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. 2001 Jul 15;357(Pt 2):557–562. doi: 10.1042/0264-6021:3570557

Glucose 6-phosphate transport in fibroblast microsomes from glycogen storage disease type 1b patients: evidence for multiple glucose 6-phosphate transport systems.

R Leuzzi 1, R Fulceri 1, P Marcolongo 1, G Bánhegyi 1, E Zammarchi 1, K Stafford 1, A Burchell 1, A Benedetti 1
PMCID: PMC1221985  PMID: 11439108

Abstract

In liver endoplasmic reticulum the intralumenal glucose-6-phosphatase activity requires the operation of a glucose 6-phosphate transporter (G6PT1). Mutations in the gene encoding G6PT1 cause glycogen storage disease type 1b, which is characterized by a loss of glucose-6-phosphatase activity and impaired glucose homoeostasis. We describe a novel glucose 6-phosphate (G6P) transport activity in microsomes from human fibroblasts and HeLa cells. This transport activity is unrelated to G6PT1 since: (i) it was similar in microsomes of skin fibroblasts from glycogen storage disease type 1b patients homozygous for mutations of the G6PT1 gene, and in microsomes from human control subjects; (ii) it was insensitive to the G6PT1 inhibitor chlorogenic acid; and (iii) it was equally active towards G6P and glucose 1-phosphate, whereas G6PT1 is highly selective for G6P. Taken together, our results provide evidence for the presence of multiple transporters for G6P (and other hexose phosphoesters) in the endoplasmic reticulum.

