Synthesis of calcitriol Synthesis of calcitriol. The dermal layer of the skin is capable of synthesizing 7-dehydrocholesterol (7-DH cholesterol); on ultraviolet (UV) light exposure, this compound is converted to cholecalciferol, or vitamin D3. Cholecalciferol is avidly bound by vitamin D–binding protein (DBP) and transported in the circulation to the liver, where the DBP is released and the vitamin D3 is rapidly taken up by the hepatocyte. Cholecalciferol is converted to biologically inactive 25-OH cholecalciferol or 25(OH)D3 by the action of a 25-hydroxylase that is a member of the cytochrome P450 family. On exit from the hepatocyte, 25-(OH)D3 is bound tightly to DBP and transported to the kidney, where it is filtered at the glomerulus and taken up at the brush-border surface of the proximal tubule by endocytosis after binding to megalin. The DBP is degraded within the tubule cell, and the megalin–25(OH)D3 complex is transported to the mitochondrion, where the megalin is released for degradation; within the mitochondrion, the free 25-OH cholecalciferol is acted on by a second P450 enzyme, 1α-hydroxylase, to form 1,25(OH)2 D3, or calcitriol. On release from the tubule cell across the antiluminal surface, the calcitriol is again bound to DBP, and the bulk circulates as the complex; only a very small fraction remains free in the circulation. PTH, parathyroid hormone. Source: Disorders of Calcium, Phosphate, and Bone Metabolism, Pediatric Endocrinology and Inborn Errors of Metabolism, 2e Citation: Sarafoglou K, Hoffmann GF, Roth KS. Pediatric Endocrinology and Inborn Errors of Metabolism, 2e; 2017 Available at: http://accesspediatrics.mhmedical.com/DownloadImage.aspx?image=/data/books/2042/saraped2_ch40_f003.png&sec=154116072&BookID=2042&ChapterSecID=154116042&imagename= Accessed: November 09, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved