Zinc and Gastrointestinal Disorders: A Role for the Zinc Transporters Zips and ZnTs

Background: Zinc is a critical metal ion essential for life. The biological significance of zinc is highlighted by the enormous number of proteins ( approximately 10% of the human proteome) that have zinc- binding capacity. Accordingly, zinc concentrations in cells are tightly regulated by two families of zinc transporter proteins: Slc30a ( ZnT) and Slc39a ( Zip). ZnT and Zip are known to decrease and increase cytosolic zinc concentrations respectively. Both zinc transporters are suggested to be implicated in a number of disorders and disease states through dysfunctional zinc transport including cancer, diabetes and gastrointestinal ( GI) disease. Method: The goal of this work was to identify the role of zinc transporters in GI disease/disorders. Where possible, reference will be made in the context of the function of zinc transporters and their potential role in GI disorders/diseases with a view towards their possible therapeutic utility in the treatment of these ailments. PubMed was utilized to search for articles with the terms "zinc and GI disease", "zinc transporters and GI disease", "zinc and gut", zinc transporters and gut", and "zinc transporters and intestinal disorders". Results: We identified a number of reviews on GI disorders/disease states associated with zinc deficiencies, but the very proteins that transport this metal ion in these systems are not well-defined. From a systematic review, we identified the following zinc transporters (Zip1, 2, 4-7, 10, 11 and 14; and ZnT1, 8 and 10) as having some functional role in the GI system and potentially could have a therapeutic role in the treatment of GI disease/disorders. Conclusion: An increasingly common health issue in our communities is disorder/disease of the GI system. Although therapies targeting these disorders are somewhat beneficial, there is a need to develop better, more efficient treatments. Despite that many gut-related disorders/disease states have been analyzed in the context of zinc deficiencies, the transport proteins that move zinc across cells are not well-defined. Zinc transporters are expressed in a range of GI tissue and cells, and their roles in the maintenance, integrity and disease processes of the GI system need to be addressed. This might open a whole new avenue of opportunities for the development of novel therapies targeting these receptors in GI disease states.