Skip to main content
SpringerLink
Log in

The human embryonic-fetal kidney endoplasmic reticulum phosphate-pyrophosphate transport protein

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Glucose-6-phosphatase is a multicomponent endoplasmic reticulum system comprising at least six different proteins, including a lumenal enzyme and several transport proteins. One of the transport proteins, T2β, transports the substrate pyrophosphate and the product phosphate and its genetic deficiency is termed type 1c glycogen storage disease. We have used anti-T2β antibodies for immunohistochemistry with image analysis and kinetic analysis of the glucose-6-phosphatase system to study for the temporal and spatial development of T2β in human embryonic and fetal kidney. In metanephric kidney, there is an early predominance of T2β expression in the ureteric bud derivatives and this changes with ontogeny such that developing nephrons, particularly proximal tubules, become dominant by mid-gestation. T2β has the same spatial and temporal pattern as the glucose-6-phosphatase enzyme in both mesonephric and metanephric kidney. Pyrophosphate transport capacity is appropriate for the amount of glucose-6-phosphatase activity present in mid-gestation fetal kidney, in contrast to liver, where pyrophosphate transport capacity is developmentally delayed. Increasing knowledge of the temporal and spatial expression of the glucose-6-phosphatase proteins and their catalytic roles in early human development is essential for the elucidation of the aetiology of renal disease in both type I glycogen storage diseases and the developmental disorders of the glucose-6-phosphatase system.

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

Similar content being viewed by others

References

  1. Alon US, Scagliotti D, Garola RE (1994) Nephrocalcinosis and nephrolithiasis in infants with congestive cardiac failure treated with furosemide. J Pediatr 125: 149–151

    Google Scholar 

  2. Arion WJ, Ballas LM, Lange AJ, Wallin BK (1976) Microsomal membrane permeability and the hepatic glucose-6-phosphatase system. J Biol Chem 251: 4901–4907

    Google Scholar 

  3. Arion WJ, Lange AJ, Walls HE, Ballas LM (1980) Evidence for the participation of independent translocases for phosphate and glucose-6-phosphate in the microsomal glucose-6-phosphatase system. J Biol Chem 255: 10396–10406

    Google Scholar 

  4. Ashmore J, Weber G (1959) The role of hepatic glucose-6-phosphatase in the regulation of carbohydrate metabolism. Vitam Horm 17: 91–132

    Google Scholar 

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

    Google Scholar 

  6. Burchell A (1992) The molecular basis of the type 1 glycogen storage diseases. Bioessays 14: 395–400

    Google Scholar 

  7. Burchell A, Cain DI (1985) Rat hepatic microsomal glucose-6-phosphatase protein levels are increased in streptozotocin-induced diabetes. Diabetologia 28: 852–856

    Google Scholar 

  8. Burchell A, Hume R, Burchell B (1988) A new microtechnique for the analysis of the human hepatic microsomal glucose-6-phosphatase system. Clin Chim Acta 173: 183–192

    Google Scholar 

  9. Burchell A, Gibb L, Waddell ID (1989) New microtechniques for the diagnosis of the type 1 glycogen storage diseases. In: Depuy C, Valette L (eds) Perinatal prevention of genomic anomalies. Foundation Marcel Merieux, Lyon, pp 96–103

    Google Scholar 

  10. Burchell A, Gibb L, Waddell ID, Giles M, Hume R (1990) The ontogeny of the human hepatic glucose-6-phosphatase proteins. Clin Chem 36: 1633–1637

    Google Scholar 

  11. Burchell A, Lyall H, Busuttil A, Bell J, Hume R (1992) Glucose metabolism and hypoglycaemia in SIDS. J Clin Pathol 45 [Suppl: 39–45

    Google Scholar 

  12. Burchell A, Allan BB, Hume R (1994) The endoplasmic reticulum glucose-6-phosphatase proteins. Mol Membr Biol 11: 217–227

    Google Scholar 

  13. Chen Y-T (1991) Type I glycogen storage disease: kidney involvement, pathogenesis and its treatment. Pediatr Nephrol 5: 71–76

    Google Scholar 

  14. Chen Y-T, Burchell A (1995) Glycogen storage diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, chapter 24. McGraw-Hill, New York, pp 935–965

    Google Scholar 

  15. Chen Y-T, Coleman RA, Scheinman JI, Kolbede PC, Sidbury JB (1988) Renal disease in type I glycogen storage disease. N Engl J Med 318: 7–11

