Retinoic acid: Difference between revisions
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'''Retinoic acid''' is the oxidized form of [[Vitamin A]] or [[retinol]], with only partial vitamin A function. It plays several essential functions in [[chordates]] during embryonic development including determining position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo.<ref name="Duester">Duester, G. (2008) Retinoic acid synthesis and signaling during early organogenesis. Cell 134: 921-931.</ref> It acts through [[Hox gene]]s, which ultimately control anterior/posterior patterning in early developmental stages. |
'''Retinoic acid''' is the oxidized form of [[Vitamin A]] or [[retinol]], with only partial vitamin A function. It plays several essential functions in [[chordates]] during embryonic development including determining position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo.<ref name="Duester">Duester, G. (2008) Retinoic acid synthesis and signaling during early organogenesis. Cell 134: 921-931. PMCID: [http://www.pubmedcentral.gov/articlerender.fcgi?tool=nihms&artid=2632951 PMC2632951]</ref> It acts through [[Hox gene]]s, which ultimately control anterior/posterior patterning in early developmental stages. |
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<ref name="Holland">{{cite journal |author=Holland, Linda Z. |title=Developmental biology: A chordate with a difference |journal=Nature |volume=447 |issue= 7141|pages=153–155 |year=2007 |doi=10.1038/447153a |pmid=17495912}}</ref> |
<ref name="Holland">{{cite journal |author=Holland, Linda Z. |title=Developmental biology: A chordate with a difference |journal=Nature |volume=447 |issue= 7141|pages=153–155 |year=2007 |doi=10.1038/447153a |pmid=17495912}}</ref> |
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== Retinoic acid function in the absense of precursors retinol or retinaldehyde == |
== Retinoic acid function in the absense of precursors retinol or retinaldehyde == |
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Retinoic acid is responsible for most of the activity of vitamin A, save visual pigment effects which require [[retinal]] (retinaldehyde), and cell metabolism effects that may require [[retinol]] itself. Also, some biochemical functions necessary for fertility in vitamin A deficient male and female mammals |
Retinoic acid is responsible for most of the activity of vitamin A, save visual pigment effects which require [[retinal]] (retinaldehyde), and cell metabolism effects that may require [[retinol]] itself. Also, some biochemical functions necessary for fertility in vitamin A deficient male and female mammals originally appeared to require retinol for rescue, but this is due to a requirement for local conversion of retinol to retinoic acid, as administered retinoic acid does not reach some critical tissues unless given in high amounts. Thus, if animals are fed only retinoic acid but no vitamin A (retinol or retinal), they suffer none of the growth-stunting or epithelial-damaging effects of lack of vitamin A (including no [[xerophthalmia]]-- dryness of the cornea). They do suffer retina degeneration and blindness, due to [[retinal]] (retinaldehyde) deficiency. They also suffer defects in reproducton: vitamin A-deprived but retinoic acid-supplemented male rats exhibit [[hypogonadism]] and [[infertility]] due to lack of local retinoic acid synthesis in the testis; similar treatment of female rats causes infertility due to fetal resorption caused by a lack of local retinoic acid synthesis in the embryo.<ref>http://la.rsmjournals.com/cgi/content/abstract/5/2/239 Lab Anim 1971;5:239-250. The production of experimental vitamin A deficiency in rats and mice. T. Moore and P. D. Holmes. doi:10.1258/002367771781006492.</ref><ref>VanPelt,H.M.M. and DeRooij,D.G.(1991) Spermatogenesis in retinol-deficient rats maintained on retinoic acid. Endocrinology 128,697-704.</ref> |
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==Related pharmaceuticals== |
==Related pharmaceuticals== |
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Revision as of 21:13, 14 September 2010
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| Names | |
|---|---|
| IUPAC name
(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid
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| Other names
vitamin A acid; RA
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| Identifiers | |
3D model (JSmol)
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PubChem CID
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| Properties | |
