Names | |
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IUPAC name
(3R)-3-[(1R,3aR,4E,7aR)- 4-[(2Z)-2-[(3R,5R)-3,5- Dihydroxy-2-methylene-cyclohexylidene]ethylidene] -7a-methyl-2,3,3a,5,6,7-hexahydro-1H -inden-1-yl]butanoic acid
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Identifiers | |
3D model (
JSmol)
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ChemSpider | |
PubChem
CID
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|
CompTox Dashboard (
EPA)
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|
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Properties | |
C23H34O4 | |
Molar mass | 374.514 |
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
|
Calcitroic acid (1α-hydroxy-23-carboxy-24,25,26,27-tetranorvitamin D3) is a major metabolite of 1α,25-dihydroxyvitamin D3 (calcitriol). [1] Around 1980, scientists first reported the isolation of calcitroic acid from the aqueous extract of radioactively treated animals' livers and intestines. Subsequent researches confirmed calcitroic acid to be a part of enterohepatic circulation. [1] Often synthesized in the liver and kidneys, calcitroic acid is generated in the body after vitamin D is first converted into calcitriol, an intermediate in the fortification of bone through the formation and regulation of calcium in the body. [1] These pathways managed by calcitriol [2] are thought to be inactivated [3] through its hydroxylation by the enzyme CYP24A1, also called calcitriol 24-hydroxylase. [4] Specifically, It is thought to be the major route to inactivate vitamin D metabolites. [3] The hydroxylation and oxidation reactions will yield either calcitroic acid via the C24 oxidation pathway or 1,25(OH2)D3-26,23-lactone via the C23 lactone pathway. [5] However, the only scientifically known formation of calcitroic acid is through an oxidative reaction of the 1ɑ,25-dihydroxy vitamin D3. The positions of C24 and C23 undergo multiple oxidative reactions. Thus, causing the large and small side chains of 1ɑ,25-dihydroxy vitamin D3 to cleave off and form calcitroic acid. [6]
The compound has been prepared in the laboratory. [2]
Hydroxylation and further metabolism of calcitriol in the liver and the kidneys yields calcitroic acid, a water-soluble compound that is excreted in bile. [1]
In case where a higher concentration of this acid is used in vitro, studies determined that calcitroic acid binds to vitamin D receptor (VDR) and induces gene transcription. [1]
There is an x-ray co-crystal structure of calcitroic acid that justifies that the calcitroic acid and vitamin D receptor have agonistic confirmation properties. Calcitroic acid has two side chains, the smaller side chain consists of a hydrogen bond with His333 and a single water molecule. In addition, the longer side chain consists of His333 and His423 interacting with 1,25(OH)2D3. [7]
Names | |
---|---|
IUPAC name
(3R)-3-[(1R,3aR,4E,7aR)- 4-[(2Z)-2-[(3R,5R)-3,5- Dihydroxy-2-methylene-cyclohexylidene]ethylidene] -7a-methyl-2,3,3a,5,6,7-hexahydro-1H -inden-1-yl]butanoic acid
| |
Identifiers | |
3D model (
JSmol)
|
|
ChemSpider | |
PubChem
CID
|
|
CompTox Dashboard (
EPA)
|
|
| |
| |
Properties | |
C23H34O4 | |
Molar mass | 374.514 |
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
|
Calcitroic acid (1α-hydroxy-23-carboxy-24,25,26,27-tetranorvitamin D3) is a major metabolite of 1α,25-dihydroxyvitamin D3 (calcitriol). [1] Around 1980, scientists first reported the isolation of calcitroic acid from the aqueous extract of radioactively treated animals' livers and intestines. Subsequent researches confirmed calcitroic acid to be a part of enterohepatic circulation. [1] Often synthesized in the liver and kidneys, calcitroic acid is generated in the body after vitamin D is first converted into calcitriol, an intermediate in the fortification of bone through the formation and regulation of calcium in the body. [1] These pathways managed by calcitriol [2] are thought to be inactivated [3] through its hydroxylation by the enzyme CYP24A1, also called calcitriol 24-hydroxylase. [4] Specifically, It is thought to be the major route to inactivate vitamin D metabolites. [3] The hydroxylation and oxidation reactions will yield either calcitroic acid via the C24 oxidation pathway or 1,25(OH2)D3-26,23-lactone via the C23 lactone pathway. [5] However, the only scientifically known formation of calcitroic acid is through an oxidative reaction of the 1ɑ,25-dihydroxy vitamin D3. The positions of C24 and C23 undergo multiple oxidative reactions. Thus, causing the large and small side chains of 1ɑ,25-dihydroxy vitamin D3 to cleave off and form calcitroic acid. [6]
The compound has been prepared in the laboratory. [2]
Hydroxylation and further metabolism of calcitriol in the liver and the kidneys yields calcitroic acid, a water-soluble compound that is excreted in bile. [1]
In case where a higher concentration of this acid is used in vitro, studies determined that calcitroic acid binds to vitamin D receptor (VDR) and induces gene transcription. [1]
There is an x-ray co-crystal structure of calcitroic acid that justifies that the calcitroic acid and vitamin D receptor have agonistic confirmation properties. Calcitroic acid has two side chains, the smaller side chain consists of a hydrogen bond with His333 and a single water molecule. In addition, the longer side chain consists of His333 and His423 interacting with 1,25(OH)2D3. [7]