    Google Scholar 

  16. Colquhoun D (1971) Lectures on biostatistics. Clarendon Press, Oxford, pp 257–265

    Google Scholar 

  17. Cori GT, Cori CF (1952) Glucose-6-phosphatase of the liver in glycogen storage disease. J Biol Chem 199: 661–667

    Google Scholar 

  18. Fulceri R, Romani A, Pompella A, Benedetti A (1990) Glucose-6-phosphate stimulation of MgATP-dependent Ca2+ uptake by rat kidney microsomes. Biochim Biophys Acta 1022: 129–133

    Google Scholar 

  19. Hume R, Burchell A (1993) Abnormal expression of glucose-6-phosphatase in preterm infants. Arch Dis Child 68: 202–204

    Google Scholar 

  20. Hume R, Lyall H, Burchell A (1992) Impairment of the activity of the microsomal glucose-6-phosphatase system in premature infants. Acta Paediatr 81: 580–584

    Google Scholar 

  21. Hume R, Bell JE, Hallas A, Burchell A (1994) Immunohistochemical localisation of glucose-6-phosphatase in developing human kidney. Histochemistry 101: 413–417

    Google Scholar 

  22. Hume R, Voice M, Pazouki S, Giunti R, Benedetti A, Burchell A (1995) The human adrenal microsomal glucose-6-phosphatase system. J Clin Endocrinol Metab 80: 1960–1966

    Google Scholar 

  23. Lucius RW, Waddell ID, Burchell A, Nordlie RC (1993) The hepatic glucose-6-phosphatase system in Ehrlich-ascites-tumour-bearing mice. Biochem J 290: 907–911

    Google Scholar 

  24. Nordlie RC (1976) Glucose-6-phosphate phosphotransferase. In: Mehlman MA, Hanson RW (eds) Gluconeogenesis: its regulation in mammalian species. Wiley, New York, pp 93–152

    Google Scholar 

  25. Nordlie RC (1985) Fine tuning of blood glucose concentrations. Trends Biochem Sci 10: 70–78

    Google Scholar 

  26. Nordlie RC, Scott HM, Waddell ID, Hume R, Burchell A (1992) Analysis of human hepatic microsomal glucose-6-phosphatase in clinical conditions where the T2 pyrophosphate/phosphate transport protein is absent. Biochem J 281: 859–863

    Google Scholar 

  27. Oh W (1981) Renal functions and clinical disorders in the neonate. In: Lewy JE (ed) Symposium on perinatal nephrology. Saunders, Philadelphia, pp 215–223

    Google Scholar 

  28. O'Rahilly R, Muller F (1987) Developmental stages in human embryos. (Publication 637) Carnegie Institution of Washington, Washington, DC

    Google Scholar 

  29. Pears JS, Jung RT, Hopwood D, Waddell ID, Burchell A (1992) Ten cases of symptomatic adult hypoglycaemia due to hepatic glycogen metabolising abnormalities. Q J Med 299: 207–222

    Google Scholar 

  30. Peterson GL (1977) A simplification of the protein method of Lowry et al. which is more generally applicable. Anal Biochem 83: 346–356

    CAS  PubMed  Google Scholar 

  31. Potter EL (1972) Normal and abnormal development in the kidney. Year Book Publishers, Chicago

    Google Scholar 

  32. Restaino I, Kaplan BS, Stanley C, Baker L (1993) Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type I glycogen storage disease. J Pediatr 122: 392–396

    Google Scholar 

  33. Scammon RE, Calkins LA (1929) The development and growth of the external dimensions of the human body in the fetal period. University of Minnesota Press, Minneapolis

    Google Scholar 

  34. Sternberger LA, Hardy PH, Cuculis J, Meyer HG (1970) The unlabelled antibody method of immunohistochemistry: preparation and properties of soluble antigen — antibody complex (horseradish peroxidase-anti-horseradish peroxidase) and its use in identification of spirochaetes. J Histochem Cytochem 18: 315–333

    Google Scholar 

  35. Waddell ID, Lindsay JD, Burchell A (1988) The identification of T2: the phosphate/pyrophosphate transport protein of the hepatic microsomal glucose-6-phosphatase system. FEBS Letts 229: 179–182

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University of Dundee, Ninewells Hospital and Medical School, DD1 9SY, Dundee, UK

    R. Hume, H. Brewerton & A. Burchell

  2. Department of Child Health, University of Dundee, Dundee, UK

    R. Hume

  3. Department of Biochemical Medicine, University of Dundee, Dundee, UK

    R. Hume

Authors
  1. R. Hume
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Brewerton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Burchell
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hume, R., Brewerton, H. & Burchell, A. The human embryonic-fetal kidney endoplasmic reticulum phosphate-pyrophosphate transport protein. Vichows Archiv A Pathol Anat 427, 575–582 (1996). https://doi.org/10.1007/BF00202888

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00202888

Key words

Search

Navigation