Skip to main content

Advertisement

SpringerLink
Log in

Hypothesis: A Novel Neuroprotective Role for Glucose-6-phosphatase (G6PC3) in Brain—To Maintain Energy-Dependent Functions Including Cognitive Processes

  • Review
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The isoform of glucose-6-phosphatase in liver, G6PC1, has a major role in whole-body glucose homeostasis, whereas G6PC3 is widely distributed among organs but has poorly-understood functions. A recent, elegant analysis of neutrophil dysfunction in G6PC3-deficient patients revealed G6PC3 is a neutrophil metabolite repair enzyme that hydrolyzes 1,5-anhydroglucitol-6-phosphate, a toxic metabolite derived from a glucose analog present in food. These patients exhibit a spectrum of phenotypic characteristics and some have learning disabilities, revealing a potential linkage between cognitive processes and G6PC3 activity. Previously-debated and discounted functions for brain G6PC3 include causing an ATP-consuming futile cycle that interferes with metabolic brain imaging assays and a nutritional role involving astrocyte-neuron glucose-lactate trafficking. Detailed analysis of the anhydroglucitol literature reveals that it competes with glucose for transport into brain, is present in human cerebrospinal fluid, and is phosphorylated by hexokinase. Anhydroglucitol-6-phosphate is present in rodent brain and other organs where its accumulation can inhibit hexokinase by competition with ATP. Calculated hexokinase inhibition indicates that energetics of brain and erythrocytes would be more adversely affected by anhydroglucitol-6-phosphate accumulation than heart. These findings strongly support the paradigm-shifting hypothesis that brain G6PC3 removes a toxic metabolite, thereby maintaining brain glucose metabolism- and ATP-dependent functions, including cognitive processes.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

AG:

1,5-Anhydroglucitol

AG6P:

1,5-Anhydroglucitol-6-phosphate

AF:

1,5-Anhydrofructose

BBB:

Blood–brain barrier

CMRglc :

Cerebral metabolic rate for glucose

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DG:

2-Deoxy-d-glucose

DH:

Dehydrogenase

ER:

Endoplasmic reticulum

FDG:

2-Fluoro-2-deoxy-d-glucose

Glc:

Glucose

Glc-6-P:

Glucose-6-phosphate

Glc-1,6-P2 :

Glucose-1,6-bisphosphate

G6Pase:

Glucose-6-phosphatase

G6PC1:

G6Pase isoform predominant in glucogenic organs, liver, kidney, and intestine

G6PC3:

Ubiquitous G6Pase isoform present in low levels in many tissues

G6PT:

Microsomal Glc-6-P transporter

GLUT:

Plasma membrane glucose transporter

HK:

Hexokinase

iv:

Intravenous

Pi:

Inorganic phosphate

PPi:

Pyrophosphate

STZ:

Streptozotocin

References

  1. Hers HG, De Duve C (1950) The hexosephosphatase system; partition of activity of glucose-6-phosphatase in the tissues. Bull Soc Chim Biol (Paris) 32:20–29

    CAS  Google Scholar 

  2. Nordlie RC, Foster JD (2010) A retrospective review of the roles of multifunctional glucose-6-phosphatase in blood glucose homeostasis: Genesis of the tuning/retuning hypothesis. Life Sci 87:339–349

    CAS  PubMed  PubMed Central  Google Scholar 

  3. van Schaftingen E, Gerin I (2002) The glucose-6-phosphatase system. Biochem J 362:513–532

    PubMed  PubMed Central  Google Scholar 

  4. Marcolongo P, Fulceri R, Gamberucci A, Czegle I, Banhegyi G, Benedetti A (2013) Multiple roles of glucose-6-phosphatases in pathophysiology: state of the art and future trends. Biochim Biophys Acta 1830:2608–2618

    CAS  PubMed  Google Scholar 

  5. 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

    CAS  PubMed  Google Scholar 

  6. Forsyth RJ, Bartlett K, Burchell A, Scott HM, Eyre JA (1993) Astrocytic glucose-6-phosphatase and the permeability of brain microsomes to glucose 6-phosphate. Biochem J 294(Pt 1):145–151

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Schousboe A (ed) (2019) Brain glycogen metabolism. Springer, Cham

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  9. Dienel GA (2019) Brain glucose metabolism: integration of energetics with function. Physiol Rev 99:949–1045

    CAS  PubMed  Google Scholar 

  10. Dienel GA, Rothman DL (2019) Glycogenolysis in cerebral cortex during sensory stimulation, acute hypoglycemia, and exercise: Impact on astrocytic energetics, aerobic glycolysis, and astrocyte-neuron interactions. Adv Neurobiol 23:209–267

    PubMed  Google Scholar 

  11. Dienel GA (2019) Does shuttling of glycogen-derived lactate from astrocytes to neurons take place during neurotransmission and memory consolidation? J Neurosci Res 97:863–882

    CAS  PubMed  Google Scholar 

  12. Martin CC, Oeser JK, Svitek CA, Hunter SI, Hutton JC, O'Brien RM (2002) Identification and characterization of a human cDNA and gene encoding a ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein. J Mol Endocrinol 29:205–222

    CAS  PubMed  Google Scholar 

  13. Guionie O, Clottes E, Stafford K, Burchell A (2003) Identification and characterisation of a new human glucose-6-phosphatase isoform. FEBS Lett 551:159–164

    CAS  PubMed  Google Scholar 

  14. Boustead JN, Martin CC, Oeser JK, Svitek CA, Hunter SI, Hutton JC, O'Brien RM (2004) Identification and characterization of a cDNA and the gene encoding the mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein. J Mol Endocrinol 32:33–53

    CAS  PubMed  Google Scholar 

  15. Shieh JJ, Pan CJ, Mansfield BC, Chou JY (2004) A potential new role for muscle in blood glucose homeostasis. J Biol Chem 279:26215–26219

    CAS  PubMed  Google Scholar 

  16. Shieh JJ, Pan CJ, Mansfield BC, Chou JY (2003) A glucose-6-phosphate hydrolase, widely expressed outside the liver, can explain age-dependent resolution of hypoglycemia in glycogen storage disease type Ia. J Biol Chem 278:47098–47103

