Evidence for extrarenal metabolism of 25-hydroxyvitamin D3 in man

1986 ◽  
Vol 71 (1) ◽  
pp. 89-95 ◽  
Author(s):  
L. J. Fraher ◽  
S. Adami ◽  
S. E. Papapoulos ◽  
H. L. Sudan ◽  
R. J. McGonigle ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
Chronic Haemodialysis ◽  
Dependent Manner ◽  
Dihydroxyvitamin D3 ◽  
Daily Ingestion ◽  
Normal Relationship ◽  
24,25 Dihydroxyvitamin D3

1. Metabolites of vitamin D3 were measured in the circulation of four patients on chronic haemodialysis (three of whom were surgically anephric) before and during daily ingestion of 40000 i.u. of cholecalciferol. 2. Circulating 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] was measurable, but abnormally low before treatment; its circulating concentration rose in a substrate dependent manner when serum 25-hydroxyvitamin D3 (25-OHD3) increased, but the response was reduced when compared with the normal relationship. 3. Serum 1,25-hydroxyvitamin D3 [1,25-(OH)2D3] and calcidiol lactone (25-OHD3-lactone) were consistently unmeasurable in sera from these patients before administration of cholecalciferol. However, when serum 25-OHD3 rose with treatment, 1,25-(OH)2D3 became detectable in the sera of three of the four patients and 25-OHD3-lactone could be measured in all of them. 4. These data indicate that extrarenal sites of synthesis of 24,25-(OH)2D3, 25-OHD3-lactone and 1,25-(OH)2D3 exist in chronically dialysed patients but require large amounts of substrate to be significant.

scholarly journals Metabolism and pharmacokinetics of 24,25-dihydroxyvitamin D3 in the vitamin D3-replete rat.

1985 ◽  
Vol 260 (25) ◽  
pp. 13625-13630
Author(s):  
K Jarnagin ◽  
S Y Zeng ◽  
M Phelps ◽  
H F DeLuca
Keyword(s):  
Vitamin D3 ◽  
Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

The Effect of Vitamin D and Its Metabolites on Fracture Repair in Chicks

1983 ◽  
Vol 65 (4) ◽  
pp. 429-436 ◽  
Author(s):  
S. Dekel ◽  
R. Salama ◽  
S. Edelstein
Keyword(s):  
Vitamin D ◽  
Bone Formation ◽  
Vitamin D3 ◽  
Fracture Repair ◽  
Control Group ◽  
Clinical Implications ◽  
Torsional Stress ◽  
Active Vitamin ◽  
Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

1. One-day-old chicks were depleted of vitamin D. At 3 weeks their right tibiae, and those of a control group given vitamin D3, were fractured and pinned. After fracture the controls were kept on vitamin D3. Another group was left vitamin D-deficient. The remaining depleted chicks, divided into four groups, were given vitamin D3, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or a combination of 24,25(OH)2D3 and 1,25(OH)2D3. 2. The callus obtained after 9 and 14 days was subjected to torsional stress. The callus of chicks given vitamin D continuously showed the greatest resistance, whereas that of vitamin D-deficient chicks showed the smallest resistance. Repletion with either vitamin D3 or its metabolites increased the strength of the callus. Repletion with the combination of 24,25(OH)2D3 and 1,25(OH)2D3 produced the most marked results, in that the callus was even stronger than that of chicks replete with vitamin D3. 3. It is concluded that 24,25(OH)2D3 is essential for bone formation in addition to the known active vitamin D metabolite 1,25(OH)2D3, and the possible clinical implications of these findings are discussed.

