Vitamin D, Calcium, Parathyroid Hormone, and Sex Steroids in Bone Health and Effects of Aging

Figure 2

Vitamin D metabolism. The production of vitamin D starts from 7-dehydrocholesterol, which is found in abundance in the skin. It can be formed from internal synthesis pathway of cholesterol formation from acetyl CoA. In the pathway, it is formed before cholesterol. It can also be obtained from diet such as milk. 7-Dehydrocholesterol is converted to previtamin D3 by breaking one of the rings using sunlight. Previtamin D3 isomerizes to form cholecalciferol (or vitamin D3), which is hydroxylated using CYP2R1 enzyme in the liver to form 25(OH)D₃ (or calcidiol). Vitamin D3 can also be obtained from diet fortified with dairy products or fatty fish. Calcidiol can be converted to 24,25(OH)₂D₃ by P450cc24 and excreted. From the liver, calcidiol is bound to vitamin D binding protein (DBP) and transported to kidneys where it is converted to 1,25(OH)₂D₃ (or calcitriol) by the enzyme CYP27B1. Calcitriol is the active form of vitamin D. Its role will be described in Figure 3. Excess calcitriol is converted to 1,24,25(OH)₃D₃ by CYP24A1 and excreted.