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Selected References

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  1. Arion W. J., Canfield W. K., Ramos F. C., Schindler P. W., Burger H. J., Hemmerle H., Schubert G., Below P., Herling A. W. Chlorogenic acid and hydroxynitrobenzaldehyde: new inhibitors of hepatic glucose 6-phosphatase. Arch Biochem Biophys. 1997 Mar 15;339(2):315–322. doi: 10.1006/abbi.1996.9874. [DOI] [PubMed] [Google Scholar]
  2. Arion W. J., Lange A. J., Walls H. E., Ballas L. M. Evidence for the participation of independent translocation for phosphate and glucose 6-phosphate in the microsomal glucose-6-phosphatase system. Interactions of the system with orthophosphate, inorganic pyrophosphate, and carbamyl phosphate. J Biol Chem. 1980 Nov 10;255(21):10396–10406. [PubMed] [Google Scholar]
  3. Bublitz C., Steavenson S. The pentose phosphate pathway in the endoplasmic reticulum. J Biol Chem. 1988 Sep 15;263(26):12849–12853. [PubMed] [Google Scholar]
  4. Bánhegyi G., Marcolongo P., Burchell A., Benedetti A. Heterogeneity of glucose transport in rat liver microsomal vesicles. Arch Biochem Biophys. 1998 Nov 1;359(1):133–138. doi: 10.1006/abbi.1998.0888. [DOI] [PubMed] [Google Scholar]
  5. Bánhegyi G., Marcolongo P., Fulceri R., Hinds C., Burchell A., Benedetti A. Demonstration of a metabolically active glucose-6-phosphate pool in the lumen of liver microsomal vesicles. J Biol Chem. 1997 May 23;272(21):13584–13590. doi: 10.1074/jbc.272.21.13584. [DOI] [PubMed] [Google Scholar]
  6. Chen L. Y., Lin B., Pan C. J., Hiraiwa H., Chou J. Y. Structural requirements for the stability and microsomal transport activity of the human glucose 6-phosphate transporter. J Biol Chem. 2000 Nov 3;275(44):34280–34286. doi: 10.1074/jbc.M006439200. [DOI] [PubMed] [Google Scholar]
  7. Chen P. Y., Csutora P., Veyna-Burke N. A., Marchase R. B. Glucose-6-phosphate and Ca2+ sequestration are mutually enhanced in microsomes from liver, brain, and heart. Diabetes. 1998 Jun;47(6):874–881. doi: 10.2337/diabetes.47.6.874. [DOI] [PubMed] [Google Scholar]
  8. Collard F., Collet J. F., Gerin I., Veiga-da-Cunha M., Van Schaftingen E. Identification of the cDNA encoding human 6-phosphogluconolactonase, the enzyme catalyzing the second step of the pentose phosphate pathway(1). FEBS Lett. 1999 Oct 8;459(2):223–226. doi: 10.1016/s0014-5793(99)01247-8. [DOI] [PubMed] [Google Scholar]
  9. Forsyth R. J., Bartlett K., Burchell A., Scott H. M., Eyre J. A. Astrocytic glucose-6-phosphatase and the permeability of brain microsomes to glucose 6-phosphate. Biochem J. 1993 Aug 15;294(Pt 1):145–151. doi: 10.1042/bj2940145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fulceri R., Gamberucci A., Scott H. M., Giunti R., Burchell A., Benedetti A. Fatty acyl-CoA esters inhibit glucose-6-phosphatase in rat liver microsomes. Biochem J. 1995 Apr 15;307(Pt 2):391–397. doi: 10.1042/bj3070391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Galli L., Orrico A., Marcolongo P., Fulceri R., Burchell A., Melis D., Parini R., Gatti R., Lam C., Benedetti A. Mutations in the glucose-6-phosphate transporter (G6PT) gene in patients with glycogen storage diseases type 1b and 1c. FEBS Lett. 1999 Oct 8;459(2):255–258. doi: 10.1016/s0014-5793(99)01248-x. [DOI] [PubMed] [Google Scholar]
  12. Gamberucci A., Marcolongo P., Fulceri R., Giunti R., Watkins S. L., Waddell I. D., Burchell A., Benedetti A. Low levels of glucose-6-phosphate hydrolysis in the sarcoplasmic reticulum of skeletal muscle: involvement of glucose-6-phosphatase. Mol Membr Biol. 1996 Apr-Jun;13(2):103–108. doi: 10.3109/09687689609160583. [DOI] [PubMed] [Google Scholar]
  13. Gerin I., Veiga-da-Cunha M., Achouri Y., Collet J. F., Van Schaftingen E. Sequence of a putative glucose 6-phosphate translocase, mutated in glycogen storage disease type Ib. FEBS Lett. 1997 Dec 15;419(2-3):235–238. doi: 10.1016/s0014-5793(97)01463-4. [DOI] [PubMed] [Google Scholar]
  14. Gerin I., Veiga-da-Cunha M., Noël G., Van Schaftingen E. Structure of the gene mutated in glycogen storage disease type Ib. Gene. 1999 Feb 18;227(2):189–195. doi: 10.1016/s0378-1119(98)00614-3. [DOI] [PubMed] [Google Scholar]
  15. Hino Y., Minakami S. Hexose-6-phosphate and 6-phosphogluconate dehydrogenases of rat liver microsomes. Involvement in NADPH and carbon dioxide generation in the luminal space of microsomal vesicles. J Biochem. 1982 Aug;92(2):547–557. doi: 10.1093/oxfordjournals.jbchem.a133963. [DOI] [PubMed] [Google Scholar]
