These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Investigation of the mechanism for abnormal renal 25-hydroxyvitamin D3-1-hydroxylase activity in the X-linked Hyp mouse.
    Author: Tenenhouse HS.
    Journal: Endocrinology; 1984 Aug; 115(2):634-9. PubMed ID: 6086274.
    Abstract:
    Renal mitochondria from mutant hypophosphatemic male mice (Hyp/Y) fed a vitamin D-deficient, low calcium diet synthesize significantly less 1,25-dihydroxyvitamin D3 than mitochondria from normal male (+/Y) littermates on the same diet. Kinetic studies reveal that maximum velocity (Vmax) for 25-hydroxyvitamin D3-1-hydroxylase (1-hydroxylase) is lower in Hyp/Y relative to +/Y mice (0.21 +/- 0.02 vs. 1.06 +/- 0.12 pmol/mg protein X min) whereas the apparent Michaelis-Menten constant (Km) for the reaction is not different in both genotypes (0.55 +/- 0.05 vs. 0.50 +/- 0.08 microM). The presence of an inhibitor for 1-hydroxylase activity in renal mitochondria of Hyp/Y mice was ruled out by estimating enzyme activity in mixtures of renal mitochondria from +/Y and Hyp/Y mice. Phosphate in the incubation medium stimulated 1-hydroxylase activity in +/Y mitochondria. In Hyp/Y mice, the stimulation achieved was smaller in magnitude and the added phosphate did not restore mutant 1-hydroxylase activity to normal. The vitamin D-deficient, low calcium diet led to a significant and comparable increase in serum PTH and urinary excretion of cAMP in +/Y and Hyp/Y, suggesting that the mutant strain had an appropriate PTH response to the diet-induced fall in serum calcium. Furthermore, the fractional excretion index of phosphate which is significantly greater in Hyp/Y than +/Y mice fed the control diet increased 3-fold in both genotypes fed the vitamin D-deficient, low calcium diet. These results suggest that the abnormal renal 1-hydroxylase response in Hyp mice is not the result of generalized renal resistance to PTH in the mutant strain and suggest that the defect in Hyp/Y mice may reside at a regulatory step subsequent to cAMP production.
    [Abstract] [Full Text] [Related] [New Search]