Retinoic acid

For all-trans-retinoic acid as a drug, see Tretinoin. For 9-cis-retinoic acid as a drug, see Alitretinoin. For 13-cis-retinoic acid as a drug, see Isotretinoin.

All-trans-retinoic acid
Skeletal formula of retinoic acid
Ball-and-stick model of the retinoic acid molecule
Names
IUPAC name
Retinoic acid
Systematic IUPAC name
(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
Other names
vitamin A acid; RA
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
UNII
  • InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14+
    Key: SHGAZHPCJJPHSC-YCNIQYBTSA-N
  • CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C/C(=O)O)/C)/C
Properties
C20H28O2
Molar mass 300.442 g·mol−1
Appearance Yellow to light orange crystalline powder with a characteristic of a floral scent[1]
Melting point 180 to 182 °C (356 to 360 °F; 453 to 455 K) Crystals from ethanol[1]
Nearly insoluble
Solubility in fat Soluble
Related compounds
Related compounds
 retinol; retinal; beta-carotene
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 (simplified nomenclature for all-trans-retinoic acid) is a metabolite of vitamin A1 (all-trans-retinol) that is required for embryonic development, male fertility, regulation of bone growth and immune function.[2] All-trans-retinoic acid is required for chordate animal development, which includes all higher animals from fish to humans. During early embryonic development, all-trans-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo.[3] It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages.[4] In adult tissues, the activity of endogenous retinoic acid appears limited to immune function.[2] and male fertility.[5] Retinoic acid administered as a drug (see tretinoin and alitretinoin) causes significant toxicity that is distinct from normal retinoid biology.[6]

All-trans-retinoic acid is the major occurring retinoic acid, while isomers like 13-cis- and 9-cis-retinoic acid are also present in much lower levels.[7]

The key role of all-trans-retinoic acid in embryonic development mediates the high teratogenicity of retinoid pharmaceuticals, such as isotretinoin (13-cis-retinoic acid) used for treatment of acne or retinol used for skin disorders. High oral doses of preformed vitamin A (retinyl palmitate), and all-trans-retinoic acid itself, also have teratogenic potential by this same mechanism.[8]

  1. ^ a b Merck Index, 13th Edition, 8251.
  2. ^ a b Hall JA, Grainger JR, Spencer SP, Belkaid Y (July 2011). "The role of retinoic acid in tolerance and immunity". Immunity. 35 (1): 13–22. doi:10.1016/j.immuni.2011.07.002. PMC 3418663. PMID 21777796.
  3. ^ Duester G (September 2008). "Retinoic acid synthesis and signaling during early organogenesis". Cell. 134 (6): 921–931. doi:10.1016/j.cell.2008.09.002. PMC 2632951. PMID 18805086.
  4. ^ Holland LZ (May 2007). "Developmental biology: a chordate with a difference". Nature. 447 (7141): 153–155. Bibcode:2007Natur.447..153H. doi:10.1038/447153a. PMID 17495912. S2CID 5549210.
  5. ^ Topping T, Griswold MD (2022-04-28). "Global Deletion of ALDH1A1 and ALDH1A2 Genes Does Not Affect Viability but Blocks Spermatogenesis". Frontiers in Endocrinology. 13: 871225. doi:10.3389/fendo.2022.871225. PMC 9097449. PMID 35574006.
  6. ^ Esposito M, Amory JK, Kang Y (September 2024). "The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes". The Journal of Experimental Medicine. 221 (9). doi:10.1084/jem.20240519. PMC 11318670. PMID 39133222.
  7. ^ Rühl R, Krezel W, de Lera AR (December 2018). "9-Cis-13,14-dihydroretinoic acid, a new endogenous mammalian ligand of retinoid X receptor and the active ligand of a potential new vitamin A category: vitamin A5". Nutrition Reviews. 76 (12): 929–941. doi:10.1093/nutrit/nuy057. PMID 30358857.
  8. ^ "PRAC Seeks New Pregnancy Prevention Measures For Retinoids". Medscape. Retrieved 2024-08-15.