Advertisement

The Use of Model-Based Compartmental Analysis to Study Vitamin A Metabolism in a Non-Steady State

  • Michael H. Green
  • Joanne Balmer Green
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 537)

Abstract

Over the past 20 years, we have collaborated with several laboratories in using mathematical modeling to describe and quantitate whole-body Vitamin A Metabolism in the rat. Steady state models have been developed for animals at different levels of vitamin A status (Green et al., 1985; Lewis et al., 1990; Green and Green, 1994a; Kelley and Green, 1998) and in response to other variables (Kelley et al., 1998; Jang et al., 2000; Kelley et al., 2000). Limited experimental and mathematical evidence (Green and Green, 1994b; Novotny et al., 1995; v Reinersdorff et al., 1998) suggests that there are many similarities in Vitamin A Metabolism between rats and humans. As discussed at the 5th Conference on Mathematical Modeling in Experimental Nutrition in 1994 (Green and Green, 1996), modeling studies have uniquely contributed to current understanding of whole-body Vitamin A Metabolism. In particular, interpretation of kinetic data has revealed previously unrecognized complexities in vitamin A dynamics that facilitate homeostatic control of plasma (and probably tissue) vitamin A levels.

Keywords

Steady State Model Retinyl Ester TCDD Exposure Plasma Retinol Plasma Tracer 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adams, W.R., Smith, J.E., and Green, M.H., 1995, Effects of N-(4-hydroxyphenyl)retinamide on Vitamin A Metabolism in rats, Proc. Soc. Exp. Biol. Med. 208:178–185.Google Scholar
  2. Berman, M., and Weiss, M.F., 1978, SAAM Manual, DHEW Publ. #78–180, U.S. Government Printing Office, Washington, DC.Google Scholar
  3. Blaner, W.S., and Olson, J.A., 1994, Retinol and retinoic acid metabolism, in: The Retinoids: Biology, Chemistry, and Medicine, 2nd edn., M.B. Sporn, A.B. Roberts, and D.S. Goodman, eds., Raven Press, New York.Google Scholar
  4. Blomhoff, R., Green, M.H., Green, J.B., Berg, T., and Norum, K.R., 1991, Vitamin A Metabolism: new perspectives on absorption, transport, and storage, Physiol Rev. 71:951–990.Google Scholar
  5. Green, M.H., Uhl, L., and Green, J.B., 1985, A multicompartmental model of vitamin A kinetics in rats with marginal liver vitamin A stores, J. Lipid Res. 26:806–818.Google Scholar
  6. Green, M.H., and Green, J.B., 1990a, Experimental and kinetic methods for studying vitamin A dynamics in vivo, Meth. Enzymol 190:304–317.CrossRefGoogle Scholar
  7. Green, M.H., and Green, J.B., 1990b, The application of compartmental analysis to research in nutrition, Ann. Rev. Nutr. 10:41–61.CrossRefGoogle Scholar
  8. Green, M.H., and Green, J.B., 1994a, Vitamin A intake and status influence retinol balance, utilization and dynamics in rats, J. Nutr. 124:2477–2485.Google Scholar
  9. Green, M.H., and Green, J.B., 1994b, Dynamics and control of plasma retinol, in: Vitamin A in Health and Disease, R. Blomhoff, ed., Marcel Dekker, New York.Google Scholar
  10. Green, M.H., and Green, J.B., 1996, Quantitative and conceptual contributions of mathematical modeling to current views on Vitamin A Metabolism, biochemistry, and nutrition, Adv. Food Nutr. Res. 40:3–24.CrossRefGoogle Scholar
  11. Jang, J.-T., Green, J.B., Beard, J.L., and Green, M.H., 2000, Kinetic analysis shows that iron deficiency decreases liver vitamin A mobilization in rats, J. Nutr. 130:1291–1296.Google Scholar
  12. Kelley, S.K., and Green, M.H., 1998, Plasma retinol is a major determinant of vitamin A utilization in rats, J. Nutr. 128:1767–1773.Google Scholar
  13. Kelley, S.K., Nilsson, C.B., Green, M.H., Green, J.B., and Håkansson, H., 1998, Use of model-based compartmental analysis to study effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on vitamin A kinetics in rats, Toxicol. Sci. 44:1– 13.Google Scholar
  14. Kelley, S.K., Nilsson, C.B., Green, M.H., Green, J.B., and Håkansson, H., 2000, Mobilization of vitamin A stores in rats after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin: a kinetic analysis, Toxicol. Sci. 55:478–484.CrossRefGoogle Scholar
  15. Landaw, E.M., and DiStefano III, J.J., 1984, Multiexponential, multicompartmental and noncompartmental modeling. II. Data analysis and statistical considerations, Am. J. Physiol. 246:R665–R677.Google Scholar
  16. Lewis, K.C., Green, M.H., Green, J.B., and Zech, L.A., 1990, Retinol metabolism in rats with low vitamin A status: a multicompartmental model, J. Lipid Res. 31:1535–1548.Google Scholar
  17. Novotny, J.A., Dueker, S.R., Zech, L.A., and Clifford, A.J., 1995, Compartmental analysis of the dynamics of Rcarotene metabolism in an adult volunteer, J. Lipid Res. 36.1825–1838.Google Scholar
  18. v Reinersdorff, D., Green, M.H., and Green, J.B., 1998, Development of a compartmental model describing the dynamics of Vitamin A Metabolism in men, in: Mathematical Modeling in Experimental Nutrition, A. J. Clifford and H.-J. Miiller, eds., Plenum Press, New York.Google Scholar
  19. Wastney, M.E., Patterson, B.H., Linares, O.A., Greif, P.C., and Boston, R.C., 1999, WinSAAM, in: Investigating Biological Systems Using Modeling: Strategies and Software, Academic Press, San Diego.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Michael H. Green
    • 1
  • Joanne Balmer Green
    • 1
  1. 1.Nutrition DepartmentPennsylvania State UniversityUniversity Park

Personalised recommendations