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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-02-16 11:10:57 UTC
Update Date2018-05-28 17:43:42 UTC
HMDB IDHMDB0001852
Secondary Accession Numbers
  • HMDB01852
Metabolite Identification
Common Nameall-trans-Retinoic acid
Descriptionall-trans-Retinoic acid is an isomer of retinoic acid, the oxidized form of vitamin A. Retinoic acid functions in determining position along embryonic anterior/posterior axis in chordates. It acts through Hox genes, which ultimately controls anterior/posterior patterning in early developmental stages (PMID: 17495912 ). It is an important regulator of gene expression during growth and development, and in neoplasms. As a drug, all-trans-retinoic acid is known as tretinoin. Tretinoin is derived from maternal vitamin A and is essential for normal growth and embryonic development. An excess of tretinoin can be teratogenic. Tretinoin is used in the treatment of psoriasis, acne vulgaris, and several other skin diseases. It has also been approved for use in promyelocytic leukemia (leukemia, promyelocytic, acute).
Structure
Thumb
Synonyms
ValueSource
(all-e)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acidChEBI
3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexene-1-yl)-2,4,6,8-nonatetraenoic acid (ecl)ChEBI
AGN 100335ChEBI
all-(e)-Retinoic acidChEBI
all-trans-beta-Retinoic acidChEBI
all-trans-TretinoinChEBI
all-trans-Vitamin a acidChEBI
all-trans-Vitamin a1 acidChEBI
beta-Retinoic acidChEBI
EudynaChEBI
RenovaChEBI
Retin-aChEBI
Retinoic acidChEBI
Retisol-aChEBI
ro 1-5488ChEBI
SolageChEBI
Stieva-aChEBI
trans-Retinoic acidChEBI
Tretin mChEBI
TretinoinChEBI
VesanoidChEBI
Vitamin a acidChEBI
VitinoinChEBI
(all-e)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoateGenerator
(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoateGenerator
3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexene-1-yl)-2,4,6,8-nonatetraenoate (ecl)Generator
all-(e)-RetinoateGenerator
all-trans-b-RetinoateGenerator
all-trans-b-Retinoic acidGenerator
all-trans-beta-RetinoateGenerator
all-trans-β-retinoateGenerator
all-trans-β-retinoic acidGenerator
b-RetinoateGenerator
b-Retinoic acidGenerator
beta-RetinoateGenerator
β-retinoateGenerator
β-retinoic acidGenerator
RetinoateGenerator
trans-RetinoateGenerator
Tretinoin zinc saltMeSH
trans Retinoic acidMeSH
Acid, all-trans-retinoicMeSH
Salt, tretinoin sodiumMeSH
beta all trans Retinoic acidMeSH
beta-all-trans-Retinoic acidMeSH
Acid, vitamin aMeSH
Potassium salt, tretinoinMeSH
Sodium salt, tretinoinMeSH
Acid, beta-all-trans-retinoicMeSH
all-trans-Retinoic acidMeSH
Retin aMeSH
Tretinoin potassium saltMeSH
Zinc salt, tretinoinMeSH
Acid, retinoicMeSH
Acid, trans-retinoicMeSH
Salt, tretinoin potassiumMeSH
Salt, tretinoin zincMeSH
Tretinoin sodium saltMeSH
all trans Retinoic acidMeSH
Chemical FormulaC20H28O2
Average Molecular Weight300.442
Monoisotopic Molecular Weight300.208930142
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
Traditional Nametretinoin
CAS Registry Number302-79-4
SMILES
C\C(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(/C)=C/C(O)=O
InChI Identifier
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+
InChI KeySHGAZHPCJJPHSC-YCNIQYBTSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassRetinoids
Direct ParentRetinoids
Alternative Parents
Substituents
  • Retinoic acid
  • Diterpenoid
  • Retinoid skeleton
  • Medium-chain fatty acid
  • Branched fatty acid
  • Methyl-branched fatty acid
  • Fatty acyl
  • Unsaturated fatty acid
  • Fatty acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organic oxide
  • Organic oxygen compound
  • Carbonyl group
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point181 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP6.30HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0048 g/LALOGPS