Effects of vitamin D and diet magnesium on magnesium metabolism

1980 ◽  
Vol 239 (6) ◽  
pp. E515-E523 ◽  
Author(s):  
B. S. Levine ◽  
N. Brautbar ◽  
M. W. Walling ◽  
D. B. Lee ◽  
J. W. Coburn
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Tubular Reabsorption ◽  
Transport Processes ◽  
Separate Experiment ◽  
Dihydroxyvitamin D3 ◽  
Magnesium Metabolism ◽  
1,25 Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

Effects of 6-9 days of vitamin D3 (D3), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], or 1,24,25-trihydroxyvitamin D3 [1,24,25(OH)3D3] on Mg metabolism were studied in vitamin D-deficient (-D) rats. Mg absorption expressed as percent intake increased with 1,25(OH)2D3 and 1,24,25(OH)3D3. Urinary Mg (UMg) increased with no change in serum Mg (SMg) or Mg balance. 1,25(OH)2D3 was threefold more potent than 1,24,25(OH)3D3 in raising serum Ca and Mg absorption. In a separate experiment in pair-fed rats given D3, 1,25-(OH)2D3, or 1,24,25(OH)3D3, the diet contained either 0.03 or 0.2% Mg; 1,25(OH)2D3 and D3 lowered SMg after 3 days; UMg increased after 24 h to remain elevated. D3 and 1,25(OH)2D3 augmented Mg absorption; feeding 0.2% Mg lowered Mg absorption in -D animals. All sterols augmented Mg absorption in -D rats; both the earlier action of 1,25(OH)2D3 and 1,24,25(OH)3D3 suggests that 1-hydroxylation is necessary. Suppressed Mg absorption with 0.2% Mg in -D rats suggests two transport processes, with one vitamin D dependent. Higher UMg with decreased SMg with 1,25(OH)2D3 suggests reduced tubular reabsorption.

The ratio of serum 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 is predictive of 25-hydroxyvitamin D3 response to vitamin D3 supplementation

2011 ◽  
Vol 126 (3-5) ◽  
pp. 72-77 ◽  
Author(s):  
Dennis Wagner ◽  
Heather E. Hanwell ◽  
Kareena Schnabl ◽  
Mehrdad Yazdanpanah ◽  
Samantha Kimball ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
Dihydroxyvitamin D3 ◽  
Vitamin D3 Supplementation ◽  
24,25 Dihydroxyvitamin D3

Effect of vitamin D3, 25-hydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 on parathyroid hormone secretion

1987 ◽  
Vol 41 (1) ◽  
pp. 48-51 ◽  
Author(s):  
Larry K. Cantley ◽  
John B. Russell ◽  
Deborah S. Lettieri ◽  
Louis M. Sherwood
Keyword(s):  
Parathyroid Hormone ◽  
Vitamin D3 ◽  
Hormone Secretion ◽  
Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

Effect of vitamin D3 metabolites on calcium and phosphorus metabolism in chick embryos

1985 ◽  
Vol 248 (3) ◽  
pp. E281-E285 ◽  
Author(s):  
L. E. Hart ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Embryonic Development ◽  
Vitamin D3 ◽  
Chorioallantoic Membrane ◽  
Sole Source ◽  
Chick Embryos ◽  
Dihydroxyvitamin D3 ◽  
Total Body Calcium ◽  
1,25 Dihydroxyvitamin D3 ◽  
24,25 Dihydroxyvitamin D3

The biochemical nature of the physiological defect found in chick embryos from hens supported on 1,25-dihydroxyvitamin D3 as their sole source of vitamin D is described. Vitamin D-deficient hens (44-wk-old) were divided into six groups of five and dosed daily for 19 wk with either 2.0 micrograms of 25-hydroxyvitamin D3, 2.0 micrograms of 24,24-difluoro-25-hydroxy-vitamin D3, 0.4 micrograms of 1,25-dihydroxyvitamin D3, 2.0 micrograms of 24,25-dihydroxyvitamin D3, 0.4 micrograms of 1,25-dihydroxyvitamin D3 plus 2.0 micrograms of 24,25-dihydroxyvitamin D3, or vehicle only. Normal embryonic development was found in eggs from hens given 25-hydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3, whereas embryos from hens given 1,25-dihydroxyvitamin D3, 24,25-dihydroxyvitamin D3, or their combination were abnormal and failed to hatch. Embryos from hens fed 1,25-dihydroxyvitamin D3 and/or 24,25-dihydroxyvitamin D3 had vitamin D deficiency: low bone ash, low plasma calcium, low total body calcium, and extremely high plasma phosphorus. Because the shell is the major source of calcium for the developing embryo, calcium transport from the shell to the embryos across the chorioallantoic membrane apparently fails, giving rise to the observed defects in embryonic development.