    CAS  PubMed  Google Scholar 

  17. Ghosh A, Cheung YY, Mansfield BC, Chou JY (2005) Brain contains a functional glucose-6-phosphatase complex capable of endogenous glucose production. J Biol Chem 280:11114–11119

    CAS  PubMed  Google Scholar 

  18. Veiga-da-Cunha M, Chevalier N, Stephenne X, Defour JP, Paczia N, Ferster A, Achouri Y, Dewulf JP, Linster CL, Bommer GT, Van Schaftingen E (2019) Failure to eliminate a phosphorylated glucose analog leads to neutropenia in patients with G6PT and G6PC3 deficiency. Proc Natl Acad Sci USA 116:1241–1250

    CAS  PubMed  Google Scholar 

  19. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916

    CAS  PubMed  Google Scholar 

  20. Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Hoffman E, Alavi A, Som P, Sokoloff L (1979) The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 44:127–137

    CAS  PubMed  Google Scholar 

  21. Sokoloff L (1981) Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J Cereb Blood Flow Metab 1:7–36

    CAS  PubMed  Google Scholar 

  22. Nelson T, Lucignani G, Goochee J, Crane AM, Sokoloff L (1986) Invalidity of criticisms of the deoxyglucose method based on alleged glucose-6-phosphatase activity in brain. J Neurochem 46:905–919

    CAS  PubMed  Google Scholar 

  23. Huang M, Veech RL (1982) The quantitative determination of the in vivo dephosphorylation of glucose 6-phosphate in rat brain. J Biol Chem 257:11358–11363

    CAS  PubMed  Google Scholar 

  24. Huang MT, Veech RL (1986) Glucose-6-phosphatase activity in brain. Science 234:1128–1129

    CAS  PubMed  Google Scholar 

  25. Nelson T, Lucignani G, Atlas S, Crane AM, Dienel GA, Sokoloff L (1985) Reexamination of glucose-6-phosphatase activity in the brain in vivo: no evidence for a futile cycle. Science 229:60–62

    CAS  PubMed  Google Scholar 

  26. Dienel GA, Nelson T, Cruz NF, Jay T, Crane AM, Sokoloff L (1988) Over-estimation of glucose-6-phosphatase activity in brain in vivo. Apparent difference in rates of [2-3H]glucose and [U-14C]glucose utilization is due to contamination of precursor pool with 14C-labeled products and incomplete recovery of 14C-labeled metabolites. J Biol Chem 263:19697–19708

    CAS  PubMed  Google Scholar 

  27. Huang MT, Veech RL (1985) Metabolic fluxes between [14C]2-deoxy-D-glucose and [14C]2-deoxy-D-glucose-6-phosphate in brain in vivo. J Neurochem 44:567–573

    CAS  PubMed  Google Scholar 

  28. Hawkins RA, Miller AL (1978) Loss of radioactive 2-deoxy-D-glucose-6-phosphate from brains of conscious rats: implications for quantitative autoradiographic determination of regional glucose utilization. Neuroscience 3:251–258

    CAS  PubMed  Google Scholar 

  29. Dienel GA, Cruz NF, Mori K, Sokoloff L (1990) Acid lability of metabolites of 2-deoxyglucose in rat brain: implications for estimates of kinetic parameters of deoxyglucose phosphorylation and transport between blood and brain. J Neurochem 54:1440–1448

    CAS  PubMed  Google Scholar 

  30. Dienel GA, Cruz NF (1993) Synthesis of deoxyglucose-1-phosphate, deoxyglucose-1,6-bisphosphate, and other metabolites of 2-deoxy-D-[14C]glucose in rat brain in vivo: influence of time and tissue glucose level. J Neurochem 60:2217–2231

    CAS  PubMed  Google Scholar 

  31. Dienel GA, Cruz NF, Sokoloff L (1993) Metabolites of 2-deoxy-[14C]glucose in plasma and brain: influence on rate of glucose utilization determined with deoxyglucose method in rat brain. J Cereb Blood Flow Metab 13:315–327

    CAS  PubMed  Google Scholar 

  32. Müller MS, Fouyssac M, Taylor CW (2018) Effective glucose uptake by human astrocytes requires its sequestration in the endoplasmic reticulum by glucose-6-phosphatase-beta. Curr Biol 28(3481–3486):e3484

    Google Scholar 

  33. Dienel GA (2019) The "protected" glucose transport through the astrocytic endoplasmic reticulum is too slow to serve as a quantitatively-important highway for nutrient delivery. J Neurosci Res 97:854–862

    CAS  PubMed  Google Scholar 

  34. Wortmann SB, Van Hove JLK, Derks TGJ, Chevalier N, Knight V, Koller A, Oussuren E, Mayr JA, van Spronsen FJ, Lagler FB, Gaughan S, Van Schaftingen E, Veiga-da-Cunha M (2020) Treating neutropenia and neutrophil dysfunction in glycogen storage disease IB with an SGLT2-inhibitor. Blood. https://doi.org/10.1182/blood.2019004465

    Article  PubMed  PubMed Central  Google Scholar 

  35. Veiga-da-Cunha M, Van Schaftingen E, Bommer GT (2020) Inborn errors of metabolite repair. J Inherit Metab Dis 43:14–24

    CAS  PubMed  Google Scholar 

  36. Van Schaftingen E, Rzem R, Marbaix A, Collard F, Veiga-da-Cunha M, Linster CL (2013) Metabolite proofreading, a neglected aspect of intermediary metabolism. J Inherit Metab Dis 36:427–434

    CAS  PubMed  Google Scholar 

  37. Bommer GT, Van Schaftingen E, Veiga-da-Cunha M (2020) Metabolite repair enzymes control metabolic damage in glycolysis. Trends Biochem Sci 45:228–243

    CAS  PubMed  Google Scholar 

  38. Lin SR, Pan CJ, Mansfield BC, Chou JY (2015) Functional analysis of mutations in a severe congenital neutropenia syndrome caused by glucose-6-phosphatase-beta deficiency. Mol Genet Metab 114:41–45

    CAS  PubMed  Google Scholar 

  39. Banka S (2015) G6PC3 deficiency. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A (eds) GeneReviews((R)). University of Washington, Seattle, pp 1–16

