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Orotic Acid pp 26-30 | Cite as

Inhibitors of the Orotate Pathway

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Abstract

The first known drug affecting the orotate pathway was 6-azauridine [245,246]. This analogue is phosphorylated to 6-azauridine 5′-monophosphate which acts as a competitive inhibitor of orotidylic acid decarboxylase [247]. Therapeutic use of 6-azauridine [248,249] is occasionally complicated by a pronounced crystalluria. Owing to the block of orotidylic acid decarboxylase, large amounts of orotidine and orotic acid are excreted in urine. After the infusion of 6-azauridine the excretion of orotic acid precedes orotidine and the former disappears more rapidly from the urine. Psoriatic patients on azaribine (triacetylated form of 6-azauridine given orally) excreted 0.2–1.3 g of orotic acid and orotidine per day [250].

Keywords

Barbituric Acid Psoriatic Patient Orotic Acid Phenethyl Alcohol Pyrimidine Synthesis 
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. 245.
    Škoda, J., Hess, V. F. and Šorm, F. Experientia, 13, 150 (1957)PubMedCrossRefGoogle Scholar
  2. 246.
    Škoda, J. Handb. Exp. Pharmacol., 38/2, 348 (1975)Google Scholar
  3. 247.
    Handschumacher, R. E. J. Biol. Chem., 235, 2917 (1960)PubMedGoogle Scholar
  4. 248.
    Handschumacher, R. E., Calabresi, P., Welch, A. D., Bono, V. H., Fallon, H. J. and Frei, E. Cancer Chemother. Rep. 21, 1 (1962)PubMedGoogle Scholar
  5. 249.
    Turner, R. W. and Calabresi, P. J. Invest. Dermatol., 43, 551 (1964)PubMedGoogle Scholar
  6. 250.
    Milstein, H. G., Cornell, R. C. and Stoughton, R. B. J. Invest. Dermatol., 61, 183 (1973)PubMedCrossRefGoogle Scholar
  7. 251.
    Vogler, W. R., Horwitz, S. and Groth, D. P. Cancer Res., 29, 1371 (1969)PubMedGoogle Scholar
  8. 252.
    Janeway, C. M. and Cha, S. Cancer Res., 37, 4382 (1977)PubMedGoogle Scholar
  9. 253.
    Čihák, A. Oncology, 30, 405 (1975)Google Scholar
  10. 254.
    Veselý, J. and Čihák, A. Pharmacol. Ther. Part A, 2, 813 (1978)Google Scholar
  11. 255.
    Hrodek, O. and Veselý, J. Neoplasma, 18, 493 (1971)PubMedGoogle Scholar
  12. 256.
    Karon, M., Sieger, L., Leimbrock, S., Finklestein, J. Z., Nesbit, M. E. and Swaney, J. Blood, 42, 359 (1973)PubMedGoogle Scholar
  13. 257.
    Veselý, J., Čihák, A. and Šorm, F. Biochem. Pharmacol., 17, 519 (1968)PubMedCrossRefGoogle Scholar
  14. 258.
    Čihák, A. and Broucek, J. Biochem. Pharmacol., 21, 2497 (1972)PubMedCrossRefGoogle Scholar
  15. 259.
    Čihák, A., Veselý, J. and Šorm, F. Collect. Czech. Chem. Commun., 38, 3944 (1973)Google Scholar
  16. 260.
    Korbová, L., Kohout, J. and Čihák, A. Arch. Int. Pharmacodyn. Ther., 209, 332 (1974)PubMedGoogle Scholar
  17. 261.
    Čihák, A. Eur. J. Biochem., 58, 3 (1975)PubMedCrossRefGoogle Scholar
  18. 262.
    Čihák, A., Korbová, L., Kohout, J. and Reutter, W. Neoplasma, 25, 317 (1978)PubMedGoogle Scholar
  19. 263.
    Chelbova, K. V., Golovinsky, E. V. and Hadjiolov, A. A. Biochem. Pharmacol., 19, 2785 (1970)PubMedCrossRefGoogle Scholar
  20. 264.
