Abstract
Compartmental modeling is a useful tool for investigating metabolic systems and processes. We and others have applied it to the study of zinc metabolism in humans. Because existing models could not be accurately fitted to our data, we have developed a new model of human zinc metabolism based on stable isotope tracer data from studies of five healthy adults. Multiple isotope tracers were administered orally and intravenously and the resulting enrichment measurement in plasma, erythrocytes, urine, and feces. These tracer kinetic data, along with other measured and calculated tracee and steady-state data, were used to develop the model. A single model structure composed of fourteen compartments was found to be suitable for all subjects. Model development and fitting of data and model for each subject were accomplished using the SAAM/CONSAM computer programs. The model development and fitting processes are described and exemplified using data from one of the subjects. While identifiability could not be demonstrated a priori due to the model’s complexity, parameter statistics for the fitted models did show most parameters to be adequately identified a posteriori.
Keywords
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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Berman M; Weiss MF. user’s Manual for SAAM. US Department of Health, Education, and Welfare, Publication No. (NIH) 78–180, Washington, DC. 1978.
Berman M. A deconvolution scheme. Math Biosci, 1978, 40:319–323.
Berman M. Kinetic analysis and modeling: theory and applications to lipoproteins, in: Lipoprotein Kinetics and Modeling. Berman M; Grundy SM; Howard BV; Eds. Academic Press: New York. 1982. pp. 3–36.
Berman M; Beltz WF; Greif PC; Chabay R; Boston RC. CONSAM User’s Guide. US Department of Health and Human Services, Washington, DC. 1983.
Boston R; Lyne A; McNabb T; Pettigrew K; Greif P; Ramberg C; Zech L. Kinetic models to describe populations: A strategy for summarizing the results of multiple studies, in: Kinetic Models of Trace Element and Mineral Metabolism During Development. Siva Subramanian KN; Wastney ME; Eds. CRC Press: Boca Raton, FL. 1995. pp. 359–372.
Carson ER; Cobelli C; Finkelstein L. The Mathematical Modeling of Metabolic and Endocrine Systems. John Wiley & Sons: New York. 1983.
Cobelli C; Lepschy A; Jacur GR. Identifiability of compartmental systems and related structural properties. Math Biosci, 1979, 44:1–18.
Cobelli C; DiStefano JJ III. Parameter and structural identifiability concepts and ambiguities: A critical review and analysis. Am J Physiol, 1980, 239 (Regulatory Integrative Comp Physiol 8):R7–R24.
Cobelli C. Compartmental models: Theory and practices using the SAAM II software system. In this volume. CONSAM User’s Manual. Resource Facility for Kinetic Analysis: Seattle. 1990.
Cousins RJ. Absorption, transport, and hepatic metabolism of copper and zinc: Special reference to metallothionein and ceruloplasmin. Physiol Rev, 1985, 65:238–309.
Cousins RJ. Systemic transport of zinc, in: Zinc in Human Biology. Mills CF; Ed. Springer-Verlag: London. 1989. pp. 79–93.
DiStefano JJ III. Complete parameter bounds and quasi-identifiability conditions for a class of unidentifiable linear systems. Math Biosci, 1983, 65:51–68.
Fairweather Tait SJ; Jackson ML; Fox TE; Wharf SG; Eagles J; Croghan PC. The measurement of exchangeable pools of zinc using the stable isotope 70Zn. Br J Nutr, 1993, 70:221–234.
Foster DM; Aamodt RL; Henkin RI; Berman M. Zinc metabolism in humans: A kinetic model. Am J Physiol, 1979, 237(5):R340–349.
Foster DM; Boston RC; Jacquez JA; Zech LA. The SAAM Tutorials: An Introduction to using Conversational SAAM Version 30. Resource Facility for Kinetic Analysis: Seattle. 1989.
Friel JK; Naake VL; Miller LV; Fennessesy PV; and Hambidge KM. The analysis of stable isotopes in urine to determine the fractional absorption of zinc. Am J Clin Nutr, 1992, 55:473–477.
Geigy Scientific Tables, 8th Ed. Lentner C; Ed. Ciba-Geigy Corporation: West Caldwell, New Jersey. 1984.
