24.25- Dihydroxyvitamin D

The answers are 402-g, 403-a. (Hardman, pp 1529-1532, 1582-15853 Calcitriol (1,2.5-dihydroxyvitamin D) is the most active form of vitamin D. It is formed by the kidney. When the Ca blood level rises, the kidney produces 24,25-dihydroxyvitamin D, a much less active form. Vitamin D can be manufactured in the body by the action of sunlight on the skin. Its main action is to increase Ca absorption in the gut Thus, vitamin D subserves important hormonal functions in Ca homeostasis. 

Vitamin D is a prohormone that serves as precursor to a number of biologically active metabolites (Figure 42-3). Vitamin D is first hydroxylated in the liver to form 25-hydroxyvitamin D (25[OH]D). This metabolite is further converted in the kidney to a number of other forms, the best studied of which are 1,25-dihydroxyvitamin D (l,25[OH]2D) and 24,25-dihydroxyvitamin D (24,25[OH]2D). Of the natural metabolites, only vitamin D and l,25(OH)2D (as calcitriol) are available for clinical use (Table 42-1). Moreover, a number of analogs of l,25(OH)2D are being synthesized to extend the... 

Vitamin D that is taken up by the fiver is converted to 25-hydroxyvitamin D by a microsomal hydroxylase (Fig. 30-3). 25-Hydroxyvitamin D is the main circulating form of vitamin D in the serum and the best indicator of vitamin D status. Normal serum levels are 14-60 ng/mL (35-150 nmol/L). When serum calcium concentrations decline, 25-hydroxyvitamin D is converted to 1,25-dihydroxyvitmin D by la-hydroxylase, a mixed-function oxidase that is located in the inner mitochondrial membrane in kidney tissue and whose expression is regulated by parathyroid hormone (PTH). The main function of 1,25-dihydroxyvitamin D is to increase the intestinal absorption of dietary calcium and phosphorus. When serum concentrations of calcium and phosphorus are normal or when large doses of vitamin D are administered, 25-hydroxyvitamin D is metabolized to 24,25-dihydroxyvitamin D in the renal... 

The skin has a well-documented role in vitamin D metabolism. 7-Dehydrocho-lesterol (provitamin D3) is activated by exposure to ultraviolet radiation in the skin to previtamin D3, which isomerizes to vitamin D3. Recently, further metabolism of 24,25-dihydroxyvitamin D to biologically active 1,25-dihydroxy vitamin D has also been demonstrated in skin, a conversion previously assumed to occur only in the kidney. 

In a further study, serum concentrations of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and la,25-dihydroxyvitamin D were measured in 10 Cd-exposed subjects and 5 non-exposed subjects [100]. The Cd-exposed subjects were divided into two groups according to serum la,25-dihydroxyvitamin D levels. No significant differences for 25-hydroxyvitamin D were found between the Cd-exposed group with low or normal serum la,25-dihydroxyvitamin D and the... 

H)D-la-hydroxylase, whereas hypocalcemia acts indirectly by stimulating the secretion of PTH. Hypercalcemia, hyperphosphatemia, and 1,25(0H)2D reduce 25 (OH) D-la-hydroxylase and 1,25(0H)2D. 1,25(0H)2D also induces 25(OH)D-24-hydroxylase, an enzyme producing 24,25-dihydroxyvitamin D (24,25 [OH]2D), the most prevalent... 

Markestad T. Plasma concentrations of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25,26-dihydroxyvitamin D in the first year of life. 

Larsson, D., Nemere, L, Sundell, K. 2001. Putative basal lateral membrane receptors for 24,25-dihydroxyvitamin D(3) in carp and Atlantic cod enterocytes Characterization of binding and effects on intracellular calcium regulation. J. Cell Biochem. 83(2) 171-86. 

The second stage of vitamin D metabolism occurs in the kidney, where calcidiol undergoes either 1-hydroxylation to yield the active metabolite 1,2 5-dihydroxyvitamin D (calcitriol) or 24-hydroxylation to yield an apparently inactive metabolite, 24,25-dihydroxyvitamin D (24-hydroxycalcidiol). 

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