CALCIUM AND MAGNESIUM HOMEOSTASIS

12.2 CALCIUM AND MAGNESIUM HOMEOSTASIS

Calcium is present in abundant amounts in various body pools, with both bone and teeth containing approximately 99% of total body calcium in forms of calcium

phosphate salt or hydroxyapatite crystal (Ca 10 (PO 4 ) 6 (OH) 2 ). The remaining 1% of calcium ion is present in blood, muscle, and extra- and intracellular fluids and has

a critical role in nerve transmission, muscle contraction, and blood-clotting mech- anisms. Magnesium is the second most abundant intracellular cation, with approx- imately half present in soft tissue and the other half found in bone. Both calcium and magnesium concentrations are maintained in a relatively narrow range in both

extra- and intracellular compartments. 13 Calcium and magnesium homeostasis is regulated by three principal organ systems: the intestine, skeleton, and kidney. The intestine represents the sole port of entry of calcium and magnesium into the body and contributes significantly to mineral homeostasis by influencing both absorption and secretion activities (Table 12.1). The processes of intestinal calcium transport involve essentially a transmucosal transport, with the mucosal layer of the intestine representing the only barrier that calcium ions have to cross to reach the portal circulation. Thus, calcium movements from the intestinal lumen into the circulation, or from various body pools into the intestinal lumen, represent calcium transport. The rate of intestinal calcium transport, when plotted against

the concentration of intraluminal calcium, gives a curvilinear fit, 14 indicating that

Carbohydrates and Mineral Metabolism

TABLE 12.1 Calcium Transport Mechanisms across Intestinal Barrier

Intestinal Transport Mechanism Feature

Cellular

Paracellular

Intestinal compartment Cytosolic component of Extracellular space between

enterocytes Active components

enterocyte

Sequestering by vitamin D- Simple diffusion or osmotic

dependent, Ca binding proteins,

properties between tight

facilitated diffusion, or

junctions of adjacent enterocytes

endocytosis

Regulation factors Plasma mineral concentration, Presence of soluble mineral, co- 1,25 (OH) 2 D 3 nutrient (lactose)-induced generation of osmotic gradient

two process components — saturable and nonsaturable mechanisms — exist for the transport process. The two biochemical aspects that define the transport of

calcium across the intestinal barrier involve both a cellular (e.g., facilitated) pathway, characterized by the involvement of biosynthesized and active proteins, and a paracellular (e.g., passive) pathway. With the cellular transport, calcium ions move into the absorption cell cytosolic compartment of the mucosal lining of the small intestine (e.g., enterocyte) by four coordinated steps. First, calcium enters into the cytosol via the apical membrane and is moved from the membrane to the basolateral membrane of the enterocyte before calcium extrusion takes place at the basolaeral membrane into the lateral space occupied by the lamina propria. From the lateral space, calcium diffuses into the portal circulation. To accomplish this process, the calcium ion must enter the enterocyte by diffusion or by binding

to the apical membrane cytoskeletal proteins. 15 From here, the divalent ion is sequestered by vitamin D-dependent calcium binding proteins, calbindin (e.g., –9k in the rat, 32k in the chicken), or transported to the basolateral membrane by a

facilitated diffusion. 16 Calcium is extruded into the lateral space by a calcium extrusion pump, which involves a transmembrane protein associated with the basolateral membrane. 17 Since the cellular pathway for both calcium and magne- sium transport requires metabolic energy, it is considered an active, energy-requir- ing process. 18 Calcium and magnesium have been shown to produce an antagonistic effect on respective absorption. Classic in vitro experiments, using the inverted gut sac technique, have shown that magnesium and calcium compete with each

other for intestinal absorption. 19 For example, feeding calcium supplements con- taining magnesium to rats resulted in a poorer absorption of calcium from the supplement than did control animals fed milk. 20 In human studies, the ingestion of excess calcium reduces intestinal absorption of magnesium. 21 Paracellular uptake of calcium and magnesium in the intestine occurs by simple diffusion of the ion. Since mechanisms for both calcium and magnesium involve in part passive diffusion, the osmotic properties of the intestinal contents will influence the extent of absorption. A solvent drag effect occurs that involves the movement of soluble calcium ions from the intestinal lumen into the lateral space. The osmotic

Functional Food Carbohydrates

gradient developed between the lateral space and the intestinal lumen occurs by active extrusion of sodium and chloride ions into the lateral space. In the case of calcium, there is no apparent regulatory control for this mode of transport of calcium, albeit

extracellular calcium is involved in the formation of tight junctions 22 and intracellular calcium has an important role for maintaining the integrity of the tight junctions. 23 Thus, calcium may modulate paracellular transport directly by influencing gap junction structure and function. Intestinal absorption of magnesium also occurs mainly in the distal parts of the intestine, such as the jejenum and the ileum, where passive diffusion

contributes to a major portion of absorption. 24 Some of the more prominent co- nutrients, or digestion products that stimulate calcium transport, are lactose, 25 casein phosphopeptides, 26,27 bile salts, and some amino acids. 28,29 Some fats may also impair calcium bioavailability by forming insoluble soaps with the free ion, and sodium intake can also lead to increased urinary calcium loss and potential effects on bone density. Since bioavailability is influenced by so many factors, including absorption, transport, cellular organization, storage, and excretion of the nutrient, an absolute definition of the term bioavailability of calcium or magnesium is required when assessing the effect

of different dietary constituents on absorption and utilization of this mineral. 26 To complicate matters, the complexity of the system likely makes a single method to evaluate calcium bioavailability unsatisfactory.