Cerdán Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sebastián Cerdán Ph.D. .

Editor information

Editors and Affiliations

  1. School of Medicine, Hoglund Brain Imaging Center, University of Kansas, Rainbow Blvd. 3901, Kansas City, 66160, Kansas, USA

    In-Young Choi

  2. Inst. Physique de la Matière Complexe, Labo. d'Imagerie Fonctionnelle et, Ecole Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland

    Rolf Gruetter

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Rodrigues, T.B., Sierra, A., Ballesteros, P., Cerdán, S. (2012). Pyruvate Transport and Metabolism in the Central Nervous System. In: Choi, IY., Gruetter, R. (eds) Neural Metabolism In Vivo. Advances in Neurobiology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1788-0_24

Download citation

Publish with us

Policies and ethics

Search

Navigation