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. 2013 Mar 3;6(2):211–215. doi: 10.1093/ckj/sft008

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© The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

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Fig. 4. — Mechanisms of vitamin D metabolism and its regulation in health (A) and CYP24A1 deficiency (B). (A) 25OHD₃ is activated to 1,25(OH)₂D₃ by the enzyme CYP27B1. Via the enzyme CYP24A1, 25OHD₃ is inactivated to 24,25(OH)₂D₃, 1,25(OH)₂D₃ to calcitroic acid. In a feed-back loop, 1,25(OH)₂D₃ inhibits CYP27B1 and enhances the activity of CYP24A1. 1,25(OH)₂D₃ inhibits PTH secretion and formation, whereas PTH itself activates CYP27B1 and inhibits CYP24A1. 1,25(OH)₂D₃ stimulates FGF23 secretion which inhibits CYP27B1 and enhances CYP24A1. PTH stimulates FGF23 production, whereas FGF23 decreases PTH secretion. (B) Due to the W210R missense mutation, CYP24A1 activity is reduced resulting in increased levels of 25OHD₃ and reduced levels of 24,25(OH)₂D₃. Increased 1,25(OH)₂D₃ (normalizing over years due to the adaptive mechanism as described below, but inadequately high given the hypercalcaemia) suppresses PTH levels and enhances FGF23 secretion. Low PTH and high FGF23 decrease CYP27B1 activity resulting in normal levels of 1,25(OH)₂D₃ over time. Hypercalcaemia and low PTH cause hypercalciuria which leads to nephrocalcinosis, further aggravated by the hyperphosphaturia caused by high FGF23 levels. PTH, parathyroid hormone; FGF23, fibroblast growth factor 23; 25OHD₃, 25-hydroxyvitamin D₃; 1,25 (OH)₂D₃, 1,25-dihydroxyvitamin D₃; 24,25(OH)₂D₃, 24,25-dihydroxyvitamin D₃. Plus indicates stimulation; minus indicates inhibition; plus sign within parenthesis indicates decreased stimulation; minus sign within parentheses indicates reduced inhibition.