Figure 512

Proposed pathways for calcium (Ca) absorption across the intestinal epithelium. Two routes exist for the absorption of Ca across the intestinal epithelium: the paracellular pathway and the transcellular route. The paracellular pathway is passive, and it is the predominant means of Ca absorption when the luminal concentration of Ca is high. This is a nonsaturable pathway and can account for one half to two thirds of total intestinal Ca absorption. The paracellular absorptive route may be indirectly influenced by 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) because it may be capable of altering the structure of intercellular tight junctions by way of activation of protein kinase C, making the tight junction more permeable to the movement of Ca. However, 1,25(OH)2D3 primarily controls the active absorption of Ca. (1) Ca moves down its concentration gradient through a Ca channel or Ca transporter into the apical section of the microvillae. Because the intestinal concentration of Ca usually is 10-3 mol and the intracellular Ca concentration is 10-6 mol, a large concentration gradient favors the passive movement of Ca. Ca is rapidly and reversibly bound to the calmodulin-actin-myosin I complex. Ca may then move to the basolateral area of the cell by way of microvesicular transport, or ionized Ca may diffuse to this area of the cell. (2) As the calmod-ulin complex becomes saturated with Ca, the concentration gradient for the movement of Ca into the microvillae is not as favorable, which slows Ca absorption. (3) Under the influence of calcitriol, intestinal epithelial cells increase their synthesis of calbindin. (4) Ca binds to calbindin, thereby unloading the Ca-calmodulin complexes, which then remove Ca from the microvillae region. This decrease in Ca concentration again favors the movement of Ca into the microvil-lae. As the calbindin-Ca complex dissociates, the free intracellular Ca is actively extruded from the cell by either the Ca-adenosine triphos-phatase (ATPase) or Na-Ca exchanger. Calcitriol may also increase the synthesis of the plasma membrane Ca-ATPase, thereby aiding in the active extrusion of Ca into the lamina propria [2,7,9,17,18].

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