    Google Scholar 

  40. Banka S, Newman WG (2013) A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations. Orphanet J Rare Dis 8:84

    PubMed  PubMed Central  Google Scholar 

  41. Boztug K, Rosenberg PS, Dorda M, Banka S, Moulton T, Curtin J, Rezaei N, Corns J, Innis JW, Avci Z, Tran HC, Pellier I, Pierani P, Fruge R, Parvaneh N, Mamishi S, Mody R, Darbyshire P, Motwani J, Murray J, Buchanan GR, Newman WG, Alter BP, Boxer LA, Donadieu J, Welte K, Klein C (2012) Extended spectrum of human glucose-6-phosphatase catalytic subunit 3 deficiency: novel genotypes and phenotypic variability in severe congenital neutropenia. J Pediatr 160:679–683.e672

    CAS  PubMed  Google Scholar 

  42. Banka S, Chervinsky E, Newman WG, Crow YJ, Yeganeh S, Yacobovich J, Donnai D, Shalev S (2011) Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3. Eur J Hum Genet 19:18–22

    PubMed  Google Scholar 

  43. Desplantes C, Fremond ML, Beaupain B, Harousseau JL, Buzyn A, Pellier I, Roques G, Morville P, Paillard C, Bruneau J, Pinson L, Jeziorski E, Vannier JP, Picard C, Bellanger F, Romero N, de Pontual L, Lapillonne H, Lutz P, Chantelot CB, Donadieu J (2014) Clinical spectrum and long-term follow-up of 14 cases with G6PC3 mutations from the French severe congenital neutropenia registry. Orphanet J Rare Dis 9:183

    PubMed  PubMed Central  Google Scholar 

  44. Aróstegui JI, de Toledo JS, Pascal M, García C, Yagüe J, Díaz de Heredia C (2009) A novel G6PC3 homozygous 1-bp deletion as a cause of severe congenital neutropenia. Blood 114:1718–1719

    PubMed  Google Scholar 

  45. Aytekin C, Germeshausen M, Tuygun N, Dogu F, Ikinciogullari A (2013) A novel G6PC3 gene mutation in a patient with severe congenital neutropenia. J Pediatr Hematol Oncol 35:e81–83

    PubMed  Google Scholar 

  46. Lebel A, Yacobovich J, Krasnov T, Koren A, Levin C, Kaplinsky C, Ravel-Vilk S, Laor R, Attias D, Barak AB, Shtager D, Stein J, Kuperman A, Miskin H, Dgany O, Giri N, Alter BP, Tamary H (2015) Genetic analysis and clinical picture of severe congenital neutropenia in Israel. Pediatr Blood Cancer 62:103–108

    CAS  PubMed  Google Scholar 

  47. Kiykim A, Baris S, Karakoc-Aydiner E, Ozen AO, Ogulur I, Bozkurt S, Ataizi CC, Boztug K, Barlan IB (2015) G6PC3 deficiency: primary immune deficiency beyond just neutropenia. J Pediatr Hematol Oncol 37:616–622

    CAS  PubMed  Google Scholar 

  48. Cheung YY, Kim SY, Yiu WH, Pan CJ, Jun HS, Ruef RA, Lee EJ, Westphal H, Mansfield BC, Chou JY (2007) Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta. J Clin Invest 117:784–793

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Wang Y, Oeser JK, Yang C, Sarkar S, Hackl SI, Hasty AH, McGuinness OP, Paradee W, Hutton JC, Powell DR, O'Brien RM (2006) Deletion of the gene encoding the ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein (UGRP)/glucose-6-phosphatase catalytic subunit-beta results in lowered plasma cholesterol and elevated glucagon. J Biol Chem 281:39982–39989

    CAS  PubMed  Google Scholar 

  50. Sokoloff L (1960) Metabolism of the central nervous system in vivo. In: Field J, Magoun HW, Hall VE (eds) Handbook of physiology—neurophysiology. American Physiological Society, Washington, DC, pp 1843–1864

    Google Scholar 

  51. Sols A, Crane RK (1954) Substrate specificity of brain hexokinase. J Biol Chem 210:581–595

    CAS  PubMed  Google Scholar 

  52. Crane RK, Sols A (1954) The non-competitive inhibition of brain hexokinase by glucose-6-phosphate and related compounds. J Biol Chem 210:597–606

    CAS  PubMed  Google Scholar 

  53. Betz AL, Drewes LR, Gilboe DD (1975) Inhibition of glucose transport into brain by phlorizin, phloretin and glucose analogues. Biochim Biophys Acta 406:505–515

    CAS  PubMed  Google Scholar 

  54. Pitkänen E (1973) Occurrence of 1,5-anhydroglucitol in human cerebrospinal fluid. Clin Chim Acta 48:159–166

    PubMed  Google Scholar 

  55. Krhac M, Lovrencic MV (2019) Update on biomarkers of glycemic control. World J Diabetes 10:1–15

    PubMed  PubMed Central  Google Scholar 

  56. Wilson TH, Crane RK (1958) The specificity of sugar transport by hamster intestine. Biochim Biophys Acta 29:30–32

    CAS  PubMed  Google Scholar 

  57. Crane RK (1960) Intestinal absorption of sugars. Physiol Rev 40:789–825

    CAS  PubMed  Google Scholar 

  58. Crane RK (1960) Studies on the mechanism of the intestinal absorption of sugars. III. Mutual inhibition, in vitro, between some actively transported sugars. Biochim Biophys Acta 45:477–482

    CAS  PubMed  Google Scholar 

  59. Crane RK, Mandelstam P (1960) The active transport of sugars by various preparations of hamster intestine. Biochim Biophys Acta 45:460–476

    CAS  PubMed  Google Scholar 

  60. Stickle D, Turk J (1997) A kinetic mass balance model for 1,5-anhydroglucitol: applications to monitoring of glycemic control. Am J Physiol 273:E821–830

    CAS  PubMed  Google Scholar 

  61. Nerby CL, Stickle DF (2009) 1,5-anhydroglucitol monitoring in diabetes: a mass balance perspective. Clin Biochem 42:158–167

    CAS  PubMed  Google Scholar 

  62. McGill JB, Cole TG, Nowatzke W, Houghton S, Ammirati EB, Gautille T, Sarno MJ (2004) Circulating 1,5-anhydroglucitol levels in adult patients with diabetes reflect longitudinal changes of glycemia: a U.S. trial of the GlycoMark assay. Diabetes Care 27:1859–1865

