AJP - Endocrinology and Metabolism, Vol 254, Issue 2 E150-E154, Copyright © 1988 by American Physiological Society
Metabolism of 25-hydroxyvitamin D in copper-laden rat: a model of Wilson's disease
T. O. Carpenter, M. L. Pendrak and C. S. Anast
Department of Medicine (Endocrinology), Children's Hospital, Boston, Massachusetts.
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.
