Biological activity of 1,25-dihydroxyvitamin D2 and 24-epi-1,25-dihydroxyvitamin D2

1988 ◽  
Vol 254 (4) ◽  
pp. E402-E406
Author(s):  
H. F. DeLuca ◽  
R. R. Sicinski ◽  
Y. Tanaka ◽  
P. H. Stern ◽  
C. M. Smith
Keyword(s):  
Biological Activity ◽  
Calcium Transport ◽  
Inorganic Phosphorus ◽  
Short Term ◽  
Dihydroxyvitamin D3 ◽  
Intestinal Calcium Transport ◽  
Fetal Rat ◽  
Bone Calcium ◽  
Biological Effectiveness

The biological activity of 1,25-dihydroxyvitamin D2 [1,25(OH)2D2] and 24-epi-1,25-dihydroxyvitamin D2 [24-epi-1,25(OH)2D2] has been determined in vitamin D-deficient rats. The biological effectiveness of 1,25(OH)2D2 is equal to that reported previously for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (15) in intestinal calcium transport, mineralization of bone, mobilization of bone calcium, and elevation of plasma inorganic phosphorus of rachitic rats. However, 24-epi-1,25(OH)2D2 is at best one-half as active as 1,25(OH)2D2 in stimulating intestinal calcium transport and in the mineralization of rachitic bone. The 24-epi-1,25(OH)2D2 is one-third as active as 1,25(OH)2D3 in binding to the chick intestinal receptor for 1,25(OH)2D3. Thus receptor discrimination may account for the twofold difference in intestinal calcium transport activity. 24-Epi-1,25(OH)2D2 appeared inactive in in vivo mobilization of bone calcium or bone phosphorus. On the other hand, in fetal rat bone in culture, the epi compound was only five times less active than 1,25(OH)2D2 in inducing resorption. Short-term experiments on bone mineral mobilization in vivo show that the 24-epi-1,25(OH)2D2 does induce bone calcium mobilization but that its activity in this respect is short lived. It is suggested that 24-epi-1,25(OH)2D2 and, as a result, it shows preferential activity on intestine whose response to a single dose of 1,25(OH)2D2 remains for several days, whereas the short-lived bone system does not remain stimulated during the 24-h period between doses.

Biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3

1983 ◽  
Vol 244 (2) ◽  
pp. E159-E163
Author(s):  
S. Okamoto ◽  
Y. Tanaka ◽  
H. F. DeLuca ◽  
Y. Kobayashi ◽  
N. Ikekawa
Keyword(s):  
Biological Activity ◽  
Calcium Transport ◽  
Plasma Calcium ◽  
Epiphyseal Plate ◽  
Dihydroxyvitamin D3 ◽  
Responsive Systems ◽  
1,25 Dihydroxyvitamin D3 ◽  
Bone Calcium ◽  
Calcium And Phosphorus

The biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3 was compared with 1,25-dihydroxyvitamin D3 in the rat. The 24,24-difluoro-1,25-dihydroxyvitamin D3 has a potency of approximately 5-10 times that of 1,25-dihydroxyvitamin D3 in the known in vivo vitamin D responsive systems. These systems include intestinal calcium transport, bone calcium mobilization, calcification of epiphyseal plate cartilage, and elevation of plasma calcium and phosphorus concentrations. Thus, 24,24-difluoro-1,25-dihydroxyvitamin D3 is the first known analogue with higher potency than 1,25-dihydroxyvitamin D3 in vivo.

scholarly journals Epimers of Vitamin D: A Review

2020 ◽  
Vol 21 (2) ◽  
pp. 470 ◽  
Author(s):  
Bashar Al-Zohily ◽  
Asma Al-Menhali ◽  
Salah Gariballa ◽  
Afrozul Haq ◽  
Iltaf Shah
Keyword(s):  
Vitamin D ◽  
Biological Activity ◽  
Hydroxyl Group ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D3 ◽  
In Vivo Models ◽  
Vitamin D Receptors ◽  
Potential Factors

In this review, we discuss the sources, formation, metabolism, function, biological activity, and potency of C3-epimers (epimers of vitamin D). We also determine the role of epimerase in vitamin D-binding protein (DBP) and vitamin D receptors (VDR) according to different subcellular localizations. The importance of C3 epimerization and the metabolic pathway of vitamin D at the hydroxyl group have recently been recognized. Here, the hydroxyl group at the C3 position is orientated differently from the alpha to beta orientation in space. However, the details of this epimerization pathway are not yet clearly understood. Even the gene encoding for the enzyme involved in epimerization has not yet been identified. Many published research articles have illustrated the biological activity of C3 epimeric metabolites using an in vitro model, but the studies on in vivo models are substantially inadequate. The metabolic stability of 3-epi-1α,25(OH)2D3 has been demonstrated to be higher than its primary metabolites. 3-epi-1 alpha, 25 dihydroxyvitamin D3 (3-epi-1α,25(OH)2D3) is thought to have fewer calcemic effects than non-epimeric forms of vitamin D. Some researchers have observed a larger proportion of total vitamin D as C3-epimers in infants than in adults. Insufficient levels of vitamin D were found in mothers and their newborns when the epimers were not included in the measurement of vitamin D. Oral supplementation of vitamin D has also been found to potentially cause increased production of epimers in mice but not humans. Moreover, routine vitamin D blood tests for healthy adults will not be significantly affected by epimeric interference using LC–MS/MS assays. Recent genetic models also show that the genetic determinants and the potential factors of C3-epimers differ from those of non-C3-epimers.Most commercial immunoassays techniques can lead to inaccurate vitamin D results due to epimeric interference, especially in infants and pregnant women. It is also known that the LC–MS/MS technique can chromatographically separate epimeric and isobaric interference and detect vitamin D metabolites sensitively and accurately. Unfortunately, many labs around the world do not take into account the interference caused by epimers. In this review, various methods and techniques for the analysis of C3-epimers are also discussed. The authors believe that C3-epimers may have an important role to play in clinical research, and further research is warranted.

