Skip to main content
SpringerLink
Log in

Citrate inhibition of rat-kidney cortex phosphofructokinase

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The regulatory properties of citrate on the activity of phosphofructokinase (PFK) purified from rat-kidney cortex has been studied. Citrate produces increases in the K0.5 for Fru-6-P and in the Hill coefficient as well as a decrease in the Vmax of the reaction without affecting the kinetic parameters for ATP as substrate. ATP potentiates synergistically the effects of citrate as an inhibitor of the enzyme. Fru-2,6-P2 and AMP at concentrations equal to Ka were not able to completely prevent citrate inhibition of the enzyme. Physiological concentrations of ATP and citrate produce a strong inhibition of renal PFK suggesting that may participate in the control of glycolysisin vivo.

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

Abbreviations

PFK:

6-Phosphofructo-1-kinase (EC 2.7.1.11)

Fru-6-P:

Fructose 6-phosphate

Fru-2,6-P2 :

Fructose 2,6-bisphosphate

References

  1. Ross BD, Espinal J, Silva P: Glucose metabolism in renal tubular function. Kidney Int 29: 54–67, 1986

    PubMed  Google Scholar 

  2. Pilkis SJ, Granner DK: Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Physiol 54: 885–909, 1992

    PubMed  Google Scholar 

  3. Hue L: Futile cycles and regulation of metabolism. In: H Sies (ed.) Metabolic Compartmentation. Academic Press, New York, 1982, 71–97

    Google Scholar 

  4. Pilkis SJ, El-Maghrabi MR, Claus TH: Hormonal regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Biochem 57: 755–783, 1988

    PubMed  Google Scholar 

  5. Van Schaftingen, E, Jett MF, Hue L, Hers HG: Control of liver 6-phosphofructokinase by fructose-2,6-bisphosphate and others effectors. Proc Natl Acad Sci USA 78: 3483–3486, 1981

    PubMed  Google Scholar 

  6. Claus TH, El-Maghrabi MR, Regen SHB, McGrane M, Kounce PD, Nyfeler F, Pilkis J, Pilkis SJ: The role of fructose 2,6-bisphosphate in the regulation of carbohydrate metabolism. Curr Top Cell Regul 23: 57–86, 1984

    PubMed  Google Scholar 

  7. Hers HG, Hue L: Gluconeogenesis and related aspects of glycolysis. Annu Rev Biochem 52: 617–653, 1983

    PubMed  Google Scholar 

  8. Bloxham DP, Lardy HA: Phosphofructokinase. In: P Boyer (ed.) The Enzymes. 3rd edition, Vol. VIII. Academic Press, New York, 1973, pp 239–278

    Google Scholar 

  9. Uyeda K: Phosphofructokinase. Adv Enzymol 48: 193–244, 1979

    PubMed  Google Scholar 

  10. Kuwajima H, Uyeda K: The tissue distribution of fructose-2,6-bisphosphate and fructose-6-phosphate,2-kinase in rats and the effect of starvation, diabetes and hypoglycemia on hepatic fructose-2,6-bisphosphate and fructose-6-phosphate,2-kinase. Biochem Biophys Res Commun 104: 84–88, 1982

    PubMed  Google Scholar 

  11. Seifter JL, Schubert C: Zonal distribution of fructose-2,6-bisphosphate (Fru 2,6-P2) in the rat kidney. Higher levels in glycolytic medulla then gluconeogenic cortex. Kidney Int 31: 401–406, 1987

    Google Scholar 

  12. Muniyappa K, Leibach FH, Mendicino J: Reciprocal regulation of fructose-1,6-bisphosphatase and phosphofructokinase by fructose-2,6-bisphosphate in swine kidney. Life Sci 32: 271–278, 1983

    PubMed  Google Scholar 

  13. Sola MM, Salto R, Oliver J, Vargas AM: Kinetic characterization of phosphofructokinase isolated from rat kidney cortex. Comp Biochem Physiol 98B: 495–500, 1991

    Google Scholar 

  14. Sola MM, Salto R, Oliver J, Gutiérrez M, Vargas AM: Effects of AMP and fructose 2,6-bisphosphate on fluxes between glucose 6-phosphate and triose-phosphate in renal cortical extracts. J Biol Chem 268: September, 1993

  15. Simpson DP, Hager SR: pH and bicarbonate effects on mitochondrial anion accumulation. Proposed mechanism for changes in renal metabolite levels in acute acid-base disturbances. J Clin Invest 63: 704–712, 1979

    PubMed  Google Scholar 

  16. Cohen JJ, Kamm DE: Renal metabolism: Relation to renal function. In: BM Brenner,FC Rector (eds.) The Kidney. 2nd edition. Saunders, Philadelphia, 1981, pp 144–248

