Fat-Soluble Vitamins and Vitamin C in Milk and Milk Products - Advanced Dairy Chemistry - page 535

Vitamin D 3 (obtained from dermal synthesis or from dietary sources),
which is biologically inactive, is transported to the liver where it is hydro-
xylated at the C-25 position to yield 25-hydroxyvitamin D 3 [25(OH)D 3 or
calcidiol], the major circulating form of vitamin D and the most commonly
used index of vitamin D status (van der Wielen et al., 1995). The enzyme, 25-
hydroxylase, regulates the 25-hydroxylation of vitamin D 3 to produce
25(OH)D 3 . This enzymatic conversion is dependent on the concentration of
vitamin D 3 in serum/plasma. From the liver, 25(OH)D 3 is returned to the
circulation, bound to vitamin D-binding protein (DBP) and transported to
the kidneys where the enzyme 1- -hydroxylase converts it to 1,25-dihydroxy-
cholecalciferol (1,25(OH) 2 D 3 or calcitriol), which is the major active meta-
bolite of vitamin D. 1,25(OH) 2 D 3 is estimated to be 500-1000 times more
active than 25(OH)D 3 (Henry and Norman, 1984; Reichel et al., 1989). It has
been estimated that the biological half-lives of 25(OH)D 3 and 1,25(OH) 2 D 3
are 10-20 days (Vicchio et al., 1993) and 4-6 h (Haddad and Rojanasathit,
1976; Clements et al., 1992), respectively, which partly explains why
25(OH)D 3 is a better indicator of vitamin D status than 1,25(OH) 2 D 3 .
Furthermore, the plasma level of 1,25(OH) 2 D 3 is under homeostatic control,
which further limits its value as a status marker (Holick, 1995). When
1,25(OH) 2 D 3 is in excess, the enzyme 24-hydroxylase in the kidney converts
25(OH)D 3 to 24,25-dihydroxycholecalciferol, which is biologically inactive.
Furthermore, 25(OH)D 3 can be converted to other inactive metabolites such
as 23,25-dihydroxycholecalciferol, 25,26-dihydroxycholecalciferol and
1,24,25-trihydroxycholecalciferol and excreted mainly in faeces, but the bio-
logical roles of these metabolites are not well understood (for reviews, see
Horst and Reinhardt, 1997, and Holick, 2003).

12.3.4. Role of Vitamin D in Bone Metabolism

The major biological role of 1,25(OH) 2 D 3 is to promote intestinal
calcium absorption. In addition, 1,25(OH) 2 D 3 increases the absorption of
other essential minerals across the intestine, such as phosphorus, zinc and
manganese (Biehl et al., 1995), and enhances the net renal reabsorption of
calcium and phosphorus (Singh and Dash, 1997). Thus, 1,25(OH) 2 D 3 is a
major regulator of calcium homeostasis. The classical target organs for 1,25
(OH) 2 D 3 are the intestine, bone, the kidneys and the parathyroid glands.
Normal physiological concentrations of calcium are required for proper
neuromuscular and cellular functions. Low serum calcium (hypocalcaemia)
stimulates the secretion of parathyroid hormone (PTH) from the parathyroid
gland, which, in turn, enhances the conversion of 25(OH)D 3 to 1,25(OH) 2 D 3 .
1,25(OH) 2 D 3 acts on the intestine, kidneys and bone to restore normal serum
calcium concentrations. In addition to PTH, it is also well recognized that