1. There are two forms of vitamin D.
A. Cholecalciferol (vitamin D3) – produced from the skin by the action of UV light and absorbed in the GI tract from animal food products. Most over-the-counter vitamin D preparations contain D3.
B. Ergocalciferol (vitamin D2) – plant vitamin D and also available in high doses by prescription.
2. D2and D3, once in the plasma, are converted to 25(OH)D primarily in the liver by the action of hepatic 25-hydroxylase. This step is essentially unregulated so that the amount of 25(OH)D produced is proportional to vitamin D intake, absorption, and stores. Although there are some subtle differences in the pharmacokinetics of 25(OH)D2vs. 25(OH)D3(discussed later), we will consider them equivalent right now and call the total 25(OH)D.
3. 25(OH)D is converted to 1,25(OH)2D (the active form) in the kidney via PTH-stimulated 1-hydroxylase activity. The concentration of 25(OH)D in the blood is several fold higher than 1,25(OH)2D, so only a small percentage of 25(OH)D is converted to 1,25(OH)2D. When plasma calcium is high (and, therefore PTH is low), the kidney can convert some 25(OH)D to 24,25(OH)2D (an inactive form) by the action of renal 24-hydroxylase.
4. 1,25(OH)2D has several important actions that ultimately increase plasma calcium concentration.
A. By far its most important effect is to increase GI absorptionof calcium (and phosphate).
B. Other minor effects are to directly increase bone resorption (at high concentrations), renal calcium reabsorption, and inhibition of the synthesis of PTH.