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Journal of Nutrition Vol. 124 No. 4 April 1994, pp. 580-587
Copyright © 1994 by American Society for Nutrition
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Inositol Phosphates Inhibit Uptake and Transport of Iron and Zinc by a Human Intestinal Cell Line1,2,3,

Okhee Han, Mark L. Failla4, A. David Hill*, Eugene R. Morris* and J. Cecil Smith, Jr.*

Department of Food, Nutrition and Food Service Management, The University of North Carolina, Greensboro, NC 27412 * Vitamin and Mineral Nutrition Laboratory, Beltsville Human Nutrition Research Center, Agriculture Research Service, U.S. Department of Agriculture, Beltsville, MD 20705

To examine the influence of inositol phosphates on the uptake and absorption of Fe and Zn, Caco-2 cells were grown on either plastic (uptake studies) or porous membranes in bicameral chambers (transport/absorption studies). Caco-2, a human colon adenocarcinoma cell line, was selected as the test cell because it spontaneously differentiates into polarized enterocyte-like cells at confluency. Uptake of Fe (added as Fenitrilotriacetate complex) from a calcium-free solution by fully differentiated cells was 37 pmol/cm2. Addition of 10-fold molar excess of individual inositol phosphates (IP3, IP4, IP5 or IP6) decreased Fe solubility by 13 to 25% and reduced Fe uptake by 50 to 65%. The rate of transport of Fe from the apical solution into the basolateral chamber [1.4 ± 0.1 pmol/(h·cm2)] decreased (34–96%) in proportion to the degree of phosphorylation of the inositol derivative in the apical compartment. Uptake and transepithelial transport of Zn were 246 ± 5 pmol/cm2 and 23 ± 1 pmol/(h·cm2), respectively. The solubility, uptake and rate of transport of Zn also decreased in proportion to the degree of phosphorylation of inositol. These results demonstrate the inhibitory influence of IP3–IP6 on the uptake and transport of Fe and Zn and support the usefulness of the Caco-2 human cell line as an appropriate model for evaluating the effects of specific dietary factors on trace metal bioavailability.


KEY WORDS: • trace metals • bioavailability • absorption • phytate • Caco-2 human cells

1 Presented in part at Experimental Biology 93, March 28–April 1, 1993, New Orleans, LA [Hill, A. D., Han, O., Failla, M. L., Hopkins, R., Morris, E. R. & Smith, J. C. (1993) Caco-2 cells as a model for studying mineral bioavailability: effects of inositol phosphates on the absorption of iron and zinc. FASEB J. 7: A306 (abs.)].

2 Supported in part by North Carolina Agriculture Experiment Station.

3 The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

4 To whom correspondence should be addressed.

Manuscript received 4 August 1993. Revision accepted 29 October 1993.




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