Metabolism and biological activity of 25-fluorocholecalciferol, 24-dehydrocholecalciferol and 25-dehydrocholecalciferol in the rat
| Autor: | H K Schnoes, Hector F. DeLuca, Bruce L. Onisko, R S Glover |
|---|---|
| Rok vydání: | 1979 |
| Předmět: |
Male
Vitamin medicine.medical_specialty Chemical Phenomena chemistry.chemical_element Calcium Hydroxylation Nephrectomy Biochemistry Bone and Bones vitamin D deficiency chemistry.chemical_compound In vivo Internal medicine Intestine Small medicine Vitamin D and neurology Animals Molecular Biology Chromatography High Pressure Liquid Cholecalciferol Biological Transport Biological activity Cell Biology Vitamin D Deficiency medicine.disease Rats Chemistry Endocrinology chemistry lipids (amino acids peptides and proteins) Research Article |
| Zdroj: | Biochemical Journal. 182:1-9 |
| ISSN: | 0264-6021 |
| DOI: | 10.1042/bj1820001 |
| Popis: | Three side-chain analogues of cholecalciferol (vitamin D3) modified at C-25, namely 25-fluorocholecalciferol, 24-dehydrocholecalciferol and 25-dehydrocholecalciferol, conceived as potential inhibitors of the cholecalciferol 25-hydroxylase have been prepared and tested in the rat. These compounds markedly diminish conversion in vivo of cholecalciferol into 25-hydroxycholecalciferol, but are not antagonists of vitamin D action, because they themselves possess significant biological activity in vivo. Each compound is capable of stimulating the intestinal transport of calcium and the mobilization of calcium from bone in vitamin D-deficient rats. Biological responses equivalent to those generated by a physiological dose of cholecalciferol (0.05 microgram) are produced, however, only when the analogues are administered at high doses (5-50 microgram). The biological activity of 24-dehydrocholecalciferol and 25-dehydrocholecalciferol is shown to result from conversion, in vivo, to the natural hormone, 1 alpha,25-dihydroxycholecalciferol, whereas 25-fluorocholecalciferol is metabolically activated in the rat by hydroxylation to 1 alpha-hydroxy-25-fluorocholecalciferol. This latter conversion is the first reported example of the 1 alpha-hydroxylation of a vitamin D compound lacking the 25-hydroxy group. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|