Mineral regulation of vitamin D metabolism

The pediatrician's interest in vitamin D metabolism stems from the once-endemic rachitic deformities induced by vitamin D deficiency; later, clinical research of inherited forms of rickets established further principles of vitamin D metabolism and action. Constantine Anast, as both clinician and researcher, maintained an enthusiastic interest in vitamin D metabolism. His investigative esprit fostered my interest, as a fellow in his laboratory, in the synthetic pathway of active vitamin D.The best known active metabolite of vitamin D, 1,25(OH)₂D, is formed by 1βhydroxylation of 25(OH)D, the most abundant circulating form of the vitamin. This well-characterized biochemical conversion is the rate-limiting reaction in the synthesis of 1,25(OH)₂D 1]. The classical homeostatic role of 1,25(OH)₂D is predominantly that of a calcemie agent, an action largely resulting from the metabolite's stimulation of intestinal transport of calcium 2]. Intestinal phosphorus transport, to a lesser extent than calcium transport can be stimulated by 1,25(OH)₂D 3]. Furthermore, skeletal 4] and perhaps renal activity 5] of 1,25(OH)₂D can increase circulating concentrations of calcium. These in vivo effects of 1,25(OH)₂D on mineral homeostasis raise the question of whether feedback control, via mineral regulation of 1,25(OH)₂D production, exists, and the significant mechanisms involved. Here, I will briefly review evidence from earlier studies supporting the notion of calcium and phosphorus regulation of 1α-hydroxylase activity, and present data generated in collaboration with Dr Anast examining vitamin D metabolism in magnesium deficiency.