Godfrey KR; DiStefano JJ III. Identifiability of model parameters, in: Identifiability of Parametric Models. Walter E; Ed. Pergamon Press: Oxford. 1987.
Jacquez JA. Compartmental Analysis in Biology and Medicine. University of Michigan Press: Ann Arbor. 1985.
Jacquez JA; Perry T. Parameter estimation: local identifiability of parameters. Am J Physiol, 1990, 258 (Endocrinol Metab 21):E727–E736.
Jackson ML; Jones DA; Edwards RHT; Swainbank IG; Coleman ML. Zinc homeostasis in man: Studies using a new stable isotope-dilution technique. Br J Nutr, 1984, 51:199–208.
Jackson ML. Physiology of zinc: general aspects, in: Zinc in Human Biology. Mills CF; Ed. Springer-Verlag: London. 1989. pp. 1–14.
Krebs NF; Miller LV; Naake VL; Lei S; Westcott JE; Fennessey PV; Hambidge KM. The use of stable isotope techniques to assess zinc metabolism. J Nutr Biochem, 1995, 6:292–301.
Lönnerdal B. Intestinal absorption of zinc, in: Zinc in Human Biology. Mills CF; Ed. Springer-Verlag: London. 1989. pp. 33–55.
Lowe NM; Green A; Rhodes JM; Lombard M; Jalan R; Jackson ML. Studies of human zinc kinetics using the stable isotope 70Zn. Clin Sci, 1993, 84:113–117.
Lowe NM; Shames DM; Woodhouse LR; Matel JS; Roehl R; Saccomani MP; Toffolo G; Cobelli C; King JC. A compartmental model of zinc metabolism in healthy women using oral and intravenous stable isotope tracers. Am J Clin Nutr, 1997,65:1810–1819.
Lyne A; Boston R; Pettigrew K; Zech L. EMSA: A SAAM service for the estimation of population parameters based on model fits to identically replicated experiments. Comput Methods Prog Biomed, 1992, 38:117–151.
Miller LV; Hambidge KM; Naake VL; Hong Z; Westcott JL;. Fennessey PV. Size of the zinc pools that exchange rapidly with plasma zinc in humans: Alternative techniques for measuring and relation to dietary zinc intake. J Nutr, 1994, 124:268–276.
Novotny JA; Zech LA; Furr HC; Dueker SR; Clifford AJ. Mathematical modeling in nutrition: Constructing a physiologic compartmental model of the dynamics of β-carotene metabolism, in: Advances in Food and Nutrition Research, Vol. 40, Mathematical Modeling in Experimental Nutrition: Vitamins, Proteins, Methods. Coburn SP; Townsend DW. Eds. Academic Press: San Diego. 1996. pp. 25–54.
Shipley RA; Clark RE. Tracer Methods for In Vivo Kinetics. Academic Press: New York. 1972.
Van Dokkum W; Fairweather-Tait SJ; Hurrell R; Sandström B. Study techniques, in: Stable Isotopes in Human Nutrition: Inorganic Nutrient Metabolism. Mellon F; Sandström B; Eds. Academic Press: London. 1996. pp. 23–42.
Van Wouwe JP; Veldhuizen M; De Goeij JJM; Van den Hamer CJA. In vitro exchangeable erythrocytic zinc. Biol Trace Element Res, 1990, 25:57–69.
Walter E; Ed. Identifiability of Parametric Models. Pergamon Press: Oxford. 1987.
Wastney ME; Aamodt RL; Rumble WF; Henkin RI. Kinetic analysis of zinc metabolism and its regulation in normal humans. Am J Physiol, 1986, 251 (Regulatory Integrative Comp Physiol 20):R398–R408.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Miller, L.V., Krebs, N.F., Hambidge, K.M. (1998). Human Zinc Metabolism: Advances in the Modeling of Stable Isotope Data. In: Clifford, A.J., Müller, HG. (eds) Mathematical Modeling in Experimental Nutrition. Advances in Experimental Medicine and Biology, vol 445. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1959-5_16
Download citation
DOI: https://doi.org/10.1007/978-1-4899-1959-5_16
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-1961-8
Online ISBN: 978-1-4899-1959-5
eBook Packages: Springer Book Archive