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 transformed and enters the bloodstream, the liver converts it to 25-hydroxyvitamin D. It goes to the kidneys and is finally converted to 1,25 dihydroxy vitamin D (active form).
The figure below illustrates the specific steps in converting vitamin D from the diet and cutaneous synthesis. Vitamin D, either the D2 or D3 form, is considered biologically inactive until it undergoes two enzymatic hydroxylation reactions.
The first reaction occurs in the liver through the enzyme 25-hydroxylase, which forms 25(OH)D3. The second reaction occurs 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 primary 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). After synthesizing 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 neoplastic tissues.
