Figure 1.

Metabolism of vitamin D. Vitamin D (ergocalciferol and/or cholecalciferol) is produced and excreted by basal skin keratinocytes exposed to ultraviolet radiation (UV-B), or directly provided by food. While skin vitamin D is transported into the liver bound to binding proteins (DBP), dietary vitamin D is absorbed by the gastro-intestinal tract and transported to the liver via the venous circulation and chylomicron remnants. Part of the vitamin D produced is stored in fat cells and may serve as an endogenous source of vitamin D. In the liver, vitamin D2 and vitamin D3 are hydroxylated in position 25 by several enzymes found in microsomal or mitochondrial fractions. Once produced in the liver, 25(OH)D is released into the bloodstream whilst bound to DBP. Alternatively, vitamin D can be metabolized in 25(OH)D in other tissues. In the kidney, 25(OH)D is converted to the active metabolite, 1,25(OH)₂D, through the action of the enzyme 1-alpha-hydroxylase (CYP27B1), located in the proximal tubules. In excess, 1,25(OH)₂D and 25(OH)D activate 24-hydroxylase (CYP24A1) and are degraded into 24-hydroxylated products, i.e., 24,25(OH)₂D and 1,24,25(OH)₃D, which have no biological activity. Once produced in the kidney, 1,25(OH)₂D is released and transported into the bloodstream and is mainly bound to DBP until it reaches target tissues expressing the vitamin D receptor.