    CAS  PubMed  Google Scholar 

  63. Welter M, Boritza KC, Anghebem-Oliveira MI, Henneberg R, Hauser AB, Rego FGM, Picheth G (2018) Data for serum 1,5 anhydroglucitol concentration in different populations. Data Brief 20:753–760

    PubMed  PubMed Central  Google Scholar 

  64. Yamanouchi T, Tachibana Y, Akanuma H, Minoda S, Shinohara T, Moromizato H, Miyashita H, Akaoka I (1992) Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body. Am J Physiol 263:E268–E273

    CAS  PubMed  Google Scholar 

  65. Yu S (2008) The anhydrofructose pathway of glycogen catabolism. IUBMB Life 60:798–809

    CAS  PubMed  Google Scholar 

  66. Fiskesund R, Abeyama K, Yoshinaga K, Abe J, Yuan Y, Yu S (2010) 1,5-anhydro-D-fructose and its derivatives: biosynthesis, preparation and potential medical applications. Planta Med 76:1635–1641

    CAS  PubMed  Google Scholar 

  67. Rozeboom HJ, Yu S, Madrid S, Kalk KH, Zhang R, Dijkstra BW (2013) Crystal structure of alpha-1,4-glucan lyase, a unique glycoside hydrolase family member with a novel catalytic mechanism. J Biol Chem 288:26764–26774

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Yip VL, Withers SG (2006) Breakdown of oligosaccharides by the process of elimination. Curr Opin Chem Biol 10:147–155

    CAS  PubMed  Google Scholar 

  69. Okuyama M, Saburi W, Mori H, Kimura A (2016) α-Glucosidases and α-1,4-glucan lyases: structures, functions, and physiological actions. Cell Mol Life Sci 73:2727–2751

    CAS  PubMed  Google Scholar 

  70. Suzuki M, Mizuno H, Akanuma Y, Akanuma H (1994) Synthesis of 1, 5-anhydro-D-glucitol from glucose in rat hepatoma cells. J Biochem 115:87–92

    CAS  PubMed  Google Scholar 

  71. Suzuki M, Kametani S, Uchida K, Akanuma H (1996) Production of 1,5-anhydroglucitol from 1,5-anhydrofructose in erythroleukemia cells. Eur J Biochem 240:23–29

    CAS  PubMed  Google Scholar 

  72. Kametani S, Shiga Y, Akanuma H (1996) Hepatic Production of 1,5-anhydrofructose and 1,5-anhydroglucitol in rat by the third glycogenolytic pathway. Eur J Biochem 242:832–838

    CAS  PubMed  Google Scholar 

  73. Sakuma M, Kametani S, Akanuma H (1998) Purification and some properties of a hepatic NADPH-dependent reductase that specifically acts on 1, 5-anhydro-D-fructose. J Biochem 123:189–193

    CAS  PubMed  Google Scholar 

  74. Sakasai-Sakai A, Takata T, Suzuki H, Maruyama I, Motomiya Y, Takeuchi M (2019) Immunological evidence for in vivo production of novel advanced glycation end-products from 1,5-anhydro-D-fructose, a glycogen metabolite. Sci Rep 9:10194

    PubMed  PubMed Central  Google Scholar 

  75. Hirano K, Ziak M, Kamoshita K, Sukenaga Y, Kametani S, Shiga Y, Roth J, Akanuma H (2000) N-linked oligosaccharide processing enzyme glucosidase II produces 1,5-anhydrofructose as a side product. Glycobiology 10:1283–1289

    CAS  PubMed  Google Scholar 

  76. Kornfeld R, Kornfeld S (1985) Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem 54:631–664

    CAS  PubMed  Google Scholar 

  77. Anji A, Miller H, Raman C, Phillips M, Ciment G, Kumari M (2015) Expression of alpha-subunit of alpha-glucosidase II in adult mouse brain regions and selected organs. J Neurosci Res 93:82–93

    CAS  PubMed  Google Scholar 

  78. Byman E, Schultz N, Fex M, Wennstrom M (2018) Brain alpha-amylase: a novel energy regulator important in Alzheimer disease? Brain Pathol 28:920–932

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Byman E, Schultz N, Blom AM, Wennstrom M (2019) A potential role for alpha-amylase in amyloid-beta-induced astrocytic glycogenolysis and activation. J Alzheimers Dis 68:205

    CAS  PubMed  Google Scholar 

  80. Crane RK, Field RA, Cori CF (1957) Studies of tissue permeability. I. The penetration of sugars into the Ehrlich ascites tumor cells. J Biol Chem 224:649–662

    CAS  PubMed  Google Scholar 

  81. Imle R, Wang BT, Stutzenberger N, Birkenhagen J, Tandon A, Carl M, Himmelreich N, Thiel C, Grone HJ, Poschet G, Volkers M, Gulow K, Schroder A, Carillo S, Mittermayr S, Bones J, Kaminski MM, Kolker S, Sauer SW (2019) ADP-dependent glucokinase regulates energy metabolism via ER-localized glucose sensing. Sci Rep 9:14248

    PubMed  Google Scholar 

  82. Kaminski MM, Sauer SW, Kaminski M, Opp S, Ruppert T, Grigaravicius P, Grudnik P, Grone HJ, Krammer PH, Gulow K (2012) T cell activation is driven by an ADP-dependent glucokinase linking enhanced glycolysis with mitochondrial reactive oxygen species generation. Cell Rep 2:1300–1315

    CAS  PubMed  Google Scholar 

  83. Richter JP, Goroncy AK, Ronimus RS, Sutherland-Smith AJ (2016) The structural and functional characterization of mammalian ADP-dependent glucokinase. J Biol Chem 291:3694–3704

    CAS  PubMed  Google Scholar 

  84. Richter S, Richter JP, Mehta SY, Gribble AM, Sutherland-Smith AJ, Stowell KM, Print CG, Ronimus RS, Wilson WR (2012) Expression and role in glycolysis of human ADP-dependent glucokinase. Mol Cell Biochem 364:131–145

    CAS  PubMed  Google Scholar 

  85. Weil-Malherbe H, Bone AD (1951) Studies on hexokinase. 1. The hexokinase activity of rat-brain extracts. Biochem J 49:339–347

