Skip to main content
SpringerLink
Log in

Mechanism of suckling-rat hypercholesteremia. II. Cholesterol biosynthesis and cholic acid turnover studies

  • Published:
Lipids

Abstract

Cholesterol biosynthesis from acetate-2-14C by the livers of suckling rats, which is known to be relatively slow, was increased 2–3-fold within 24 hours after severing the bile duct. Cholesterol synthesis by sham-operated litter mates showed no change under similar treatment. Mevalonate biosynthesis from acetate-2-14C in vitro by recombined liver microsomal supernatant (105,000×g) fractions from suckling rats also was only 10% of that of comparable recombined fractions from normal controls (young adult rats which were consuming colony diet). Activity was not improved by combining either the microsomal or supernatant fraction from suckling rat livers with the complementary fraction from normal adult livers. On the other hand, activity was restored to 100% when microsomes from livers of duct-served suckling rats were combined with the supernatant fraction from normal controls. Likewise, recombined liver fractions prepared from adult rats fed synthetic diets exhibited low activity for mevalonate biosynthesis. Activity was restored by bile duct cannulation, but inhibited when cholic acid was infused into the cannulated animal. Therefore, surgical procedures which interrupt the enterohepatic recirculation of bile components lead to a restoration of cholesterol biosynthesis and, at least in the adult animal where cannulation studies are practicable, this effect can be reversed readily by bile acid infusion.

A slow rate of fecal excretion of14C-cholic acid was observed in suckling rats and rats fed synthetic diets, apparently reflecting an efficient enterohepatic recirculation of bile salts. The data suggest that under these dietary conditions bile salt retention either directly or indirectly influences hepatic synthesis of cholesterol.

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

References

  1. Carroll, K. K., Can. J. Biochem.42, 79–86 (1964).

    Article  CAS  Google Scholar 

  2. Harris, R. A., J. E. MacNintch, and F. W. Quackenbush, J. Nutr.90, 40–46 (1966).

    PubMed  CAS  Google Scholar 

  3. Bizzi, A. E. Veneroni and S. Garattini, J. Atheroscler. Res.3, 121–128 (1963).

    Article  PubMed  CAS  Google Scholar 

  4. Quackenbush, F. W., and M. Pawlowski, J. Nutr.72, 196–202 (1960).

    PubMed  CAS  Google Scholar 

  5. Fimognari, G. M., and V. W. Rodwell, Science147, 1038 (1964).

    Article  Google Scholar 

  6. Lowry, O. H., N. J. Rosebrough, A. L. Farr and R. J. Randall, J. Biol. Chem.193, 265–275 (1951).

    PubMed  CAS  Google Scholar 

  7. Lynen, F., and M. Grassl, Z. Physiol. Chem.313, 291–295 (1959).

    Google Scholar 

  8. Rudney, H., J. Biol. Chem.227, 363–377 (1957).

    PubMed  CAS  Google Scholar 

  9. Schlenk, H., and J. L. Gellerman, Anal. Chem.32, 1412–1414 (1960).

    Article  CAS  Google Scholar 

  10. Busher, N. L. R., K. McGarrahan, F. Gould and A. V. Loud, J. Biol. Chem.234, 262–267 (1959).

    Google Scholar 

  11. Bucher, N. L. R., “Biosynthesis of Terpenes and Sterols,” Ciba Foundation Symposium on Biosynthesis of Terpenes and Sterols, edited by G. F. W. Wolstenholme and M. O'Conner, 1959, p. 46–61.

  12. Siperstein, M. D., and M. J. Guest, J. Clin. Invest39, 642–652 (1960).

    Article  PubMed  CAS  Google Scholar 

  13. Siperstein, M. D., and V. M. Fagan, in “Advances in Enzyme Regulation” 2, Vol. 2., edited by G. Weber, 1964, p. 249–264.

  14. Siperstein, M. D., and V. M. Fagan, J. Biol. Chem.241, 602–609 (1966).

    PubMed  CAS  Google Scholar 

  15. Migicovsky, B. B., Can. J. Biochem.42, 105–110 (1964).

    CAS  Google Scholar 

  16. Lupien, P. J., and B. B. Migicovsky, Can. J. Biochem.42, 179–185 (1964).

    Article  PubMed  CAS  Google Scholar 

  17. Myant, N. B., and H. A. Eder, J. Lipid Res.2, 363–368 (1961).

    CAS  Google Scholar 

  18. Frantz, I. D. Jr., H. S. Schneider and B. T. Hinkelman, J. Biol. Chem.206, 465–469 (1964).

    Google Scholar 

  19. Tomkins, G. M., H. Sheppard and I. L. Chaikoff, J. Biol. Chem.201, 137–141 (1963).

    Google Scholar 

  20. Bloomfield, D. K., Proc. Natl. Acad. Sci. U.S.50, 117–124 (1963).

    Article  CAS  Google Scholar 

  21. Fimognari, G. M., and V. W. Rodwell, Biochemistry4, 2036–2090 (1965).

    Article  Google Scholar 

  22. Beher, W. T., G. D. Baker, W. L. Anthony and M. E. Beher, Henry Ford Hosp. Med. Bull.9, 201–213 (1961).

    PubMed  CAS  Google Scholar 

  23. Siperstein, M. D., Am. J. Clin. Nutr.8, 645–650 (1960).

    CAS  Google Scholar 

  24. Portman, O. W., Am. J. Clin. Nutr.8, 462–470 (1960).

    PubMed  CAS  Google Scholar 

  25. Carroll, K. K., Can. J. Biochem.42, 71–78 (1964).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. R. A. Harris

    Present address: Institute for Enzyme Research, University of Wisconsin, Madison, Wisconsin

  2. C. L. Villemez Jr

    Present address: Department of Chemistry, University of Colorado, Boulder, Colorado

Authors and Affiliations

  1. Department of Biochemistry, Purdue University, Lafayette, Indiana

    R. A. Harris, E. R. Rivera, C. L. Villemez Jr & F. W. Quackenbush

Authors
  1. R. A. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. R. Rivera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. L. Villemez Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. W. Quackenbush
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Presented in part before Federation of American Societies for Experimental Biology, Fed. Proc.24, 1078, 1965 (abstract). and in part at the AOCS Meeting, Los Angeles, April 1966.

Journal Paper No.2835, Purdue University Agricultural Experiment Station.

About this article

Cite this article

Harris, R.A., Rivera, E.R., Villemez, C.L. et al. Mechanism of suckling-rat hypercholesteremia. II. Cholesterol biosynthesis and cholic acid turnover studies. Lipids 2, 137–142 (1967). https://doi.org/10.1007/BF02530913

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02530913

Keywords

Search

Navigation