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Production in vitro of 1 alpha 25 di hydroxy vitamin d 3 26 23 lactone from 1 alpha 25 di hydroxy vitamin d 3 by rat small intestinal mucosa homogenates



Production in vitro of 1 alpha 25 di hydroxy vitamin d 3 26 23 lactone from 1 alpha 25 di hydroxy vitamin d 3 by rat small intestinal mucosa homogenates



Archives of Biochemistry & Biophysics 213(1): 139-147



The metabolism of 1.alpha.,25-dihydroxyvitamin D3[1.alpha.,25(OH)2D3] in the rat was studied under in vivo and in vitro conditions. A time course study of the appearance of 1.alpha.,25-dihydroxyvitamin D3-26,23-lactone in the plasma following i.v. or oral administration of 1.alpha.,25(OH)2D3 suggests that the small intestine may take part in production of the 1.alpha.,25(OH)2D3-26,23-lactone. In an in vitro study using a homogenate of rat small intestinal mucosa, 1.alpha.,25(OH)2D3 undergoes further metabolism to give more polar metabolite(s) which comigrate with authentic 1.alpha.,24,25-trihydroxyvitamin D3 [1.alpha.,24,25(OH)3D3] on Sephadex LH-20 column chromatography. The metabolic profile obtained after high-pressure liquid chromatography reveals 2 major classes of metabolites, designated Peaks X and Y. Peak X is an unidentified metabolite of 1.alpha.,25(OH)2D3. Peak Y is chromatographically identical with 1.alpha.,25-dihydroxyvitamin D3-26,23-lactone which was recently isolated from the plasma of rats and dogs as a major metabolite produced in vivo from 1.alpha.,25(OH)2D3 or 1.alpha.-hydroxyvitamin D3. The enzyme activity which produces metabolites X and Y in the rat intestinal homogeantes is induced in vitamin D-replete rats by pretreatment of the animals with i.v. 1.25 .mu.g/kg doses of 1.alpha.,25-dihydroxyvitamin D3, 6 to 8 h previously.

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Accession: 006190576

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PMID: 6895820



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