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Crane RK, Sols A (1953) The association of hexokinase with particulate fractions of brain and other tissue homogenates. J Biol Chem 203:273–292

    CAS  PubMed  Google Scholar 

  87. Wilson JE, Chung V (1989) Rat brain hexokinase: further studies on the specificity of the hexose and hexose 6-phosphate binding sites. Arch Biochem Biophys 269:517–525

    CAS  PubMed  Google Scholar 

  88. Rose IA, Warms JV, Kosow DP (1974) Specificity for the glucose-6-P inhibition site of hexokinase. Arch Biochem Biophys 164:729–735

    CAS  PubMed  Google Scholar 

  89. Grossbard L, Schimke RT (1966) Multiple hexokinases of rat tissues. Purification and comparison of soluble forms. J Biol Chem 241:3546–3560

    CAS  PubMed  Google Scholar 

  90. Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 206:2049–2057

    CAS  PubMed  Google Scholar 

  91. Hashimoto M, Wilson JE (2000) Membrane potential-dependent conformational changes in mitochondrially bound hexokinase of brain. Arch Biochem Biophys 384:163–173

    CAS  PubMed  Google Scholar 

  92. Crane RK (1955) The substrate specificity of liver glucose-6-phosphatase. Biochim Biophys Acta 17:443–444

    CAS  PubMed  Google Scholar 

  93. Ferrari RA, Mandelstam P, Crane RK (1959) 1,5-Anhydro-d-glucitol 6-phosphate and its use for the specific inhibition of the hexokinase reaction in tissue homogenates. Arch Biochem Biophys 80:372–377

    CAS  Google Scholar 

  94. Clarke JL, Mason PJ (2003) Murine hexose-6-phosphate dehydrogenase: a bifunctional enzyme with broad substrate specificity and 6-phosphogluconolactonase activity. Arch Biochem Biophys 415:229–234

    CAS  PubMed  Google Scholar 

  95. Bánhegyi G, Csala M, Benedetti A (2009) Hexose-6-phosphate dehydrogenase: linking endocrinology and metabolism in the endoplasmic reticulum. J Mol Endocrinol 42:283–289

    PubMed  Google Scholar 

  96. Kardon T, Senesi S, Marcolongo P, Legeza B, Banhegyi G, Mandl J, Fulceri R, Benedetti A (2008) Maintenance of luminal NADPH in the endoplasmic reticulum promotes the survival of human neutrophil granulocytes. FEBS Lett 582:1809–1815

    CAS  PubMed  Google Scholar 

  97. Gerin I, Van Schaftingen E (2002) Evidence for glucose-6-phosphate transport in rat liver microsomes. FEBS Lett 517:257–260

    CAS  PubMed  Google Scholar 

  98. Jun HS, Cheung YY, Lee YM, Mansfield BC, Chou JY (2012) Glucose-6-phosphatase-beta, implicated in a congenital neutropenia syndrome, is essential for macrophage energy homeostasis and functionality. Blood 119:4047–4055

    CAS  PubMed  Google Scholar 

  99. Jun HS, Lee YM, Cheung YY, McDermott DH, Murphy PM, De Ravin SS, Mansfield BC, Chou JY (2010) Lack of glucose recycling between endoplasmic reticulum and cytoplasm underlies cellular dysfunction in glucose-6-phosphatase-beta-deficient neutrophils in a congenital neutropenia syndrome. Blood 116:2783–2792

    CAS  PubMed  Google Scholar 

  100. Valentine WN, Tanaka KR, Paglia DE (1985) Hemolytic anemias and erythrocyte enzymopathies. Ann Intern Med 103:245–257

    CAS  PubMed  Google Scholar 

  101. Bertero E, Maack C (2018) Metabolic remodelling in heart failure. Nat Rev Cardiol 15:457–470

    CAS  PubMed  Google Scholar 

  102. Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85:1093–1129

    CAS  PubMed  Google Scholar 

  103. Nehlig A, Pereira de Vasconcelos A (1993) Glucose and ketone body utilization by the brain of neonatal rats. Prog Neurobiol 40:163–221

    CAS  PubMed  Google Scholar 

  104. Barnett JE, Holman GD, Munday KA (1973) Structural requirements for binding to the sugar-transport system of the human erythrocyte. Biochem J 131:211–221

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Kahlenberg A, Dolansky D (1972) Structural requirements of D-glucose for its binding to isolated human erythrocyte membranes. Can J Biochem 50:638–643

    CAS  PubMed  Google Scholar 

  106. Simpson IA, Carruthers A, Vannucci SJ (2007) Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab 27:1766–1791

    CAS  PubMed  Google Scholar 

  107. Augustin R (2010) The protein family of glucose transport facilitators: it's not only about glucose after all. IUBMB Life 62:315–333

    CAS  PubMed  Google Scholar 

  108. Simpson IA, Dwyer D, Malide D, Moley KH, Travis A, Vannucci SJ (2008) The facilitative glucose transporter GLUT3: 20 years of distinction. Am J Physiol Endocrinol Metab 295:E242–253

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Rumsey SC, Kwon O, Xu GW, Burant CF, Simpson I, Levine M (1997) Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J Biol Chem 272:18982–18989

    CAS  PubMed  Google Scholar 

  110. Maher F, Davies-Hill TM, Simpson IA (1996) Substrate specificity and kinetic parameters of GLUT3 in rat cerebellar granule neurons. Biochem J 315(Pt 3):827–831

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Okuno Y, Nishizawa Y, Kawagishi T, Sekiya K, Shoji T, Morii H (1992) Transport of 1, 5-anhydro-D-glucitol into human polymorphonuclear leukocytes. J Biochem 111:99–102

    CAS  PubMed  Google Scholar 

  112. Schuster DP, Brody SL, Zhou Z, Bernstein M, Arch R, Link D, Mueckler M (2007) Regulation of lipopolysaccharide-induced increases in neutrophil glucose uptake. Am J Physiol-Lung Cell Mol Physiol 292:L845–L851

    CAS  PubMed  Google Scholar 

  113. Wilson JE (1985) Regulation of mammalian hexokinase activity. In: Beitner R (ed) Regul carbohydrate metab. CRC Press Inc, Boca Raton, FL, pp 45–85

