title: Metabolism of 25-hydroxyvitamin D in copper-laden rat: a model of Wilson's disease.
abstract: Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. We investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D3 [25(OH)D3] resulted in reduced 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in copper-intoxicated rats. In vitro 25(OH)D-1 alpha-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondria from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH)2D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease.
authors.affiliation: Department of Medicine (Endocrinology), Children's Hospital, Boston, Massachusetts.
authors.forename: T O
authors.initials: TO
authors.lastname: Carpenter
authors.forename: M L
authors.initials: ML
authors.lastname: Pendrak
authors.forename: C S
authors.initials: CS
authors.lastname: Anast
mesh_terms: D000818:Animals; D053493:Cholestanetriol 26-Monooxygenase; D003300:Copper / Q000493:pharmacokinetics*; D006527:Hepatolenticular Degeneration / Q000378:metabolism*; D006887:Hydroxycholecalciferols / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D006887:Hydroxycholecalciferols; D003300:Copper; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase