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  • Title: Renal and hepatic 1 alpha-hydroxylation of 25-hydroxyvitamin D3 in piglets suffering from pseudo vitamin D-deficiency rickets, type I.
    Author: Axén E, Harmeyer J, Wikvall K.
    Journal: Biochim Biophys Acta; 1998 Sep 30; 1407(3):234-42. PubMed ID: 9748599.
    Abstract:
    The piglets examined suffer from rickets and have symptoms similar to those of classic pseudo vitamin D-deficiency rickets, type I (PVDRI), including plasma concentrations of 1 alpha, 25-dihydroxyvitamin D3 considerably lower than in healthy control piglets. It has been suggested that the rachitic piglets have a defective renal 1 alpha,25-dihydroxyvitamin D3 production. The present study shows that partially purified mitochondrial and microsomal cytochrome P450 from kidney and liver of both rachitic and control animals is able to catalyze 1 alpha-hydroxylation of 25-hydroxyvitamin D3. The renal mitochondrial 1 alpha-hydroxylase activity was higher in the rachitic piglets whereas the renal microsomal 1 alpha-hydroxylase activity was decreased. The immunodetectable levels in kidney of a mitochondrial 1 alpha-hydroxylase (CYP27) and a microsomal 1 alpha-hydroxylase (vitamin D3 25-hydroxylase) were correlated with the 1 alpha-hydroxylase activities. The results suggest that the renal microsomal 1 alpha-hydroxylase is affected by the rachitic condition. It is concluded that the primary genetic defect of systemic 1 alpha,25-dihydroxyvitamin D3 deficiency in the rachitic PVDRI piglets does not reside in a defective function or absence of renal mitochondrial 25-hydroxyvitamin D3 1 alpha-hydroxylase. From this, it may also be concluded that PVDRI in man and pig appear to be two different forms of the disease.
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