logP5.66ALOGPS
logP5.01ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.79 m³·mol⁻¹ChemAxon
Polarizability36.85 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableView in JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0udi-0009000000-12dbd83959268dee6dbfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-066r-4900000000-31c9262cbbf0bad5b738View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0fsl-9600000000-c6681587f0a9ae7a712eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0uei-0494000000-28e6366fdd47e8ba2117View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-052r-2980000000-3e7fc78de83c23830416View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052r-5900000000-ef4d86f8bcf86959f794View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-052b-0090000000-e07ffb4c1e5c63ab1b59View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-052b-0090000000-a0a8411213bbd2543243View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000i-3690000000-97e6a74798dd69c30ad1View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
  • Nucleus
  • Endoplasmic reticulum
Biospecimen Locations
  • Blood
Tissue Locations
  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Bladder
  • Brain
  • Fibroblasts
  • Intestine
  • Kidney
  • Liver
  • Lung
  • Myelin
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skin
  • Spleen
  • Stratum Corneum
  • Testes
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.20 +/- 0.18 uMAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.0145 +/- 0.0092 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID392618
KEGG Compound IDC00777
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTretinoin
METLIN IDNot Available
PubChem Compound444795
PDB IDREA
ChEBI ID15367
References
Synthesis ReferenceSolladie, Guy; Girardin, Andre. Highly stereoselective synthesis of vitamin A and all-trans retinoic acid by low-valent titanium induced reductive elimination. Tetrahedron Letters (1988), 29(2), 213-16.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Czernik PJ, Little JM, Barone GW, Raufman JP, Radominska-Pandya A: Glucuronidation of estrogens and retinoic acid and expression of UDP-glucuronosyltransferase 2B7 in human intestinal mucosa. Drug Metab Dispos. 2000 Oct;28(10):1210-6. [PubMed:10997942 ]
  2. Barua AB, Olson JA: Retinoyl beta-glucuronide: an endogenous compound of human blood. Am J Clin Nutr. 1986 Apr;43(4):481-5. [PubMed:3962900 ]
  3. Napoli JL, Posch KP, Fiorella PD, Boerman MH: Physiological occurrence, biosynthesis and metabolism of retinoic acid: evidence for roles of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) in the pathway of retinoic acid homeostasis. Biomed Pharmacother. 1991;45(4-5):131-43. [PubMed:1932598 ]
  4. Giannini G, Di Marcotullio L, Ristori E, Zani M, Crescenzi M, Scarpa S, Piaggio G, Vacca A, Peverali FA, Diana F, Screpanti I, Frati L, Gulino A: HMGI(Y) and HMGI-C genes are expressed in neuroblastoma cell lines and tumors and affect retinoic acid responsiveness. Cancer Res. 1999 May 15;59(10):2484-92. [PubMed:10344762 ]
  5. Lee YF, Bao BY, Chang C: Modulation of the retinoic acid-induced cell apoptosis and differentiation by the human TR4 orphan nuclear receptor. Biochem Biophys Res Commun. 2004 Oct 22;323(3):876-83. [PubMed:15381082 ]
  6. Mercader J, Ribot J, Murano I, Felipe F, Cinti S, Bonet ML, Palou A: Remodeling of white adipose tissue after retinoic acid administration in mice. Endocrinology. 2006 Nov;147(11):5325-32. Epub 2006 Jul 13. [PubMed:16840543 ]
  7. Natsume N, Kondo S, Matsuyama Y, Sumida K, Inou H, Kawakami N, Sandell LJ, Iwata H: Analysis of cartilage-derived retinoic acid-sensitive protein in cerebrospinal fluid From patients With spinal diseases. Spine (Phila Pa 1976). 2001 Jan 15;26(2):157-60. [PubMed:11154535 ]