  16. Hiraiwa H., Pan C. J., Lin B., Moses S. W., Chou J. Y. Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b. J Biol Chem. 1999 Feb 26;274(9):5532–5536. doi: 10.1074/jbc.274.9.5532. [DOI] [PubMed] [Google Scholar]
  17. Hume R., Voice M., Pazouki S., Giunti R., Benedetti A., Burchell A. The human adrenal microsomal glucose-6-phosphatase system. J Clin Endocrinol Metab. 1995 Jun;80(6):1960–1966. doi: 10.1210/jcem.80.6.7775646. [DOI] [PubMed] [Google Scholar]
  18. Kramer W., Burger H. J., Arion W. J., Corsiero D., Girbig F., Weyland C., Hemmerle H., Petry S., Habermann P., Herling A. Identification of protein components of the microsomal glucose 6-phosphate transporter by photoaffinity labelling. Biochem J. 1999 May 1;339(Pt 3):629–638. [PMC free article] [PubMed] [Google Scholar]
  19. Kure S., Hou D. C., Suzuki Y., Yamagishi A., Hiratsuka M., Fukuda T., Sugie H., Kondo N., Matsubara Y., Narisawa K. Glycogen storage disease type Ib without neutropenia. J Pediatr. 2000 Aug;137(2):253–256. doi: 10.1067/mpd.2000.107472. [DOI] [PubMed] [Google Scholar]
  20. Kure S., Suzuki Y., Matsubara Y., Sakamoto O., Shintaku H., Isshiki G., Hoshida C., Izumi I., Sakura N., Narisawa K. Molecular analysis of glycogen storage disease type Ib: identification of a prevalent mutation among Japanese patients and assignment of a putative glucose-6-phosphate translocase gene to chromosome 11. Biochem Biophys Res Commun. 1998 Jul 20;248(2):426–431. doi: 10.1006/bbrc.1998.8985. [DOI] [PubMed] [Google Scholar]
  21. Li Y., Méchin M. C., van de Werve G. Diabetes affects similarly the catalytic subunit and putative glucose-6-phosphate translocase of glucose-6-phosphatase. J Biol Chem. 1999 Nov 26;274(48):33866–33868. doi: 10.1074/jbc.274.48.33866. [DOI] [PubMed] [Google Scholar]
  22. Lin B., Annabi B., Hiraiwa H., Pan C. J., Chou J. Y. Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents. J Biol Chem. 1998 Nov 27;273(48):31656–31660. doi: 10.1074/jbc.273.48.31656. [DOI] [PubMed] [Google Scholar]
  23. Marcolongo P., Barone V., Priori G., Pirola B., Giglio S., Biasucci G., Zammarchi E., Parenti G., Burchell A., Benedetti A. Structure and mutation analysis of the glycogen storage disease type 1b gene. FEBS Lett. 1998 Oct 2;436(2):247–250. doi: 10.1016/s0014-5793(98)01129-6. [DOI] [PubMed] [Google Scholar]
  24. Meissner G., Allen R. Evidence for two types of rat liver microsomes with differing permeability to glucose and other small molecules. J Biol Chem. 1981 Jun 25;256(12):6413–6422. [PubMed] [Google Scholar]
  25. Middleditch C., Clottes E., Burchell A. A different isoform of the transport protein mutated in the glycogen storage disease 1b is expressed in brain. FEBS Lett. 1998 Aug 14;433(1-2):33–36. doi: 10.1016/s0014-5793(98)00878-3. [DOI] [PubMed] [Google Scholar]
  26. Morrissey J. H. Silver stain for proteins in polyacrylamide gels: a modified procedure with enhanced uniform sensitivity. Anal Biochem. 1981 Nov 1;117(2):307–310. doi: 10.1016/0003-2697(81)90783-1. [DOI] [PubMed] [Google Scholar]
  27. Nordlie R. C., Foster J. D., Lange A. J. Regulation of glucose production by the liver. Annu Rev Nutr. 1999;19:379–406. doi: 10.1146/annurev.nutr.19.1.379. [DOI] [PubMed] [Google Scholar]
  28. Puskás F., Marcolongo P., Watkins S. L., Mandl J., Allan B. B., Houston P., Burchell A., Benedetti A., Bánhegyi G. Conformational change of the catalytic subunit of glucose-6-phosphatase in rat liver during the fetal-to-neonatal transition. J Biol Chem. 1999 Jan 1;274(1):117–122. doi: 10.1074/jbc.274.1.117. [DOI] [PubMed] [Google Scholar]
  29. Veiga-da-Cunha M., Gerin I., Chen Y. T., Lee P. J., Leonard J. V., Maire I., Wendel U., Vikkula M., Van Schaftingen E. The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a. Eur J Hum Genet. 1999 Sep;7(6):717–723. doi: 10.1038/sj.ejhg.5200366. [DOI] [PubMed] [Google Scholar]
  30. Veiga-da-Cunha M., Gerin I., Chen Y. T., de Barsy T., de Lonlay P., Dionisi-Vici C., Fenske C. D., Lee P. J., Leonard J. V., Maire I. A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. Am J Hum Genet. 1998 Oct;63(4):976–983. doi: 10.1086/302068. [DOI] [PMC free article] [PubMed] [Google Scholar]

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