Intestinal epithelial calcium transport system

The intestinal epithelial calcium transport system is a multi-protein physiological pathway responsible for the absorption of dietary calcium from the intestinal lumen into the systemic circulation, a process vital for skeletal health and cellular signaling [3, 12]. It consists of two primary routes: a passive, non-saturable paracellular pathway and a highly regulated, saturable transcellular pathway [3, 9]. The transcellular pathway is the rate-limiting mechanism for calcium absorption and involves three key molecular components: the apical entry channel TRPV6, the intracellular transport protein calbindin-D9k, and the basolateral extrusion pump PMCA1b [3, 10, 11]. This system is primarily regulated by the vitamin D endocrine system, where the active metabolite calcitriol binds to the vitamin D receptor (VDR) to induce the expression of these transport proteins [3, 6, 11]. Dysregulation of this system is central to the pathogenesis of metabolic bone diseases such as osteoporosis, rickets, and osteomalacia, as well as secondary hyperparathyroidism in chronic kidney disease [9, 11]. Therapeutic modulation of the system is achieved through vitamin D analogs to enhance absorption or, more recently, through specific inhibitors of components like TRPV6 for conditions like hypercalcemia or certain cancers where the channel is overexpressed [11, 12].

Other names

Active intestinal calcium absorption systemTranscellular calcium transport pathwayVitamin D-dependent calcium transport systemIntestinal calcium absorption pathwayDuodenal calcium transport system

Vitamin D receptor (VDR) agonism, TRPV6 channel inhibition, and substrate supplementation.