Molecular Mechanisms of Intestinal Transport of Calcium, Phosphate, and Magnesium

Many new insights into the molecular mechanisms of intestinal absorption of calcium, phosphate, and magnesium have been made over the past decade. These include the identification, cloning, and characterization of transmembrane proteins responsible for the absorption of all three of these nutrient molecules. The proteins identified for uptake of Ca2+ and Mg2+ across the apical membrane of enterocytes are members of the transient receptor potential (TRP) family of cation channels (TRPV6 for Ca2+ and TRPM6/7 heterotetramers for Mg2+), while intestinal Pi absorption across the apical membrane is now known to be mediated by a member of the sodium-phosphate cotransporter gene family (NaPi-IIb; SLC34A2). Additionally, in some cases, molecules responsible for movement of these molecules across the cellular cytoplasm (e.g., calbindins for Ca2+) and exit across the basolateral membranes (e.g., plasma membrane calcium ATPase [PMCA1b] and the Na+/Mg2+ exchanger) of intestinal epithelial cells have also been identified and extensively studied. With the discovery of these channels and transporters, we now have a much clearer picture of the molecular mechanisms involved in the transport of these crucial nutrient molecules. However, for all three of these molecules, transport proteins involved in transcellular uptake seem to be important only when intake levels are low, as at higher dietary intake levels, absorption occurs passively via still relatively obscure, paracellular transport pathways. Furthermore, additional information has shown that these transport processes are regulated by a number of physiological mediators, and that these effects are mediated by direct influences on the expression or activity of the identified transporters.