In vitro regulation of kidney 25-hydroxyvitamin D3-hydroxylase enzyme activities by vitamin D3 metabolites. Molecular specificity and mechanism of action

J. L. Omdahl, L. A. Hunsaker, Andrew Evan, P. Torrez

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

An acute chick kidney tubule model was used to evaluate the molecular specificity of steroids which act to inhibit kidney 25-hydroxyvitamin D3-1-hydroxylase and induce 25-hydroxyvitamin D3-24-hydroxylase enzyme activities. Such hydroxylase-regulatory activity was confirmed to the vitamin D family of secosteroids. Vitamin D3 per se was not active. Rather, expression of hydroxylase-regulatory activity required acquisition of a C-25 hydroxyl grouping. Of the metabolites tested, 25-hydroxyvitamin D3 demonstrated the greatest hydroxylase-regulatory activity. Metabolites of 25-hydroxyvitamin D3 which contained hydroxyl groups at carbon atoms 1, or 24, or both, were also active in regulating the kidney hydroxylase enzymes. The hydroxylase-regulatory action of 1,25-dihydroxyvitamin D3 was blocked by inhibitors of RNA or protein synthesis, implicating a requirement for de novo protein synthesis. It was suggested that the regulatory process involves both hydroxylase-enzyme synthesis and turnover as well as enzyme-level modulation of endogenous enzyme activities.

Original languageEnglish (US)
Pages (from-to)7460-7466
Number of pages7
JournalJournal of Biological Chemistry
Volume255
Issue number15
StatePublished - 1980
Externally publishedYes

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Calcifediol
Cholecalciferol
Enzyme activity
Metabolites
Mixed Function Oxygenases
Kidney
Enzymes
Hydroxyl Radical
Secosteroids
Kidney Tubules
Nucleic Acid Synthesis Inhibitors
Protein Synthesis Inhibitors
In Vitro Techniques
Calcitriol
Vitamin D
Carbon
Steroids
Modulation
Atoms

ASJC Scopus subject areas

  • Biochemistry

Cite this

In vitro regulation of kidney 25-hydroxyvitamin D3-hydroxylase enzyme activities by vitamin D3 metabolites. Molecular specificity and mechanism of action. / Omdahl, J. L.; Hunsaker, L. A.; Evan, Andrew; Torrez, P.

In: Journal of Biological Chemistry, Vol. 255, No. 15, 1980, p. 7460-7466.

Research output: Contribution to journalArticle

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