An in vitro Experimental Insight into the Osteoblast Responses to Vitamin D3 and Its Metabolites

Pharmacology ◽  
2018 ◽  
Vol 101 (5-6) ◽  
pp. 225-235 ◽  
Author(s):  
Dong Wang ◽  
Jiang Song ◽  
Huasong Ma
Keyword(s):  
Vitamin D3 ◽  
Osteoblast Differentiation ◽  
Cell Types ◽  
Cell Counting ◽  
Dependent Manner ◽  
Dihydroxyvitamin D3 ◽  
Osteogenic Markers ◽  
Polymerase Chain ◽  
Dose Dependent

Background: 25-hydroxyvitamin D3 (25[OH]VD3) has recently been found to be an active hormone. Its biological actions are also demonstrated in various cell types. However, the precise influences of vitamin D3 (VD3) and its metabolites (25[OH]VD3, 1α,25-dihydroxyvitamin D3 [1α,25-(OH)2VD3]) on the osteoblast differentiation remain largely unknown. In this work, we investigated the effects of VD3 and its metabolites in different concentrations on the early and later osteoblast differentiation and biomineralization. Methods: We first used quantitative real-time polymerase chain reaction (RT-qPCR) to evaluate the responsiveness of osteoblasts to VD3, 25(OH)VD3 or 1α,25-(OH)2VD3. We also evaluated the proliferation, differentiation and biomineralization of osteoblast at different time points via cell counting kit-8 assay and the analysis of osteogenic markers. Results: The experimental results confirmed that osteoblasts could be responsive to 25(OH)VD3 and 1α,25-(OH)2VD3 but could not directly metabolize VD3 and 25(OH)VD3. Only 200 nmol/L VD3 significantly promoted osteoblast proliferation, while 25(OH)VD3 and 1α,25-(OH)2VD3 did not show obvious actions. Moreover, the early osteogenic markers were increased by 25(OH)VD3 and 1α,25-(OH)2VD3 in a dose-dependent manner. More importantly, only 25(OH)VD3 had accelerated the gene and protein expressions of osteocalcin and the biomineralization level of osteoblasts. Conclusions: Our findings provide reliable evidence that 25(OH)VD3 at 100–200 nmol/L can induce the early and later osteoblast differentiation and biomineralization for clinical bone tissue engineering.

scholarly journals Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D3 Analogues and Their Stability to hCYP24A1-Dependent Catabolism

2021 ◽  
Vol 22 (21) ◽  
pp. 11863
Author(s):  
Fumihiro Kawagoe ◽  
Sayuri Mototani ◽  
Kaori Yasuda ◽  
Hiroki Mano ◽  
Toshiyuki Sakaki ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
Stereoselective Synthesis ◽  
Side Chain ◽  
Synthetic Route ◽  
Main Metabolite ◽  
Dihydroxyvitamin D3 ◽  
Synthetic Intermediates ◽  
24,25 Dihydroxyvitamin D3

Two 24-fluoro-25-hydroxyvitamin D3 analogues (3,4) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D3 side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24R)- and (24S)-24-fluoro-25-hydroxyvitamin D3 revealed that the C24-R-configuration isomer 4 was more resistant to CYP24A1-dependent metabolism than its 24S-isomer 3. The new synthetic route of the CYP24A1 main metabolite (24R)-24,25-dihydroxyvitamin D3 (6) and its 24S-isomer (5) was also studied using synthetic intermediates (30,31) in parallel.

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