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The page below is a sample from the LabCE course Vitamin D. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Metabolism

Cholesterol from the diet undergoes conversion to 7 dehydrocholesterol. As it circulates through the bloodstream and is taken up by cells such as skin cells, it is converted to cholecalciferol by UV exposure. Once it is converted and it enters the bloodstream, it is converted to 25-hydroxyvitamin D by the liver. It then goes to the kidneys and is finally converted to 1,25 dihydroxyvitamin D (active form).
The specific steps involved in converting vitamin D from the diet and cutaneous synthesis are illustrated in the figure below. Vitamin D, either the D2 or D3 form, is considered biologically inactive until it undergoes two enzymatic hydroxylation reactions.
The first reaction takes place in the liver by the enzyme 25-hydroxylase which forms 25(OH)D3. The second reaction takes place in the kidney, mediated by 1α-hydroxylase, which converts 25(OH)D3 to the biologically active hormone, calcitriol. 25(OH)D3, the precursor of calcitriol, is the major circulating form of vitamin D; it circulates bound to a carrier protein (vitamin D binding protein (DBP)).
The renal synthesis of calcitriol is tightly regulated by two counter-acting hormones, with up-regulation via parathyroid hormone (PTH) and down-regulation via fibroblast-like growth factor-23 (FGF23). Low serum phosphorus levels stimulate calcitriol synthesis, whereas high serum phosphorus levels inhibit it (a negative feedback system). Following its synthesis in the kidney, calcitriol binds to vitamin D binding protein (DBP) to be transported to target organs. Although the conversion to the active form occurs in the kidneys it can also occur in the skin, prostate, brain, pancreas, adipose tissue, skeletal muscle, heart, colon, monocyte/macrophages and in neoplastic tissues.