Cholecalciferol, also called as vitamin D3, is produced naturally by ultraviolet irradiation of the provitamin, 7-dehydrocholesterol (a precursor of vitamin D) in the skin. Absorbed cholecalciferol requires metabolic activation. The circulating vitamin undergoes hydroxylation in the liver with the help of the enzyme, vitamin D 25-hydroxylase to form 25-hydroxycholecalciferol (calcidiol), which is the predominant circulating metabolite. Further hydroxylation in the kidneys (in response to need for phosphorus and calcium) forms 1,25-dihydroxycholecalciferol (calcitriol) with the help of 1alpha-hydroxylase. Calcidiol possesses some intrinsic activity, but calcitriol is the most active vitamin D metabolite with respect to initiating intestinal transport of calcium and phosphate and mobilizing calcium from bone. Calcitriol may prevent phosphaturia by inhibiting parathyroid hormone secretion. Conversion to calcitriol is stimulated by the parathyroid hormone, as well as decreases in serum inorganic phosphate levels. Reduced renal conversion of calcidiol to calcitriol contributes to altered calcium haemostasis and osteodystrophy in uraemia.
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