Rat renal 25-hydroxyvitamin D3 1- and 24-hydroxylases: their in vivo regulation

1984 ◽  
Vol 246 (2) ◽  
pp. E168-E173 ◽  
Author(s):  
Y. Tanaka ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Inorganic Phosphorus ◽  
Hydroxylase Activity ◽  
Deficient Diet ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Dietary Phosphorus ◽  
Low Calcium

The effects of thyroparathyroidectomy, parathyroid hormone, 1,25-dihydroxyvitamin D3, dietary calcium, dietary phosphorus, age, and sex on the renal 25-hydroxyvitamin D3 1- and 24-hydroxylases measured in vitro in rats have been studied. Thyroparathyroidectomy of vitamin D-deficient rats abolishes 25-hydroxyvitamin D3 1-hydroxylase activity, and administration of bovine parathyroid extract to the thyroparathyroidectomized rat restores diminished 1-hydroxylase activity. Both suppression and restoration of the enzyme activities require many hours (18-24 h) independent of rapid changes in serum calcium and inorganic phosphorus levels in response to these manipulations. Administration of 1,25-dihydroxyvitamin D3 to vitamin D-deficient rats suppresses 25-hydroxyvitamin D3 1-hydroxylase activity and stimulates 25-hydroxyvitamin D3 24-hydroxylase activity within 48 h. Rats maintained on a low-calcium or a low-phosphorus diet with a daily supplement of 20 IU vitamin D3 show high 25-hydroxyvitamin D3 1-hydroxylase activity and low 24-hydroxylase activity as compared with rats similarly treated but fed a diet containing adequate calcium or adequate phosphorus. When vitamin D-sufficient rats having suppressed renal 25-hydroxyvitamin D3 1-hydroxylase activity are placed on a low-calcium vitamin D-deficient diet for 7 days, the 1-hydroxylase activity is greatly stimulated in 6-wk-old rats but much less so in rats with advancing age.

In Vivo Intestinal Calcium Transport in Infant Rats: Normal and Growth Retarded

1979 ◽  
Vol 109 (4) ◽  
pp. 573-579 ◽  
Author(s):  
M. Kabir Younoszai ◽  
Fayez K. Ghishan
Keyword(s):  
Calcium Transport ◽  
Infant Rats ◽  
Intestinal Calcium Transport

Biological activity of 26,26,26,27,27,27-hexafluoro- 1,25-dihydroxyvitamin D3 in the chick

1989 ◽  
Vol 121 (4) ◽  
pp. 520-524 ◽  
Author(s):  
Takeshi Kiriyama ◽  
Sumiaki Okamoto ◽  
Hiroyuki Suzuki ◽  
Akihiko Nagata ◽  
Motomori Izumi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Biological Activity ◽  
Inorganic Phosphorus ◽  
Binding Ability ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
X Ray ◽  
Dihydroxyvitamin D ◽  
Increased Activity ◽  
Biological Differences

Abstract. A newly synthesized fluorinated analogue of 1,25-dihydroxyvatimin D3 (1,25(OH)2D3), 26,26,26,27,27, 27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25-(OH)2D3) has been compared with 1,25(OH)2D3 as to its biological activity in vitamin D-deficient chicks. One day old, white Leghorn cockerels were fed a rachitogenic diet for 5 weeks. They were then given vehicle or 32.5, 130 or 325 pmol of 26,27-F6-1,25(OH)2D3 or 1,25(OH)2D3 in a solution of propylenglycol:ethanol (95:5 v/v) sc every day for 2 weeks. Twenty-four hours after the last dose, the animals were sacrificed and their femurs were removed. 26,27-F6-1,25(OH)2D3 was more active than 1,25(OH)2D3 in stimulating growth, healing of rachitic cartilage visualized by soft X-ray radiography, elevation of serum inorganic phosphorus, and mineralization of rachitic bone. These biological differences between two compounds were observed only for the dose of 130 pmol. However, this fluorinated compound has less binding ability than 1,25(OH)2D3 to fetal chick intestinal cytosol receptors. The mechanism of the higher potency of this analogue is still unknown, but its affinity to the 1,25(OH)2D3 receptor does not account for the higher activity. Since 26-hydroxylation can be postulated as the inactivation step in vitamin D metabolism, these results suggest that the reason for increased activity of this fluorinated analogue is most likely its slower metabolism.

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