    Google Scholar 

  114. Wilkin GP, Wilson JE (1977) Localization of hexokinase in neural tissue: light microscopic studies with immunofluorescence and histochemical procedures. J Neurochem 29:1039–1051

    CAS  PubMed  Google Scholar 

  115. Kao-Jen J, Wilson JE (1980) Localization of hexokinase in neural tissue: electron microscopic studies of rat cerebellar cortex. J Neurochem 35:667–678

    CAS  PubMed  Google Scholar 

  116. Yu Y, Herman P, Rothman DL, Agarwal D, Hyder F (2018) Evaluating the gray and white matter energy budgets of human brain function. J Cereb Blood Flow Metab 38:0339–1353

    Google Scholar 

  117. Patel AB, Lai JC, Chowdhury GM, Hyder F, Rothman DL, Shulman RG, Behar KL (2014) Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle. Proc Natl Acad Sci USA 111:5385–5390

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Cataldo AM, Broadwell RD (1986) Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions: I. Neurons and glia. J Electron Microsc Tech 3:413–437

    CAS  Google Scholar 

  119. Stephens HR, Sandborn EB (1976) Cytochemical localization of glucose-6-phosphatase activity in the central nervous system of the rat. Brain Res 113:127–146

    CAS  PubMed  Google Scholar 

  120. Al-Ali SY, Robinson N (1981) Ultrastructural demonstration of glucose 6-phosphatase in cerebral cortex. Histochemistry 72:107–111

    CAS  PubMed  Google Scholar 

  121. Duran J, Gruart A, Varea O, López-Soldado I, Delgado-García JM, Guinovart JJ (2019) Lack of neuronal glycogen impairs memory formation and learning-dependent synaptic plasticity in mice. Front Cell Neurosci. https://doi.org/10.3389/fncel.2019.00374

    Article  PubMed  Google Scholar 

  122. Duran J, Saez I, Gruart A, Guinovart JJ, Delgado-Garcia JM (2013) Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain. J Cereb Blood Flow Metab 33:550–556

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Müller MS, Fox R, Schousboe A, Waagepetersen HS, Bak LK (2014) Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis. Glia 62:526–534

    PubMed  Google Scholar 

  124. Bak LK, Johansen ML, Schousboe A, Waagepetersen HS (2012) Valine but not leucine or isoleucine supports neurotransmitter glutamate synthesis during synaptic activity in cultured cerebellar neurons. J Neurosci Res 90:1768–1775

    CAS  PubMed  Google Scholar 

  125. Lowry OH, Passonneau JV (1964) The relationships between substrates and enzymes of glycolysis in brain. J Biol Chem 239:31–42

    CAS  PubMed  Google Scholar 

  126. Lowry OH, Passonneau JV, Hasselberger FX, Schulz DW (1964) Effect of ischemia on known substrates and cofactors of the glycolytic pathway in brain. J Biol Chem 239:18–30

    CAS  PubMed  Google Scholar 

  127. Dienel GA, Cruz NF, Adachi K, Sokoloff L, Holden JE (1997) Determination of local brain glucose level with [14C]methylglucose: effects of glucose supply and demand. Am J Physiol 273:E839–849

    CAS  PubMed  Google Scholar 

  128. Paschen W, Mies G, Hossmann KA (1992) Threshold relationship between cerebral blood flow, glucose utilization, and energy metabolites during development of stroke in gerbils. Exp Neurol 117:325–333

    CAS  PubMed  Google Scholar 

  129. Paschen W, Hossmann KA, van den Kerckhoff W (1983) Regional assessment of energy-producing metabolism following prolonged complete ischemia of cat brain. J Cereb Blood Flow Metab 3:321–329

    CAS  PubMed  Google Scholar 

  130. Zhu XH, Lee BY, Chen W (2018) Functional energetic responses and individual variance of the human brain revealed by quantitative imaging of adenosine triphosphate production rates. J Cereb Blood Flow Metab 38:959–972

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Du F, Zhu X-H, Zhang Y, Friedman M, Zhang N, Uğurbil K, Chen W (2008) Tightly coupled brain activity and cerebral ATP metabolic rate. Proc Natl Acad Sci USA 105:6409–6414

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Kleinridders A, Ferris HA, Reyzer ML, Rath M, Soto M, Manier ML, Spraggins J, Yang Z, Stanton RC, Caprioli RM, Kahn CR (2018) Regional differences in brain glucose metabolism determined by imaging mass spectrometry. Mol Metab 12:113–121

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Veech RL, Harris RL, Veloso D, Veech EH (1973) Freeze-blowing: a new technique for the study of brain in vivo. J Neurochem 20:183–188

    CAS  PubMed  Google Scholar 

  134. Miller AL, Hawkins RA, Veech RL (1975) Decreased rate of glucose utilization by rat brain in vivo after exposure to atmospheres containing high concentrations of CO2. J Neurochem 25:553–558

    CAS  PubMed  Google Scholar 

  135. Ponten U, Ratcheson RA, Salford LG, Siesjo BK (1973) Optimal freezing conditions for cerebral metabolites in rats. J Neurochem 21:1127–1138

    CAS  PubMed  Google Scholar 

  136. Ponten U, Ratcheson RA, Siesjo BK (1973) Metabolic changes in the brains of mice frozen in liquid nitrogen. J Neurochem 21:1211

    CAS  PubMed  Google Scholar 

  137. Chapman AG, Meldrum BS, Siesjö BK (1977) Cerebral metabolic changes during prolonged epileptic seizures in rats. J Neurochem 28:1025–1035

    CAS  PubMed  Google Scholar 

  138. Duffy TE, Howse DC, Plum F (1975) Cerebral energy metabolism during experimental status epilepticus. J Neurochem 24:925–934

    CAS  PubMed  Google Scholar 

  139. Hertz L, Drejer J, Schousboe A (1988) Energy metabolism in glutamatergic neurons, GABAergic neurons and astrocytes in primary cultures. Neurochem Res 13:605–610

    CAS  PubMed  Google Scholar 

  140. Winkler U, Seim P, Enzbrenner Y, Köhler S, Sicker M, Hirrlinger J (2017) Activity-dependent modulation of intracellular ATP in cultured cortical astrocytes. J Neurosci Res 95:2172–2181

