Derived from cholesterol, vitamin D is biosynthesized from its prohormone cholecalciferol (D3), the product of
solar ultraviolet irradiation of 7-dehydrocholesterol in the skin.
In 1966, it was first recognized that vitamin
D must undergo activation via two oxidative metabolic steps. The first oxidation to
25-hydroxycholecalciferol (25(OH)D3: calcifediol; Calderol) occurs in the endoplasmic reticulum of the liver and
is catalyzed by vitamin D 25-hydroxylase. This activation step is not
regulated by plasma calcium concentrations. The major circulating form (10–80 μg/mL) is 25(OH)D3, which also
is the primary storage form of vitamin D.
Sterol-specific cytoplasmic receptor proteins (vitamin D receptor) mediate the biological action of vitamin D.
The active hormone is transported from the cytoplasm to the nucleus via the vitamin D receptor, and as a result
of the interaction of the hormone with target genes, a variety of proteins are produced that stimulate the
transport of calcium in each of the target tissues
Active vitamin D works in concert with PTH to enhance active
intestinal absorption of calcium, to stimulate bone resorption, and to prohibit renal excretion of calcium. If
serum calcium or 1,25-calcitriol concentrations are elevated, then vitamin D 24-hydroxylase (in renal
mitochondria) is activated to oxidize 25(OH)D3 to inactive 24,25-dihydroxy-cholecalciferol and to further oxidize
active vitamin D to the inactive 1,24,25-trihydroxylated derivative. Both the 1,24,25-trihydroxylated and the
24,25-dihydroxylated products have been found to suppress PT H secretion as well. The biosynthesis of vitamin D is tightly regulated based on the serum concentrations of calcium, phosphate, PTH, and active vitamin D.
