Fig. 2

Uptake, synthesis, and metabolism of vitamin D2 and D3. Vitamin D can be obtained through natural sun exposure and from dietary sources such as fish, mushrooms, cheeses, milk, butter, cereal, and whole grains. Vitamin D3 is synthesized in the skin when pro-vitamin D3 (7-dehydrocholesterol) is converted to pre-vitamin D3 in response to sunlight exposure (ultraviolet B radiation). Alternatively, Vitamin D3 can be obtained from natural or fortified foods and supplements from vitamin D2 (ergocalciferol) and vitamin D3. After entering the bloodstream, vitamin D2 and D3 bind to vitamin D-binding protein (DBP) and are transported to the liver where they are hydroxylated by liver 25-hydroxylases to form 25-hydroxycholecalciferol [25(OH)D] (calcifediol or calcidiol). 25(OH)D is then transported to the kidney where it is further hydroxylated by 1α-hydroxylase to produce the active secosteroid 1,25(OH)2D (calcitriol). The synthesis of 1,25(OH)2D is regulated by parathyroid hormone and is suppressed by calcium, phosphate, and 1,25(OH)2D itself