Calcitroic acid

Unlike the other fat-soluble vitamins, there is litde or no storage of vitamin D in the liver, except in oily fish. In human liver, concentrations of vitamin D do not exceed about 25 nmol per kg. Significant amounts may be present in adipose tissue, but this is not really storage of the vitamin, because it is released into the circulation as adipose tissue is catabolized, rather than in response to demand for the vitamin. The main storage of the vitamin seems to be as plasma calcidiol, which has a half-life of the order of 3 weeks (Holick, 1990). In temperate climates, there is a considerable seasonal variation, with plasma concentrations at the end of winter as low as half those seen at the end of summer (see Table 3.2). The major route of vitamin D excretion is in the bile, with less than 5% as a variety of water-soluble conjugates in urine. Calcitroic acid (see Figure 3.3) is the major product of calcitriol metabolism but, in addition, there are a number of other hydroxylated and oxidized metabolites. 

Most vitamin D is excreted in the bile less than 5% is excreted as water-soluble metabolites in urine. Some 2% to 3% of the vitamin D in bUe is cholecalciferol, calcidiol, and calcitriol, but most is a variety of polar metabolites and their glucuronide conjugates. In most tissues, the major pathway for inactivation of calcitriol is by way of 24-hydroxylation to calcitetrol, then onward oxidation byway of the 24-oxo-derivative, 23-hydroxylation, and oxidation to calcitroic acid (see Figure 3.3). In addition, a variety of hydroxylated and other polar metabolites have been identified in bile, and many of these onward oxidation products also undergo glucuronide conjugation in the liver (Reddy and Tserng, 1989). 

Reddy GS and Tseng KY (1989) Calcitroic acid, end product of renal metabolism of 1,25-dihydroxyvitamin D3 through C-24 oxidation pathway. Biochemistry 28,1763-9. 

Calcitroic acid 1al24l25-Trihydroxyvitamin D3 1a,25-Dihydroxyvitamin D3 25-Hydroxyvitamin D3... 

Sakaki, T, N. Sawada, Y. Nonaka, Y. Ohyama, and K. Inouye (1999). Metabolic studies using recombinant Escherichia coli cells producing rat mitochondrial CYP24. CYP24 can convert la,25-dihydroxyvitamin Dj to calcitroic acid. Eur. J. Biochem. 262, 43-48. 

Makin G, Lohnes D, Byford V, Ray R, Jones G. (1989) Target cell metabolism of 1,25-dihydroxyvi-tamin D3 to calcitroic acid. Biochem J 262 173-180... 

Hydroxylation appears to be the first step in a degradatory pathway demonstrable in vitro (55,56) (Fig. 3), which culminates in a biliary excretory form, calcitroic acid, observed in vivo (57). 

OH)D and l,25(OH)2D act as substrate for a 24-hydroxylase (an enzyme that attaches an hydroxyl on carbon-24), which is fovmd in the kidney and other target tissues for l,25(OH)2D. Once l,25(OH)2D is hydroxylated on carbon 24, this is the first step in its degradation to a water-soluble acid, calcitroic acid (Figure 4). Whereas, vitamin D is excreted in the bile, calcitroic acid is excreted by the kidney. 

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