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Phosphate Depletion and Adenine Nucleotide Metabolism in Kidney and Liver

  • K. Kurokawa
  • W. J. Kreusser
  • S. G. Massry
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 103)

Abstract

Adenosine triphosphate (ATP) and other adenine nucleotides are the major energy coupling mechanism between the energy-producing and the energy-consuming systems in the cells. In a variety of diseased states, an altered metabolism of adenine nucleotides has been implicated in their pathogenesis. There are a few experimental model systems in which one can alter adenine nucleotide metabolism through a different mechanism and study the role of adenine nucleotides in cell functions as shown in Table 1 (1). Although studies using the first three models have been extensively performed, effects of phosphate depletion on the metabolism of adenosine triphosphate and other phosphate compounds in various organ systems have been studied rather to a lesser extent except in red cells, leukocytes, and platelets, where the relationship between a fall in plasma inorganic phosphate (Pi), a fall in tissue Pi, a decrease in tissue ATP, and some forms of cellular dysfunction have been demonstrated (2). Since a major portion of ATP is synthesized from ADP and Pi by oxidative phosphorylation in mitochondria, a deficiency of Pi will result in an impairment of ATP generation. Thus, various organ dysfunctions described in phosphate depletion have been attributed to a fall in the availability of energy-rich phosphate compounds such as ATP. Nevertheless, data on the changes in levels of adenine nucleotides and Pi in different organ systems are limited.

Keywords

Adenine Nucleotide Adenosine Triphosphate Energy Charge Adenylate Kinase Orotic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Farber, E.: ATP and cell integrity. Fed. Proc. 32:1534, 1973.Google Scholar
  2. 2.
    Knochel, J.P.: The pathophysiology and clinical characteristics of severe hypophosphatemia. Arch. Int. Med. 137: 203, 1977.CrossRefGoogle Scholar
  3. 3.
    Coburn, J.W., and Massry, S.G.: Changes in serum and urinary calcium during phosphate depletion: Studies on mechanisms. J. Clin. Invest. 1+9: 1073, 1970.Google Scholar
  4. 4.
    Troehler, U., Bonjour, J.P., and Fleisch, H.: Inorganic phosphate homeostasis. Renal adaptation to the dietary intake in intact and thyroparathyroidectomized rats. J. Clin. Invest. 57: 264, 1976.CrossRefGoogle Scholar
  5. 5.
    Steele, T.H., and DeLuca, H.F.: Influence of dietary phosphate on renal phosphate reabsorption in the parathyroidectomized rat. J. Clin. Invest. 57: 867, 1976.PubMedCrossRefGoogle Scholar
  6. 6.
    Gold, L.M., Massry, S.G., Arieff, A.I., and Coburn, J.W.: Renal bicarbonate wasting during phosphate depldtion. A possible cause of altered acid-base homeostasis in hyperparathyroidism. J. Clin. Invest. 52: 2556, 1973.PubMedCrossRefGoogle Scholar
  7. 7.
    Harter, H.R., Mercado, A., Rutherford, W.E., Rodriguez, H., Slatopolsky, E., and Klahr, S.: Effects of phosphate depletion and parathyroid hormone on renal glucose reabsorption. Am. J. Physiol. 227: 1422, 1974.PubMedGoogle Scholar
  8. 8.
    Goldfarb, S., Westby, G.R., Goldberg, M., and Agus, Z.S.: Renal tubular effects of chronic phosphate depletion. J. Clin. Invest. 59: 770, 1977.PubMedCrossRefGoogle Scholar
  9. 9.
    Gold, L.M., Massry, S.G., and Friedler, R.M.: Effect of phosphate depletion on renal tubular reabsorption of glucose. J. Lab. Clin. Med. 89: 554, 1977.PubMedGoogle Scholar
  10. 10.
    Tanaka, Y., and DeLuca, H.F.: The control of 25-hydroxyvitamin D metabolism by inorganic phosphorus. Arch. Biochem. Biophys. 154: 566, 1973.PubMedCrossRefGoogle Scholar
  11. 11.
    Williamson, J.R., and Herczeg, B.E.: Assays of intermediates of the citric acid cycle and related compounds by fluorometric enzyme method; In, Lowenstein, J.M. 9ed.), Methods in Enzymology Vol 13, New York, Academic Press, p. 434, 1969.Google Scholar
  12. 12.
    Hems, D.A., and Brosnan, J.T.: Effects of ischaemia on content of metabolites in rat liver and kidney in vivo. Biochem. J. 120: 105, 1970.PubMedGoogle Scholar
  13. 13.
    Hohorst, H.J., Kreutz, F.H., and Bücher, T.: Uber Metabolitge-halte und Metabolit-Konzentrationen in der Leber der Ratte. Biochem. Z. 332: 18, 1959.Google Scholar
  14. 14.
    Bucher, N.L.R., and Swaffield, M.M.: Nucleotide pools and (6–14C) orotic acid incorporation in early regenerating rat liver. Biochim. Biophys. Acta 129: 445, 1966.PubMedCrossRefGoogle Scholar
  15. 15.
    Nagata, N., and Rasmussen, H.: Parathyroid hormone and renal cell metabolism. Biochemistry 7: 3728, 1968.PubMedCrossRefGoogle Scholar
  16. 16.
    Schulz, D.W., Passonneau, J.V., and Lowry, 0.H.: An enzymatic method for the measurement of inorganic phosphate. Anal. Biochem. 19: 300, 1967.PubMedCrossRefGoogle Scholar
  17. 17.
    Chen, P.S., Toribara, T.Y., and Warner, H.: Microdetermination of phosphorus. Anal. Chem. 28: 1756, 1956.CrossRefGoogle Scholar
  18. 18.
    Atkinson, D.E.: The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry 7: 4030, 1968.PubMedCrossRefGoogle Scholar
  19. 19.
    Lichtman, M.A., Miller, D.R., and Freeman, R.B.: Erythrocyte adenosine triphosphate depletion during hypophosphatemia in a uremic•subject. New Engl. J. Med. 280: 240, 1969.Google Scholar
  20. 20.
    Lichtman, M.A., Miller, D.R., Cohen, J., and Waterhouse, C.: Reduced red cell glycolysis, 2,3-diphosphoglycerate and adenosine triphosphate concentration, and increased hemoglobin oxygen affinity caused by hypophosphatemia. Ann. Int. Med. 74: 562, 1971.PubMedGoogle Scholar
  21. 21.
    Wu, R.: Rate-limiting factors in glycolysis and inorganic orthophosphate transport in rat liver and kidney slices. J. Biol. Chem. 240: 2373, 1965.PubMedGoogle Scholar
  22. 22.
    DeLuca, H:F.: Recent advances in our understanding of the vitamin D endocrine system. J. Lab. Clin. Med. 87: 7, 1976.Google Scholar
  23. 23.
    Birge, S.J., and Haddad, J.G.: 25-hydroxycholecalciferol stimulation of muscle metabolism. J. Clin. Invest. 56: 1100, 1975.PubMedCrossRefGoogle Scholar
  24. 24.
    Hughes, M.R., Brumbaugh, P.F., Haussler, M.R., Wergedal, J.E., and Baylink, D.J.: Regulation of serum la,25-dihydroxyvitamin D3 by calcium and phosphate in the rat. Science 190: 578, 1975.PubMedCrossRefGoogle Scholar
  25. 25.
    Maenpaa, P.H., Raivio, K.O., and Kekomaki, M.P.: Liver adenine nucleotides: Fructose-induced depletion and its effect on protein synthesis. Science 161: 1253, 1968.PubMedCrossRefGoogle Scholar
  26. 26.
    Burch, H.B., Lowry, 0.H., Meinhardt, L., Max, P., and Chyu, K.: Effect of fructose, dihydroxyacetone, glycerol and glucose on metabolites and related compounds in liver and kidney. J. Biol. Chem. 245: 5092, 1970.Google Scholar
  27. 27.
    Chapman, A.G., and Atkinson, D.E.: Stabilization of adenylate energy charge by the adenylate deaminase reaction. J. Biol. Chem. 248: 8309, 1973.PubMedGoogle Scholar
  28. 28.
    Woods, H.F., Eggleston, L.V., and Krebs, H.A.: The cause of hepatic accumulation of fructose-l-phosphate on fructose loading. Biochem. J. 119: 501, 1970.PubMedGoogle Scholar
  29. 29.
    Froesch, E.R.: Essential fructosuria and hereditary fructose intolerance. In, Stanbury, J.B., Syngaarden, J.B. and Fredrickson, D.S. (eds.), The Metabolic Basis of Inherited Disease, p. 131, McGraw-Hill, 1972.Google Scholar
  30. 30.
    Ross, I.A.: The state of magnesium in cells as estimated from the adenylate kinase equilibrium. Proc. Natl. Acad. Sci. U.S.A. 61: 1079, 1968.CrossRefGoogle Scholar
  31. 31.
    Blair, J.M. Metal ions and enzyme equilibria. A mathematical treatment. FEES Letters 1: 100, 1968.CrossRefGoogle Scholar
  32. 32.
    Kreusser, W.J., Kurokawa, K., Aznar, E., Sachtjen, E., and Massry, S.G Effect of phosphate depletion on magnesium homeostasis. J. Clin. Invest. 61: (ín press), 1978.Google Scholar
  33. 33.
    Dominguez, J.H., Gray, R.W., and Lemann, J.J.: Dietary phosphate deprivation in women and men: Effects on mineral and acid balances, parathyroid hormone, and the metabolism of 25-OH-vitamin D. J. Clin. Endocrinol. Metab. 43: 1056, 1976.PubMedCrossRefGoogle Scholar
  34. 34.
    Kreusser, W.J., Kurokawa, K., and Massry, S.G.: Unpublished observation.Google Scholar
  35. 35.
    Thiers, R.E., and Vallee, B.L.: Distribution of metals in sub-cellular fractions of rat liver. J. Biol. Chem. 226: 911, 1957.PubMedGoogle Scholar
  36. 36.
    Oscai, L.B., and Holloszy, J.O.: Biochemical adaption in muscle. II. Response of mitochondrial adenosine triphosphatase, creatine phosphokinase, and adenylate kinase activities in skeletal muscle to exercise. J. Biol. Chem. 246: 6968, 1971.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • K. Kurokawa
    • 1
  • W. J. Kreusser
    • 1
  • S. G. Massry
    • 1
  1. 1.University of Southern California School of MedicineLos AngelesUSA

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