    CAS  PubMed  Google Scholar 

  141. Rangaraju V, Calloway N, Ryan Timothy A (2014) Activity-driven local ATP synthesis is required for synaptic function. Cell 156:825–835

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Harris KM, Weinberg RJ (2012) Ultrastructure of synapses in the mammalian brain. Cold Spring Harb Perspect Biol 4:a005587

    PubMed  PubMed Central  Google Scholar 

  143. Sheng M, Hoogenraad CC (2007) The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu Rev Biochem 76:823–847

    CAS  PubMed  Google Scholar 

  144. Chavan V, Willis J, Walker SK, Clark HR, Liu X, Fox MA, Srivastava S, Mukherjee K (2015) Central presynaptic terminals are enriched in ATP but the majority lack mitochondria. PLoS ONE 10:e0125185

    PubMed  PubMed Central  Google Scholar 

  145. Van Schaftingen E, Veiga-da-Cunha M, Linster CL (2015) Enzyme complexity in intermediary metabolism. J Inherit Metab Dis 38:721–727

    PubMed  Google Scholar 

  146. Beutler E, Dyment P, Matsumoto F (1978) Hereditary nonspherocytic hemolytic anemia and hexokinase deficiency. Blood 51:935–940

    CAS  PubMed  Google Scholar 

  147. Rijksen G, Akkerman J, van den Wall BA, Hofstede D, Staal G (1983) Generalized hexokinase deficiency in the blood cells of a patient with nonspherocytic hemolytic anemia. Blood 61:12–18

    CAS  PubMed  Google Scholar 

  148. Koralkova P, Mojzikova R, van Oirschot B, Macartney C, Timr P, Vives Corrons JL, Striezencova Laluhova Z, Lejhancova K, Divoky V, van Wijk R (2016) Molecular characterization of six new cases of red blood cell hexokinase deficiency yields four novel mutations in HK1. Blood Cells Mol Dis 59:71–76

    CAS  PubMed  Google Scholar 

  149. de Vooght KM, van Solinge WW, van Wesel AC, Kersting S, van Wijk R (2009) First mutation in the red blood cell-specific promoter of hexokinase combined with a novel missense mutation causes hexokinase deficiency and mild chronic hemolysis. Haematologica 94:1203–1210

    PubMed  PubMed Central  Google Scholar 

  150. Hayee BH, Antonopoulos A, Murphy EJ, Rahman FZ, Sewell G, Smith BN, McCartney S, Furman M, Hall G, Bloom SL, Haslam SM, Morris HR, Boztug K, Klein C, Winchester B, Pick E, Linch DC, Gale RE, Smith AM, Dell A, Segal AW (2011) G6PC3 mutations are associated with a major defect of glycosylation: a novel mechanism for neutrophil dysfunction. Glycobiology 21:914–924

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Spiro RG (2002) Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology 12:43R–56R

    CAS  PubMed  Google Scholar 

  152. Gomez-Sanchez EP, Romero DG, de Rodriguez AF, Warden MP, Krozowski Z, Gomez-Sanchez CE (2008) Hexose-6-phosphate dehydrogenase and 11beta-hydroxysteroid dehydrogenase-1 tissue distribution in the rat. Endocrinology 149:525–533

    CAS  PubMed  Google Scholar 

  153. Marcolongo P, Senesi S, Giunti R, Csala M, Fulceri R, Bánhegyi G, Benedetti A (2011) Expression of hexose-6-phosphate dehydrogenase in rat tissues. J Steroid Biochem Mol Biol 126:57–64

    CAS  PubMed  Google Scholar 

  154. Bublitz C, Steavenson S (1988) The pentose phosphate pathway in the endoplasmic reticulum. J Biol Chem 263:12849–12853

    CAS  PubMed  Google Scholar 

  155. Gautam S, Kirschnek S, Gentle IE, Kopiniok C, Henneke P, Hacker H, Malleret L, Belaaouaj A, Hacker G (2013) Survival and differentiation defects contribute to neutropenia in glucose-6-phosphatase-beta (G6PC3) deficiency in a model of mouse neutrophil granulocyte differentiation. Cell Death Differ 20:1068–1079

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Hewitt KN, Walker EA, Stewart PM (2005) Minireview: hexose-6-phosphate dehydrogenase and redox control of 11β-hydroxysteroid dehydrogenase type 1 activity. Endocrinology 146:2539–2543

    CAS  PubMed  Google Scholar 

  157. Servo C, Pitkänen E (1975) Variation in polyol levels in cerebrospinal fluid and serum in diabetic patients. Diabetologia 11:575–580

    CAS  PubMed  Google Scholar 

  158. Servo C, Palo J, Pitkänen E (1977) Gas chromatographic separation and mass spectrometric identification of polyols in human cerebrospinal fluid and plasma. Acta Neurol Scand 56:104–110

    CAS  PubMed  Google Scholar 

  159. Ouchi M, Oba K, Yamashita H, Okazaki M, Tsunoda M, Ohara M, Sekimizu K, Watanabe K, Suzuki T, Nakano H (2012) Effects of sex and age on serum 1,5-anhydroglucitol in nondiabetic subjects. Exp Clin Endocrinol Diabetes 120:288–295

    CAS  PubMed  Google Scholar 

  160. Ouchi M, Oba K, Aoyama J, Watanabe K, Ishii K, Yano H, Motoyama M, Sekimizu K, Matsumura N, Igari Y, Suzuki T, Nakano H (2013) Serum uric acid in relation to serum 1,5-anhydroglucitol levels in patients with and without type 2 diabetes mellitus. Clin Biochem 46:1436–1441

    CAS  PubMed  Google Scholar 

  161. Kametani S, Mizuno H, Shiga Y, Akanuma H (1996) NMR of all-carbon-13 sugars: an application in development of an analytical method for a novel natural sugar, 1, 5-anhydrofructose. J Biochem 119:180–185

    CAS  PubMed  Google Scholar 

  162. Morita M, Akanuma H (1992) Distribution of 1, 5-anhydro-d-glucitol in normal, diabetic, and perfused rat bodies. J Biochem 112:385–388

