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Selective Inhibition of Hepatic but Not Intestinal β-Lipoprotein Production and Triglyceride Transport in Rats Given Orotic Acid

  • H. G. Windmueller
  • R. I. Levy
  • Albert E. Spaeth
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 4)

Abstract

Orotic acid (l,2,3,6-tetrahydro-2,6 dioxo-4-pyrimidinecarboxylic acid; uracil-4-carboxylic acid), synthesized by mammalian cells from aspartic acid and carbamyl phosphate, is an intermediate in the pathway leading to the biosynthesis of pyrimidine nucleotides (1). Animals have no nutritional requirement for orotic acid. Its intracellular concentration is very low, since In the presence of ribosylpyrophosphate 5-phosphate (PP-ribose-P) it is efficiently converted to the nucleotide, orotidylic acid (2), which in turn is decarboxylated to uridylic acid, or UMP. UMP is a precursor for all other cellular pyrimidine nucleotides.

Keywords

Fatty Liver Orotic Acid Plasma Lipid Concentration Carbamyl Phosphate Intestinal Lymph 
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.
    Arvidson, H., Eliasson, N. A., Hammarsten, E., Reichard, F. and von Ubisch, H. J. Biol. Chem. 179:169 (1949).PubMedGoogle Scholar
  2. 2.
    Romberg, A., Lieberman, I. and Siraras, E. S. J. Siol. Chem. 215:389 (1955).Google Scholar
  3. 3.
    Standerfer, S. B. and Handler, P. Froc. Soc. Exptl. Biol. Med. 90:270 (1955).Google Scholar
  4. 4.
    Handschumacher, R. E., Creasey, W. A., Jaffe, J. J., Pasternak, C. A. and Hankin, L. Proc. Natl. Acad. Sci. U.S. 46:178 (1960).CrossRefGoogle Scholar
  5. 5.
    Hayano, K., Tsubone, I., Asuma, X. and Yamamura, Y. J. Biochem. (Tokyo) 52:379 (1962).Google Scholar
  6. 6.
    Novikoff, A. B., Roheim, P. S. and Quintana, N. Lab. Invest. 15:27 (1966).Google Scholar
  7. 7.
    Jatlow, P., Adams, W. R. and Handschumacher, R, E. Am. J. Pathol. 47:125 (1965).Google Scholar
  8. 8.
    Creasey, W. A., Hankin, L. and Handschumacher, R. E. J. Biol. Chem. 236:2064 (1961).PubMedGoogle Scholar
  9. 9.
    Rajalakshmi, S., Sarma, D. S. R. and Sarma, P. Biochem, J. 80:375 (1961).Google Scholar
  10. 10.
    Windmueller, H. G. J. Biol. Chem. 239:530 (1964).PubMedGoogle Scholar
  11. 11.
    Sidransky, H. and Verney, E. Ara. J. Pathol. 46:1007 (1965).Google Scholar
  12. 12.
    Windmueller, H. 6. Unpublished observations.Google Scholar
  13. 13.
    Hallanger, L. E., Laakso, J. W. and Schultze, H. O. J. Biol. Chem. 202:83 (1953).PubMedGoogle Scholar
  14. 14.
    Windmueller, H. G. J. Hutr. 85:221 (1965).Google Scholar
  15. 15.
    Windmueller, H. G. Biochem. Biophys. Res. Commun. 11:496 (1963).PubMedCrossRefGoogle Scholar
  16. 16.
    Windmueller, H. G. and Levy, R. I. J. Biol. Chem. 242:2246 (1967).PubMedGoogle Scholar
  17. 17.
    Gotto, A. M., Levy, R. I., Rosenthal, A. S., Birnbaumer, M. E. and Fredrickson, D. S. Biochem. Biophys. Res. Communs. 31:699 (1968).CrossRefGoogle Scholar
  18. 18.
    Klain, G. J. and Whitten, B. K. Biochira. Biophys. Acta 144:174 (1967).Google Scholar
  19. 19.
    Windmueller, H. G. and Spaeth, A. E. J. Biol. Chem. 241:2891 (1966).PubMedGoogle Scholar
  20. 20.
    Rubin, R. J. and Pendleton, R. G. Federation Proc. 23:126 (1964).Google Scholar
  21. 21.
    Windmueller, H. G. and Spaeth, A. E. J. Biol. Chem. 240:4398 (1965).PubMedGoogle Scholar
  22. 22.
    Roheim, P. S., Switzer, S., Girard, A. and Eder, H. A. Biochem. Biophys. Res. Communs. 20:416 (1965).CrossRefGoogle Scholar
  23. 23.
    Deamer, D. W., Kruger, F. A. and Cornuell, D. G. Biochim. Biophys. Acta 97:147 (1965).PubMedCrossRefGoogle Scholar
  24. 24.
    Farquhar, J. W. and Ways, P., in J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson (Editors), “The Metabolic Basis for Inherited Disease,” McGraw-Hill Book Co., New York, 1966, p.509.Google Scholar
  25. 25.
    Isselbacher, K. J., Scheig, R., Plotkin, G. R. and Caulfield, J. B. Medicine (Baltimore), 43:347 (1964).Google Scholar
  26. 26.
    Levy, R. I., Fredrickson, D. S. and Laster, L. J. Clin. Invest. 45:531 (1966).PubMedCrossRefGoogle Scholar
  27. 27.
    Windmueller, H. G. and Levy, R. I. J. Biol. Chem. 243:4878 (1968).PubMedGoogle Scholar
  28. 28.
    Zilversmit, D. B., Sisco, P. H. and Yokoyama, A. Biochim. Biophys. Acta 125:129 (1966).PubMedGoogle Scholar
  29. 29.
    Von Etiler, L. H, Rubin, R J, and Handschumacher, R. E. J. Biol. Chem. 238:2464 (1963).Google Scholar
  30. 30.
    Marchetti, M., Puddu, P. and Caldarera, C. M. Biochim. Biophys. Acta 61:826 (1962).PubMedGoogle Scholar
  31. 31.
    Bresnick, E., Mayfield, E. D., Jr. and Mosse, H. Mol. Pharmacol. 4:173 (1968).PubMedGoogle Scholar
  32. 32.
    Windmueller, H. G., McDaniel, E. G. and Spaeth, A. Arch. Biochem. Biophys. 109:13 (1965).PubMedCrossRefGoogle Scholar
  33. 33.
    Hurlbert, R. B. and Potter, V. R. J. Biol. Chem. 195:257 (1952).Google Scholar
  34. 34.
    Von Euler, L. H. and Windmueller, H. G. Proc. Soc. Exptl. Biol. Med. 125:1251 (1967).Google Scholar
  35. 35.
    Von Euler, L. H. and Windmueller, H. G. Unpublished observations.Google Scholar
  36. 36.
    Sidransky, H., Verney, E. and Lombard!, B. J. Nutrition 81: 348 (1963).Google Scholar
  37. 37.
    Kobata, A., Furuno, K. and Ziro, S. J. Biochem. (Tokyo) 55:92 (1964).Google Scholar
  38. 38.
    Sidransky, H. Endocrinology 77:709 (1963).CrossRefGoogle Scholar
  39. 39.
    Kelley, W. H., Rosenbloora, F. M., Levy, R. I. and Seegmiller, J. E. (In preparation).Google Scholar

Copyright information

© Pleum Press 1969

Authors and Affiliations

  • H. G. Windmueller
    • 1
  • R. I. Levy
    • 2
  • Albert E. Spaeth
    • 1
  1. 1.National Institute of Arthritis and Metabolic DiseasesBethesdaUSA
  2. 2.National Heart InstituteBethesdaUSA

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