    Google Scholar 

  17. Adler S, Anderson B, Zemotel L: Metabolic acid-base effects on tissue citrate content and metabolism in the rat. Am J Physiol 220: 986–990, 1971

    PubMed  Google Scholar 

  18. Vinay P, Allignet E, Pichette C, Watford M, Lemieux G, Gougoux A: Changes in renal metabolite profile and ammoniogenesis during acute and chronic metabolic acidosis in dog and rat. Kidney Int 17: 312–325, 1980

    PubMed  Google Scholar 

  19. Simpson DP: Regulation of renal citrate metabolism by bicarbonate ion and pH: Observations in tissue slices and mitochondria. J Clin Invest 46: 225–238, 1967

    PubMed  Google Scholar 

  20. Bradford M: A rapid and sensitive method for the quantitation of microgram quantities of proteins utilizing the principle of protein dye binding. Anal Biochem 72: 248–254, 1976

    PubMed  Google Scholar 

  21. Colombo G, Tate PW, Girotti AW, Kemp RG: Interactions of inhibitors with muscle phosphofructokinase. J Biol Chem 250: 9404–9412, 1975

    PubMed  Google Scholar 

  22. Uyeda K, Furuya E, Luby LJ: The effect of natural and synthetic D-Fructose 2,6-bisphosphate on the regulatory kinetic properties of liver and muscle phosphofructokinase. J Biol Chem 256: 8394–8399, 1981

    PubMed  Google Scholar 

  23. Kemp RG, Foe LG: Allosteric regulatory properties of muscle phosphofructokinase. Mol Cell Biochem 57: 147–154, 1983

    PubMed  Google Scholar 

  24. Sochor M, Kunjara S, McLean P: Regulation of pathways of glucose metabolism in the kidney. The activity of the pentose phosphate pathway, glycolytic route and the regulation of phosphofructokinase in the kidney of lean and genetically obese (ob/ob) mice: Comparison with effects of diabetes. Horm Metabol Res 20: 676–681, 1988

    Google Scholar 

  25. Ogawa Y, Atkinson DE: Interactions between citrate and nucleoside triphosphates in binding to phosphofructokinase. Biochemistry 24: 954–958, 1985

    PubMed  Google Scholar 

  26. Costello J, Scott JM, Wilson P, Bourke E: Glucose utilization and production by the dog kidneyin vivo in metabolic acidosis and alkalosis. J Clin Invest 52: 608–612, 1973

    PubMed  Google Scholar 

  27. Relman AA: Metabolic consequences of acid-base disorders. Kidney Int 1: 347–553, 1972

    PubMed  Google Scholar 

  28. Adler S: The role of pH, pCO2, and bicarbonate in regulating rat diaphragm citrate content. J Clin Invest 49: 1647–1650, 1970

    PubMed  Google Scholar 

  29. Dunaway GA: A review of animal phosphofructokinase isozymes with an emphasis on their physiological role. Mol Cell Biochem 52: 75–91, 1983

    PubMed  Google Scholar 

  30. Dunaway GA, Kasten TP: Physiological relevance of the changing subunit composition and regulatory properties of the 6-phosphofructo-1-kinase isozyme pools during heart and muscle development. Mol Cell Biochem 87: 71–77, 1989

    PubMed  Google Scholar 

  31. Mhaskar Y, Dunaway GA: The subunit proportions and kinetic properties of 6-phosphofructo-1-kinase isozymes from rat heart atria and ventricle progressively change during aging. Mol Cell Biochem 107: 39–45, 1991

    PubMed  Google Scholar 

  32. Pogson CI, Longshaw ID, Roobol A, Smith SA, Alleyne GAO: Phosphoenolpyruvate carboxykinase and renal gluconeogenesis. In: RW Hanson, MA Mehlman (eds.) Gluconeogenesis: its regulation in mammalian species. John Wiley & Sons, New York, 1976, pp 335–368

    Google Scholar 

  33. Vargas AM, Lupiani MJ, Lupiañez JA, Sánchez-Medina F: Stimulation of rat renal phosphaenolpyruvate carboxykinase activity after an intravenous lactic acid load. FEBS Lett 127: 121–124, 1981

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departmento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, Avda. Fuentenueva s/n, 18071, Granada, Spain

    María M. Sola, F. Javier Oliver, Rafael Salto, Margarita Gutiérrez & Alberto Vargas

Authors
  1. María M. Sola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Javier Oliver
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rafael Salto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Margarita Gutiérrez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alberto Vargas
    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

Sola, M.M., Oliver, F.J., Salto, R. et al. Citrate inhibition of rat-kidney cortex phosphofructokinase. Mol Cell Biochem 135, 123–128 (1994). https://doi.org/10.1007/BF00926514

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00926514

Key words

Search

Navigation