Abnormal 24-hydroxylation of 25-hydroxyvitamin D in the X-linked hypophosphatemic mouse.
The effect of extracellular phosphate on the control of 25-hydroxyvitamin D3 24-hydroxylase was studied in normal mice and littermates with X-linked hypophosphatemic rickets (Hyp). 24-Hydroxylase activity and plasma concentrations of 24,25-dihydroxyvitamin D3 were significantly higher in Hyp mice than in normal mice when both groups were fed a normal diet containing 1.22% calcium (Ca) and 0.8% phosphorus (Pi). The differential in 24-hydroxylase activity was exaggerated when serum phosphate was reduced in normal mice by means of a low Pi diet or increased in Hyp mice by means of a high Pi diet. Differences in 24-hydroxylase activity between the two groups of mice were also demonstrated in the presence of varying Pi concentrations in vitro. Thus, in both Hyp and normal mice, 24-hydroxylase activity is influenced in a qualitatively similar manner by serum Pi. Plasma concentrations of 1,25-dihydroxyvitamin D3 were the same in normal and Hyp mice. The data are consistent with the hypothesis that control the renal metabolism of 25-hydroxyvitamin D3 in Hyp mice is reset such tht 24-hydroxylase activity is inappropriate high for the prevailing serum phosphate over a wide range of concentrations.
D015650:24,25-Dihydroxyvitamin D 3; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D000818:Animals; D002112:Calcifediol / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D003577:Cytochrome P-450 Enzyme System; D004032:Diet; D004100:Dihydroxycholecalciferols / Q000097:blood; D007015:Hypophosphatemia, Familial / Q000097:blood / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010710:Phosphates / Q000097:blood; D013250:Steroid Hydroxylases / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D004100:Dihydroxycholecalciferols; D010710:Phosphates; D015650:24,25-Dihydroxyvitamin D 3; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002112:Calcifediol; D002118:Calcium