1,25-Dihydroxycholecalciferol: Identification of the Proposed Active Form of Vitamin D3 in the Intestine

@article{Norman1971125DihydroxycholecalciferolIO,
  title={1,25-Dihydroxycholecalciferol: Identification of the Proposed Active Form of Vitamin D3 in the Intestine},
  author={Anthony W. Norman and James F. Myrtle and Ronald J. Miogett and H. George Nowicki and Vincent P. Williams and G. Popja�k},
  journal={Science},
  year={1971},
  volume={173},
  pages={51 - 54}
}
The major polar metabolite of cholecalciferol (vitamin D3) present in chick intestinal mucosa has been chemically characterized by mass spectrometric analysis to have a molecular formula of C27H4403 and a structure of 1,25-dihydroxycholecalciferol. This compound, which is produced in the kidney from 25-hydroxycholecalciferol, has been previously shown to be from 4 to 13 times as active as cholecalciferol in stimulating intestinal calcium transport. 1,25-Dihydroxycholecalciferol (previously… 
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1,25-Dihydroxycholecalciferol: Inhibition of Action in Organ-cultured Intestine by Actinomycin D and α-Amanitin
TLDR
The stimulatory action of vitamin D on intestinal calcium absorption has been much studied following the pioneering work of Nicolaysen and two important proposals arose; first, vitamin D3 must be first converted to 1, 25-dihydroxycholecalciferol (1,25-diOH-CC) before it can act on the intestine; and second, 1, 1925-di OH-CC stimulates intestinal calcium transport directly by an actinomycin D-insensitive process.
The metabolism and mechanism of action of 1,25-dihydroxyvitamin D3.
  • R. Kumar
  • Chemistry, Medicine
    Kidney international
  • 1986
TLDR
The tissue (intestinal tissue) is easily isolated and manipulated and hence, this is an ideal tissue in which to examine the mechanism of divalent cation transport and should help in understanding sterol hormone action.
Calcinogenic factor in Solanum malacoxylon: evidence that it is 1,25-dihydroxyvitamin D3-glycoside.
TLDR
1,25-dihydroxyvitamin D3, the active form of vitamin D, exists in the plant world, and its presence probably accounts for pathologic calcification in grazing animals ingesting Solanum malacoxylon.
1,25-Dihydroxycholecalciferol--a hormonally active form of vitamin D.
Biologic effects of 1,25-dihydroxycholecalciferol (a highly active vitamin D metabolite) in acutely uremic rats.
TLDR
The results indicate that renal conversion of calciferol to a more biologically active form is necessary for the stimulation of intestinal calcium absorption and calcium mobilization from bone, and that 1,25-diOH-CC may bypass a possible defect in vitamin D metabolism in uremia.
Vitamin D 3 -25-hydroxylase: tissue occurrence and apparent lack of regulation.
TLDR
Complementary experiments showing the strict control of the 25-hydroxy-vitamin D 3 -1-hydroxylase enzyme by the vitamin D and calcium status of chicks suggest that the regulation of production of the hormonal form of vitamin D resides almost totally at the level of the kidney 25-Hydroxylation at a slow rate and is not strongly inhibited in the presence of excess product.
Effects of 1,25-dihydroxycholecalciferol on intestinal calcium transport in cortisone-treated rats.
TLDR
The results support the concept that under the conditions of these experiments in the rat the apparent antagonism between glucocorticoids and vitamin D may be due to steroid hormone-related alterations in end organ function that are independent of any direct interaction between the hormone and the vitamin and that cannot be reversed by the vitamin.
Characterization of the metabolites of vitamin D 3 in the chick.
TLDR
The studies confirm earlier conclusions that chick metabolite 4A is identical to the 25-OH-D3 metabolite isolated from pig blood by Blunt, DeLuca and Schnoes and substantiate the previous elucidation of the structure of chick peak 4B as 1,25-diOH- D3 and support its role as the hormonal form of vitamin D.
Influence of disodium ethane-1-hydroxy-1,1-diphosphonate on vitamin D metabolism in rats
TLDR
The change in the renal metabolism of vitamin D in rats treated with a rachitogenic dose of EHDP may be caused by the modifications of the calcium metabolism brought about by the diphosphonate.
Studies on calciferol metabolism. 3. Comparison of species distribution and chromatographic separation of vitamin D metabolites.
TLDR
The presence of metabolites 25-OH-CC and 4B, produced in vivo from vitamin D 3, was detected in chick skeleton, laying hen uterus, and the intestinal mucosa of the chick, rat, rabbit, frog, and monkey.
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References

SHOWING 1-10 OF 19 REFERENCES
Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine.
Abstract A biologically active vitamin D3 metabolite (“peak V metabolite”) more polar than 25-hydroxycholecalciferol has been isolated from chicken intestines in pure form as a…
In vitro production of 25-hydroxycholecalciferol.
TLDR
Investigation of the metabolism of vitamin D3 to its biologically active form, 25-hydroxycholecalciferol, in perfused rat livers and in rat liver homogenates found significant conversion was observed, supporting earlier data which indicate that the liver is the major, if not the only, site of conversion of vitaminD3 to 25-HCC.
Studies on calciferol metabolism. I. Production of vitamin D metabolite 4B from 25-OH-cholecalciferol by kidney homogenates.
TLDR
The kidney appears to be a major site of synthesis of Metabolite 4B, the proposed biologically active form of cholecalciferol in the intestine.
Unique Biosynthesis by Kidney of a Biologically Active Vitamin D Metabolite
TLDR
This work has shown that the tritium deficiency and the greater polarity are compatible with oxygen insertion at carbon 1 of 25-HCC, the major form of the circulating vitamin in blood plasma.
Identification of 1,25-Dihydroxycholecalciferol, a New Kidney Hormone controlling Calcium Metabolism
A vitamin D metabolite, 25-dihydroxycholecalciferol, is further hydroxylated by kidney before acting as a hormone on target tissues. The structure of this kidney metabolite is now described.
A rapidly acting metabolite of vitamin D3.
A vitamin D(3) metabolite in intestine more polar than 25-hydroxy-vitamin D(3)(25-OH D(3)) has been detected by countercurrent distribution. The intestinal metabolite is found also after…
Evidence for the biologically active form of cholecalciferol in the intestine.
TLDR
The kinetics of the appearance of Metabolite 4B in the intestine and its binding to intestinal chromatin are consistent with the lag in the physiological response to cholecalciferol.
Vitamin D: A Cholecalciferol Metabolite Highly Active in Promoting Intestinal Calcium Transport
TLDR
The polar intestinal metabolite greatly shortens this lag, stimulating maximum calcium transport by 9 hours and is a likely candidate for the biologically active form of cholecalciferol in the intestine.
Chromosomal Receptor for A Vitamin D Metabolite
Evidence has been presented for the existence of an acidic protein(s) or protein portion of a more complex molecule which has a high affinity for binding noncovalently a biologically active…
The association of a metabolite of vitamin D3 with intestinal mucosa chromatin in vivo.
TLDR
The time course of appearance of the polar metabolite in the entire intestine parallels the location of radioactivity in the chromatin fraction and is consistent with the lag in the physiological response to vitamin D.
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