Calcitroic acid
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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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3D model (JSmol)
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PubChem CID
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CompTox Dashboard (EPA)
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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).
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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]
Metabolism
[edit]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 Vitro
[edit]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]
Structure
[edit]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]
References
[edit]- ^ a b c d e Yu OB, Arnold LA (October 2016). "Calcitroic Acid-A Review". ACS Chemical Biology. 11 (10): 2665–2672. doi:10.1021/acschembio.6b00569. PMC 5074857. PMID 27574921.
- ^ a b Meyer, Daniel; Rentsch, Lara; Marti, Roger (2014). "Efficient and scalable total synthesis of calcitroic acid and its 13C-labeled derivative". RSC Adv. 4 (61): 32327–32334. Bibcode:2014RSCAd...432327M. doi:10.1039/c4ra04322g. ISSN 2046-2069.
- ^ a b Jones G, Prosser DE, Kaufmann M (January 2014). "Cytochrome P450-mediated metabolism of vitamin D". Journal of Lipid Research. 55 (1): 13–31. doi:10.1194/jlr.R031534. PMC 3927478. PMID 23564710.
- ^ Sakaki T, Kagawa N, Yamamoto K, Inouye K (January 2005). "Metabolism of vitamin D3 by cytochromes P450". Frontiers in Bioscience. 10: 119–34. doi:10.2741/1514. PMID 15574355.
- ^ Feldman, David, ed. (November 2017). Biochemistry, physiology and diagnostics. Vitamin D / 4th ed.-in-chief David Feldman (4th ed.). Amsterdam: Elsevier Academic Press. ISBN 978-0-12-809965-0.
- ^ Zimmerman, Duane R.; Reinhardt, Timothy A.; Kremer, Richard; Beitz, Donald C.; Reddy, G.Satyanarayana; Horst, Ronald L. (2001). "Calcitroic Acid Is a Major Catabolic Metabolite in the Metabolism of 1α-Dihydroxyvitamin D2". Archives of Biochemistry and Biophysics. 392 (1): 14–22. doi:10.1006/abbi.2001.2419. ISSN 0003-9861. PMID 11469789.
- ^ Yu, Olivia B.; Webb, Daniel A.; Di Milo, Elliot S.; Mutchie, Tania R.; Teske, Kelly A.; Chen, Taosheng; Lin, Wenwei; Peluso-Iltis, Carole; Rochel, Natacha; Helmstädter, Moritz; Merk, Daniel; Arnold, Leggy A. (2021). "Biological evaluation and synthesis of calcitroic acid". Bioorganic Chemistry. 116: 105310. doi:10.1016/j.bioorg.2021.105310. ISSN 0045-2068. PMC 8592288. PMID 34482171.
| Fat soluble |
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| Water soluble |
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