    CAS  PubMed  Google Scholar 

  163. Mizuno H, Morita M, Akanuma H (1995) Phosphorylation of 1, 5-anhydro-D-glucitol in mammalian cells. J Biochem 118:411–417

    CAS  PubMed  Google Scholar 

  164. Holden JE, Mori K, Dienel GA, Cruz NF, Nelson T, Sokoloff L (1991) Modeling the dependence of hexose distribution volumes in brain on plasma glucose concentration: implications for estimation of the local 2-deoxyglucose lumped constant. J Cereb Blood Flow Metab 11:171–182

    CAS  PubMed  Google Scholar 

  165. Yamanouchi T, Akanuma H, Takaku F, Akanuma Y (1986) Marked depletion of plasma 1,5-anhydroglucitol, a major polyol, in streptozocin-induced diabetes in rats and the effect of insulin treatment. Diabetes 35:204–209

    CAS  PubMed  Google Scholar 

  166. Kametani S, Hashimoto Y, Yamanouchi T, Akanuma Y, Akanuma H (1987) Reduced renal reabsorption of 1, 5-anhydro-D-glucitol in diabetic rats and mice. J Biochem 102:1599–1607

    CAS  PubMed  Google Scholar 

  167. Yamanouchi T, Ogata N, Yoshimura T, Inoue T, Ogata E, Kawasaki T, Kashiwabara A, Muraoka H (2000) Transport of 1,5-anhydro-D-glucitol into insulinoma cells by a glucose-sensitive transport system. Biochim Biophys Acta 1474:291–298

    CAS  PubMed  Google Scholar 

  168. Suzuki M, Akanuma H, Akanuma Y (1988) Transport of 1, 5-anhydro-D-glucitol across plasma membranes in rat henatoma cells. J Biochem 104:956–959

    CAS  PubMed  Google Scholar 

  169. Yamanouchi T, Tachibana Y, Sekino N, Akanuma H, Akaoka I, Miyashita H (1994) Transport and accumulation of 1,5-anhydro-D-glucitol in the human erythroleukemia cell line K-562. J Biol Chem 269:9664–9668

    CAS  PubMed  Google Scholar 

  170. Rees WD, Holman GD (1981) Hydrogen bonding requirements for the insulin-sensitive sugar transport system of rat adipocytes. Biochim Biophys Acta 646:251–260

    CAS  PubMed  Google Scholar 

  171. Taguchi T, Haruna M, Okuda J (1993) Effects of 1,5-anhydro-D-fructose on selected glucose-metabolizing enzymes. Biotechnol Appl Biochem 18:275–283

    CAS  PubMed  Google Scholar 

  172. Hernandez A, Sols A (1963) Transport and phosphorylation of sugars in adipose tissue. Biochem J 86:166–172

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Salas J, Salas M, Viñuela E, Sols A (1965) Glucokinase of rabbit liver: purification and properties. J Biol Chem 240:1014–1018

    CAS  PubMed  Google Scholar 

  174. Carabaza A, Guinovart JJ, Ciudad CJ (1986) Activation of hepatocyte glycogen synthase by metabolic inhibitors. Arch Biochem Biophys 250:469–475

    CAS  PubMed  Google Scholar 

  175. Keston AS (1964) Mutarotase inhibition by 1-deoxyglucose. Science 143:698–700

    CAS  PubMed  Google Scholar 

  176. Bailey JM, Pentchev PG (1965) Inhibition of rat intestinal and rat kidney mutarotase by actively transported sugars. Am J Physiol 208:385–390

    CAS  PubMed  Google Scholar 

  177. Yamanouchi T, Inoue T, Ichiyanagi K, Sakai T, Ogata N (2003) 1,5-Anhydroglucitol stimulates insulin release in insulinoma cell lines. Biochim Biophys Acta 1623:82–87

    CAS  PubMed  Google Scholar 

  178. Tsutsui K, Sakata T, Oomura Y, Arase K, Fukushima M, Hinohara Y (1983) Feeding suppression induced by intra-ventricle III infusion of 1,5-anhydroglucitol. Physiol Behav 31:493–502

    CAS  PubMed  Google Scholar 

  179. Fujimoto K, Sakata T, Terada K, Arase K, Fukushima M, Simpson A (1985) Structural evaluation of anorectic action induced by 1,5-anhydro-D-glucitol. Proc Soc Exp Biol Med 178:515–522

    CAS  PubMed  Google Scholar 

  180. Segel IH (1976) Biochemical calculations. Wiley, New York

    Google Scholar 

  181. Passonneau JV, Lowry OH, Schulz DW, Brown JG (1969) Glucose 1,6-diphosphate formation by phosphoglucomutase in mammalian tissues. J Biol Chem 244:902–909

    CAS  PubMed  Google Scholar 

  182. Yeung PK, Kolathuru SS, Mohammadizadeh S, Akhoundi F, Linderfield B (2018) Adenosine 5′-triphosphate metabolism in red blood cells as a potential biomarker for post-exercise hypotension and a drug target for cardiovascular protection. Metabolites 8:30

    Google Scholar 

  183. Beutler E, Mathai CK (1967) A comparison of normal red cell ATP levels as measured by the firefly system and the hexokinase system. Blood 30:311–320

    CAS  PubMed  Google Scholar 

  184. Hotchkiss RS, Song SK, Neil JJ, Chen RD, Manchester JK, Karl IE, Lowry OH, Ackerman JJ (1991) Sepsis does not impair tricarboxylic acid cycle in the heart. Am J Physiol-Cell Physiol 260:C50–C57

    CAS  Google Scholar 

Download references

Funding

The author received no financial support for the research, authorship, and/or publication of this article.

Author information

Authors and Affiliations

  1. Department of Neurology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Mail Slot 500, Little Rock, AR, 72205, USA

    Gerald A. Dienel

  2. Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA

    Gerald A. Dienel

Authors
  1. Gerald A. Dienel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerald A. Dienel.

Ethics declarations

Conflict of interest

The author declares that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dienel, G.A. Hypothesis: A Novel Neuroprotective Role for Glucose-6-phosphatase (G6PC3) in Brain—To Maintain Energy-Dependent Functions Including Cognitive Processes. Neurochem Res 45, 2529–2552 (2020). https://doi.org/10.1007/s11064-020-03113-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-020-03113-z

Keywords

Search

Navigation