Skip to main content

Advertisement

Log in

ATP formation from deoxyadenosine in human erythrocytes: Evidence for a hitherto unidentified route involving adenine and S-adenosylhomocysteine hydrolase

  • Short Papers
  • Published:
Bioscience Reports

Abstract

A novel route of ATP formation has been identified using erythrocytes from patients deficient in four different enzymes associated with ATP formation. It entails prior adenine production from deoxyadenosine (or adenosine) in a reaction involving S-adenosylhomocysteine hydrolase. The postulated route has been demonstrated in human erythrocytes which, unlike other human cells, cannot form ATP from IMP. It is based on studies by others using purified S-adenosylhomocysteine hydrolase preparationsin vitro. The results provide the first confirmation that this reaction occurs in intact human cellsin vitro and thus most probablyin vivo. This adenine production is normally masked in intact cells by further metabolism to ATP. Clinical significance for such a route is suggested by the fact that some adenosine analogues with potent oncostatic and antiviral properties also release adenine (or analogues)in vitro.

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

Access this article

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

Instant access to the full article PDF.

References

  1. Kredich, N. M. and Hershfield, M. S. (1983) Immunodeficiency diseases caused by adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency. In:The Metabolic Basis of Inherited Disease, Chapter 43 (Stanbury, J. B., Wyngaarden, J. B., Fredrickson, D. S., Goldstein, J. L. and Brown, M. S., eds.) Plenum Press, NY, pp. 1157–1183.

    Google Scholar 

  2. Morgan, G., Levinsky, R. J., Hugh-Jones, K., Fairbanks, L. D., Morris, G. S. and Simmonds, H. A. (1987) Heterogeneity of biochemical, clinical and immunological parameters in severe combined immunodeficiency due to adenosine deaminase deficiency.Clin. exp. Immunol. 70:491–499.

    Google Scholar 

  3. Simmonds, H. A., Panayi, G. S. and Corrigal, V. (1978) A role for purine metabolism in the immune response: adenosine deaminase activity and deoxyadenosine catabolism.Lancet 1:60–63.

    Google Scholar 

  4. Hershfield, M. S. (1979) Apparent suicide inactivation of human lymphoblast S-adenosylhomocysteine hydrolase by 2′-deoxyadenosine and adenine arabinoside. A basis for direct toxic effects of analogs of adenosine.J. Biol. Chem. 254:22–25.

    Google Scholar 

  5. Fairbanks, L. D., Simmonds, H. A. and Webster D. R. (1987) Use of intact erythrocytes in the diagnosis of inherited purine and pyrimidine disorders.J. Inher. Metab. Dis. 10:174–187.

    Google Scholar 

  6. Simmonds, H. A., Goday, A., Morris, G. S. and Brolsma, F. J. (1984) Metabolism of deoxynucleosides by lymphocytes in long-term culture deficient in different purine enzymes.Biochem. Pharmacol. 33:763–770.

    Google Scholar 

  7. Bishop, C. (1960) Purine metabolism in human and chicken bloodin vitro.J. Biol. Chem. 235:3228–3232.

    Google Scholar 

  8. Abeles, R. H., Tashjian, A. H. and Fish, S. (1980) The mechanism of inactivation of S-adenosylhomocysteinase by 2′-deoxyadenosine.Biochem. Biophys. Res. Comm. 95:612–617.

    Google Scholar 

  9. Hohman, R. J., Guitton, M. C. and Veron, M. (1984) Purification of S-adenosyl-1-homocysteine hydrolase from Dictyostelium discoideum: Reversible inactivation by cAMP and 2′-deoxyadenosine.Arch. Biochem. Biophys. 233:785–795.

    Google Scholar 

  10. Simmonds, H. A., Fairbanks, L. D., Morris, G. S., Morgan, G., Watson, A. R., Timms, P. and Singh, B. (1987) CNS dysfunction and erythrocyte GTP depletion in purine nucleoside phosphorylase deficiency.Arch. Dis. Child. 62:385–391.

    Google Scholar 

  11. Simmonds, H. A. and Van Acker, K. J. (1983) Adenine phosphoribosyltransferase deficiency: 2,8-dihydroxyadenine lithiasis. In:The Metabolic Basis of Inherited Disease, Chapter 42 (Stanbury, J. B., Wyngaarden, J. B., Fredrickson, D. S., Goldstein, J. L. and Brown, M. S., eds.) Plenum Press, NY, 5th edition, pp. 1144–1156.