| C20H28O2 | |
| Molar mass | 300.43512 g/mol |
| Appearance | yellow to light orange crystalline powder with characteristic floral odor [1] |
| Melting point | 180-182 °C, crystals from ethanol [1] |
| nearly insoluble | |
| Solubility in fat | soluble |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Retinoic acid is the oxidized form of Vitamin A or retinol, with only partial vitamin A function. It plays several essential functions in chordates during embryonic development including determining position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo.[2] It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. [3]
Mechanism of biological action
Retinoic acid acts by binding to heterodimers of the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), which then bind to retinoic acid response elements (RAREs) in the regulatory regions of direct target genes (including Hox genes), thereby activating gene transcription. Retinoic acid receptors mediate transcription of different sets of genes of cell differentiation, thus it also depends on the target cells. One of the target genes is the gene of the retinoic acid receptor itself, which occurs during positive regulation.[4]. Control of retinoic acid levels is maintained by a suite of proteins that control synthesis and degradation of retinoic acid.[2][3]
The molecular basis for the interaction between retinoic acid and the Hox genes has been studied by using deletion analysis in transgenic mice carrying constructs of lacZ reporter genes. Such studies have identified functional RAREs within flanking sequences of some of the most 3' Hox genes, suggesting a direct interaction between the genes and retinoic acid. These types of studies strongly support the normal roles of retinoids in patterning vertebrate embryogenesis through the Hox genes.[5]
Biosynthesis
Retinoic acid can be produced in the body by two sequential oxidation steps which convert retinol to retinaldehyde to retinoic acid, but once produced it cannot be reduced again to retinol. The enzymes that generate retinoic acid are known as retinaldehyde dehydrogenases (Raldh1, Raldh2, and Raldh3).[2]
Retinoic acid function in the absense of precursors retinol or retinaldehyde
Retinoic acid is responsible for most of the activity of vitamin A, save visual pigment effects which require retinal (retinaldehyde), and cell metabolism effects that may require retinol itself. Also, some biochemical functions necessary for fertility in vitamin A deficient male and female mammals originally appeared to require retinol for rescue, but this is due to a requirement for local conversion of retinol to retinoic acid, as administered retinoic acid does not reach some critical tissues unless given in high amounts. Thus, if animals are fed only retinoic acid but no vitamin A (retinol or retinal), they suffer none of the growth-stunting or epithelial-damaging effects of lack of vitamin A (including no xerophthalmia-- dryness of the cornea). They do suffer retina degeneration and blindness, due to retinal (retinaldehyde) deficiency. They also suffer defects in reproducton: vitamin A-deprived but retinoic acid-supplemented male rats exhibit hypogonadism and infertility due to lack of local retinoic acid synthesis in the testis; similar treatment of female rats causes infertility due to fetal resorption caused by a lack of local retinoic acid synthesis in the embryo.[6][7]
Related pharmaceuticals
- Tretinoin (Tradename: Retin-A)
- Isotretinoin (Tradename: Accutane(US), Roaccutane)
References
- ^ a b Merck Index, 13th Edition, 8251.
- ^ a b c Duester, G. (2008) Retinoic acid synthesis and signaling during early organogenesis. Cell 134: 921-931. PMCID: PMC2632951
- ^ a b Holland, Linda Z. (2007). "Developmental biology: A chordate with a difference". Nature. 447 (7141): 153–155. doi:10.1038/447153a. PMID 17495912.
- ^ Edgar Wingender (1993). "Steroid/Thyroid Hormone Receptors". Gene Regulation in Eukaryotes. New York: VCH. p. 316. ISBN 1-56081-706-2.
- ^
Marshall, H.; et al. (1996.). "Retinoids and Hox genes" (PDF). The FASEB Journal. 10: 969–978. Retrieved 2009-02-19.
{{cite journal}}: Check date values in:|year=(help); Explicit use of et al. in:|author=(help)CS1 maint: year (link) - ^ http://la.rsmjournals.com/cgi/content/abstract/5/2/239 Lab Anim 1971;5:239-250. The production of experimental vitamin A deficiency in rats and mice. T. Moore and P. D. Holmes. doi:10.1258/002367771781006492.
- ^ VanPelt,H.M.M. and DeRooij,D.G.(1991) Spermatogenesis in retinol-deficient rats maintained on retinoic acid. Endocrinology 128,697-704.