Unique Biosynthesis by Kidney of a Biologically Active Vitamin D Metabolite

Vitamin D

“…This polar compound became of great interest when Kodicek et al (1970), Haussler et al (1971 and Myrtle & Norman (1971) showed that it was more active than D3 in producing increased intestinal absorption of calcium. A major advance occurred very shortly afterwards when Fraser & Kodicek (1970) established conclusively that the kidney was the unique site of biosynthesis of this biologically active vitamin D metabolite. This was soon confirmed (Norman et al, 1971a;Gray ef al., 1971) and shortly afterwards the chemical identity of the metabolite was established by three groups using a combination of mass spectrometry, ultraviolet absorption spectrophotometry, and specific chemical reactions, as 1,25-dihydroxycholecalciferol (Lawson et al, 1971;Norman et al, 1971b;Holick et al, 1971).…”

“…This step occurs in the liver (Blunt et al, 1968), gut (Tucker er al., 1973), kidney, and perhaps other organs. It is not clear which of these sites is the most important in man but the critical metabolic step occurs in the kidney, and only in the kidney (Fraser & Kodicek, 1970). The most active compound is formed by introduction of a new hydroxyl group at position 1 in the aconfiguration to produce la-25-dihydroxycholecalciferol (Fig.…”

Target cell metabolism of 1,25-dihydroxyvitamin D3 to calcitroic acid. Evidence for a pathway in kidney and bone involving 24-oxidation

“…After activation to its hormonal form, la,25-dihydroxyvitamin D3 [1,25(OH)2D3] (Fraser & Kodicek, 1970), the molecule is able to execute its actions in a variety of targets including the intestinal mucosal cell, the osteoblast and the renal tubular cell (Price & Baukol, 1980;Nemere et al, 1984;Chandler et al, 1984). The mechanism by which 1,25(OH)2D3 acts at target cells involves a specific steroid-hormone-like receptor protein, the gene for which has been recently isolated and cloned (McDonnell et al, 1987).…”

Peritonitis induces the synthesis of 1α,25‐dihydroxyvitamin D3 in macrophages from CAPD patients

“…The hormonally active metabolite of vitamin D3, I ol,25-dihydroxyvitamin D3 [IoG25(OH)2D3], which promotes intestinal absorption of calcium, is normally synthesized exclusively in the kidney from its precursor 25-hydroxyvitamin D3 (25OHD3) [1]. However, patients with sarcoidosis who are hypercalcaemic have elevated plasma levels of lo~,25(OH)zD3 [2] thought to result from extra-renal synthesis by activated macrophages (Me) [3].…”