    Kanetti, J. J. and Golovinsky, E. V. Chem. Biol. Interact., 3, 421 (1971)CrossRefGoogle Scholar
  21. 265.
    Handschumacher, R. E., Škoda, J. and Šorm, F. Collect. Czech. Chem. Commun., 28, 2983 (1963)Google Scholar
  22. 266.
    Smith, D. A. and Visser, D. W. J. Biol. Chem., 240, 446 (1965)PubMedGoogle Scholar
  23. 267.
    Smith, D. A., Roy-Burman, P. and Visser, D. W. Biochim. Biophys. Acta, 119, 221 (1966)PubMedGoogle Scholar
  24. 268.
    Foster, D. M., Choy-Soong, L. and O’Sullivan, W. J. Biochem. Med. 7, 61 (1973)PubMedCrossRefGoogle Scholar
  25. 269.
    Stone, J. E. and Potter, V. R. Cancer Res., 17, 800 (1957)PubMedGoogle Scholar
  26. 270.
    Dahl, J. L., Way, J. L. and Parks, R. E. J. Biol. Chem., 234, 2998 (1959)PubMedGoogle Scholar
  27. 271.
    Čihák, A., Wilkinson, D. S. and Pitot, H. C. Adv. Enzyme Regul., 9, 267 (1971)CrossRefGoogle Scholar
  28. 272.
    Wilkinson, D. S., Čihák, A. and Pitot, H. C. J. Biol. Chem., 246, 6418 (1971)PubMedGoogle Scholar
  29. 273.
    Garrett, C. T., Wilkinson, D. S., Tweedle, J. W. and Pitot, H. C. Arch. Biochem. Biophys., 155, 342 (1973)PubMedCrossRefGoogle Scholar
  30. 274.
    Granat, P., Creasey, W. A., Calabresi, P. and Handschumacher, R. E. Clin. Pharmacol. Ther., 6, 436 (1965)PubMedGoogle Scholar
  31. 275.
    Handschumacher, R. E. Cancer Res., 23, 634 (1963)PubMedGoogle Scholar
  32. 276.
    Čihák, A. and áorm, F. Biochim. Biophys. Acta, 149, 314 (1967)PubMedGoogle Scholar
  33. 277.
    Rubin, R. J., Reynard, A. and Handschumacher, R. E. Cancer Res., 24, 1002 (1964)PubMedGoogle Scholar
  34. 278.
    Čihák, A. and Šorm, F. Collect. Czech. Chem. Commun., 33, 1778 (1968)Google Scholar
  35. 279.
    Čihák, A. and Šorm, F. Biochem. Pharmacol., 21, 607 (1972)PubMedCrossRefGoogle Scholar
  36. 280.
    Hatfield, P. J., Simmonds, H. A., Cameron, J. S., Jones, A. S. and Cadenhead, A. Adv. Exp. Med. Biol., 41, 637 (1974)PubMedGoogle Scholar
  37. 281.
    Santilli, V., Škoda, J., Gut, J. and Šorm, F. Biochim. Biophys. Acta, 155, 623 (1968)PubMedGoogle Scholar
  38. 282.
    Mardashev, S. R. and Fitzner, A. B. Vopr. Med. Khim., 13, 303 (1967)PubMedGoogle Scholar
  39. 283.
    Mandel, H. G., Triester, S. R. and Szapary, D. Biochem. Pharmacol., 19, 1879 (1970)PubMedCrossRefGoogle Scholar
  40. 284.
    Fitzner, A. B. Vopr. Med. Khim., 15, 465 (1969)Google Scholar
  41. 285.
    Fitzner, A. B. and Mardashev, S. R. Vopr. Med. Khim. 16, 99 (1970)Google Scholar
  42. 286.
    Mandel, H. G., Oliver, H. M. and Riis, M. Mol. Pharmacol., 3, 537 (1967)PubMedGoogle Scholar
  43. 287.
    Mandel, H. G. and Riis, M. Biochem. Pharmacol., 19, 1867 (1970)PubMedCrossRefGoogle Scholar
  44. 288.
    Seifert, J. and Vácha, J. Mol. Pharmacol., 9, 259 (1973)PubMedGoogle Scholar
  45. 289.
    Seifert, J. and Vácha, J. Drug Metab. Dispos., 3, 430 (1975)PubMedGoogle Scholar

Copyright information

© A. Čihák and W. Reutter 1980

Authors and Affiliations

  1. 1.Institute of Organic Chemistry and BiochemistryCzechoslovakia Academy of Sciences PragueCzechoslovakia
  2. 2.Institut für Molekularbiologie und Biochemie der Freien UniversitätBerlinGermany

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