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Center for Nutritional Sciences, University of Florida, Gainesville, FL 32611
Dietary zinc may regulate zinc absorption in part via the inhibitory effect of intestinal metallothionein, but the mechanism is unknown. We recently showed that cysteine-rich intestinal protein (CRIP) binds zinc during transmucosal zinc transport, and that CRIP may function as an intracellular zinc carrier. The present experiments examine the interaction of CRIP and metallothionein with zinc to evaluate their potential roles in the mechanism of zinc absorption. Intestinal metallothionein concentrations were lower and zinc absorption rates from isolated intestinal loops were higher in rats fed a low zinc diet compared with those fed a high zinc diet or given parenteral zinc to induce metallothionein synthesis. Zinc status did not affect the apparent CRIP concentration, but markedly altered the distribution of 65Zn in intestinal cytosol as determined by gel filtration HPLC. More 65Zn was associated with CRIP (40 vs. 14%) and less was bound to metallothionein (4 vs. 5259%) in rats fed the low zinc diet compared with rats of high zinc status. Luminal zinc concentration also affected the distribution of 65Zn in the cytosol. CRIP bound progressively less (from 42 to 25%) of the 65Zn taken up from the lumen as the luminal zinc concentration was increased from 5 to 300 µmol/L. Collectively these data suggest that CRIP is a saturable, intracellular zinc transport protein, and that metallothionein inhibits zinc absorption by binding zinc in competition with CRIP. A hypothetical model for the mechanism of transcellular zinc absorption involving metallothionein and CRIP is presented and discussed.
KEY WORDS: transport metalloproteins trace elements zinc rats
1 Supported by National Institutes of Health Grant No. DK31127 (to RJC) and National Research Service Award DK08276 (to JMH) from the National Institute of Diabetes and Digestive and Kidney Diseases, and Boston Family Endowment Funds.
2 Present address: Department of Pediatrics, Louisiana State University School of Medicine, New Orleans, LA 70112.
3 To whom correspondence and reprint requests should be addressed.
Manuscript received 20 September 1991. Revision accepted 28 October 1991.
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