Figure

Metabolism of vitamin D. The compound 7-dehydrocholesterol, through the effects of heat (37°C) and (UV) light (wavelength 280-305 nm), is converted into vitamin D3 in the skin. Vitamin D3 is then transported on vitamin D binding proteins (VDBP) to the liver. In the liver, vitamin D3 is converted to 25-hydroxy-vitamin D3 by the hepatic microsomal and mitochondrial cytochrome P450-containing vitamin D3 25-hydroxylase enzyme. The 25-hydroxy-vitamin D3 is transported on VDBP to the proximal tubular cells of the kidney, where it is converted to 1,25-dihydroxy-vita-min D3 by a 1-a-hydroxylase enzyme, which also is a cytochrome P450-containing enzyme. The genetic information for this enzyme is encoded on the 12q14 chromosome. Alternatively, 25-hydroxy-vitamin D3 can be converted to 24R,25-dihydroxy-vitamin D3, a relatively inactive vitamin D metabolite. 1,25-dihydroxy-vitamin D3 can then be transported by VDBP to its most important target tissues in the distal tubular cells of the kidney, intestinal epithelial cells, parathyroid cells, and bone cells. VDBP is a 58 kD a-globulin that is a member of the albumin and a-fetoprotein gene family. The DNA sequence that encodes for this protein is on chromosome 4q11-13. 1,25-dihydroxy-vitamin D3 is eventually metabolized to hydroxylated and conjugated polar metabolites in the enterohepatic circulation. Occasionally, 1,25-dihydroxy-vitamin D3 also may be produced in extrarenal sites, such as monocyte-derived cells, and may have an antiproliferative effect in certain lymphocytes and keratinocytes [1,7-9]. (Adapted from Kumar [1].)

Oral calcium Intake ~1000 mg/d

Oral calcium Intake ~1000 mg/d

Bone

200 mg

Bone

200 mg

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