    Google Scholar 

  12. Meyskens, F. I. and Williams, H. E. (1971) Adenosine metabolism in human erythrocytes.Biochem. Biophys. Acta 240:170–179.

    Google Scholar 

  13. Mills, G. C., Goldblum, R. M. and Schmalsteig, F. C. (1981) Catabolism of adenine nucleotides in adenosine deaminase deficient erythrocytes.Life Sci. 29:1811–1820.

    Google Scholar 

  14. Bontemps, F., Van den Berghe, G. and Hers, H. G. (1986) Pathways of adenine catabolism in erythrocytes.J. Clin. Invest. 77:824–830.

    Google Scholar 

  15. Gerber, G., Werner, A., Rapoport, I. and Siems, W. (1987) Analysis of nucleotide metabolism in red blood cells by reversed-phase HPLC.Klin. Wochenschr. 65.

  16. Cartier, P., Hamet, M., Vincens, A. and Perignon, J. L. (1980) Complete adenine phosphoribosyltransferase (APRT) deficiency in two siblings: report of a new case.Adv. Exp. Med. Biol. 122A:343–348.

    Google Scholar 

  17. Ueland, P. M. and Doskeland, S. O. (1977) An adenosine 3′:5′-monophosphate-adenosine binding protein from mouse liver.J. Biol. Chem. 252:677–686.

    Google Scholar 

  18. Hershfield, M. S. and Kredich, N. M. (1978) S-adenosylhomocysteine hydrolase is an adenosine binding protein: A target for adenosine toxicity.Science 202:757–760.

    Google Scholar 

  19. Saebo, J. and Ueland, P. M. (1979) A study of the sequestration of adenosine and its conversion to adenine by the cyclic AMP-adenosine binding protein/S-adenosylhomocysteinase from mouse liver.Biochim. Biophys. Acta 587:333–340.

    Google Scholar 

  20. Palmer, J. L. and Abeles, R. H. (1979) The mechanism of action of S-adenosylhomocysteinase.J. Biol. Chem. 254:175–184.

    Google Scholar 

  21. Chiang, P. K., Guranowski, A. and Segall, J. E. (1981) Irreversible inhibition of S-adenosylhomocysteine hydrolase by nucleoside analogues.Arch. Biochem. Biophys. 207:175–184.

    Google Scholar 

  22. Bartlett, G. R. (1980) Metabolism of adenosine and deoxyadenosine by stored human red cells.Adv. Exp. Med. Biol. 122A:409–414.

    Google Scholar 

  23. Ueland, P. M. (1982) S-adenosylhomocysteinase from mouse liver. Inactivation of the enzyme in the presence of metabolites.Int. J. Biochem. 14:207–213.

    Google Scholar 

  24. Prentice, H. G., Russell, N. H., Lee, N., Ganeshaguru, Blacklock, H., Piga, A., Smyth, J. F. and Hoffbrand, A. V. (1981) Therepeutic selectivity of and prediction of response to 2′-deoxycoformycin in acute leukaemia.Lancet 2:1250–1253.

    Google Scholar 

  25. Renshaw, J. and Harrap, K. R. (1986)In vivo inhibition of mouse liver methyltransferase enzymes following treatment with 2′-deoxycoformycin and 2′-deoxyadenosine.Adv. Exp. Med. Biol. 195B:673–675.

    Google Scholar 

  26. Aarbacke, J., Miura, G. A., Prytz, P. S., Bessesen, A., Slordal, L., Gordon, R. K. and Chiang, P. K. (1986) Induction of HL-60 cell differentiation by 3-deaza-(+−)aristeromycin, an inhibitor of S-adenosylhomocysteine hydrolase.Cancer Res. 46:5469–5472.

    Google Scholar 

  27. Bajaj, S., Insel, J., Quagliata, F., Hirshhorn, R. and Silber, R. Adenosine and adenosine analogues are more toxic to chronic lymphocytic leukaemia than to normal lymphocytes.Blood 1:75–80.

  28. Siaw, M. F. E. and Coleman, M. S. (1984)In vitro metabolism of deoxycoformycin in human T lymphoblastoid cells: phosphorylation of deoxycoformycin and incorporation into cellular DNA.J. Biol. Chem. 259:9426–9433.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simmonds, H.A., Fairbanks, L.D., Duley, J.A. et al. ATP formation from deoxyadenosine in human erythrocytes: Evidence for a hitherto unidentified route involving adenine and S-adenosylhomocysteine hydrolase. Biosci Rep 9, 75–85 (1989). https://doi.org/10.1007/BF01117513

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01117513

Key Words

Navigation