  8. Baron JM, Heise R, Blaner WS, Neis M, Joussen S, Dreuw A, Marquardt Y, Saurat JH, Merk HF, Bickers DR, Jugert FK: Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53. [PubMed:15982314 ]
  9. Paez-Pereda M, Kovalovsky D, Hopfner U, Theodoropoulou M, Pagotto U, Uhl E, Losa M, Stalla J, Grubler Y, Missale C, Arzt E, Stalla GK: Retinoic acid prevents experimental Cushing syndrome. J Clin Invest. 2001 Oct;108(8):1123-31. [PubMed:11602619 ]
  10. Saito S, Kondo S, Mishima S, Ishiguro N, Hasegawa Y, Sandell LJ, Iwata H: Analysis of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid from patients with osteoarthritis and rheumatoid arthritis. J Bone Joint Surg Br. 2002 Sep;84(7):1066-9. [PubMed:12358374 ]
  11. Meyer E, Lambert WE, De Leenheer AP: Simultaneous determination of endogenous retinoic acid isomers and retinol in human plasma by isocratic normal-phase HPLC with ultraviolet detection. Clin Chem. 1994 Jan;40(1):48-57. [PubMed:8287543 ]
  12. Masgrau-Peya E, Salomon D, Saurat JH, Meda P: In vivo modulation of connexins 43 and 26 of human epidermis by topical retinoic acid treatment. J Histochem Cytochem. 1997 Sep;45(9):1207-15. [PubMed:9283608 ]
  13. Lopez-Boado YS, Klaus M, Dawson MI, Lopez-Otin C: Retinoic acid-induced expression of apolipoprotein D and concomitant growth arrest in human breast cancer cells are mediated through a retinoic acid receptor RARalpha-dependent signaling pathway. J Biol Chem. 1996 Dec 13;271(50):32105-11. [PubMed:8943263 ]
  14. Stewart ME, Benoit AM, Downing DT, Strauss JS: Suppression of sebum secretion with 13-cis-retinoic acid: effect on individual skin surface lipids and implications for their anatomic origin. J Invest Dermatol. 1984 Jan;82(1):74-8. [PubMed:6228612 ]
  15. Tse HK, Leung MB, Woolf AS, Menke AL, Hastie ND, Gosling JA, Pang CP, Shum AS: Implication of Wt1 in the pathogenesis of nephrogenic failure in a mouse model of retinoic acid-induced caudal regression syndrome. Am J Pathol. 2005 May;166(5):1295-307. [PubMed:15855632 ]
  16. Patel JB, Huynh CK, Handratta VD, Gediya LK, Brodie AM, Goloubeva OG, Clement OO, Nanne IP, Soprano DR, Njar VC: Novel retinoic acid metabolism blocking agents endowed with multiple biological activities are efficient growth inhibitors of human breast and prostate cancer cells in vitro and a human breast tumor xenograft in nude mice. J Med Chem. 2004 Dec 30;47(27):6716-29. [PubMed:15615521 ]
  17. Thiboutot D, Martin P, Volikos L, Gilliland K: Oxidative activity of the type 2 isozyme of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) predominates in human sebaceous glands. J Invest Dermatol. 1998 Sep;111(3):390-5. [PubMed:9740229 ]
  18. Holland LZ: Developmental biology: a chordate with a difference. Nature. 2007 May 10;447(7141):153-5. [PubMed:17495912 ]

Only showing the first 10 proteins. There are 59 proteins in total.

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Binds free retinal and cellular retinol-binding protein-bound retinal. Can convert/oxidize retinaldehyde to retinoic acid (By similarity).
Gene Name:
ALDH1A1
Uniprot ID:
P00352
Molecular weight:
54861.44
Reactions
Retinal + NAD + Water → all-trans-Retinoic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Does metabolize octanal and decanal but does not metabolize citral, benzaldehyde, acetaldehyde and propanal efficiently (By similarity).
Gene Name:
ALDH1A2
Uniprot ID:
O94788
Molecular weight:
54672.24
Reactions
Retinal + NAD + Water → all-trans-Retinoic acid + NADH + Hydrogen Iondetails
General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity toward prostaglandins A1 and E1. Oxidizes arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE).
Gene Name:
CYP4A11
Uniprot ID:
Q02928
Molecular weight:
59347.31
Reactions
all-trans-Retinoic acid + NADPH + Hydrogen Ion + Oxygen → all-trans-18-Hydroxyretinoic acid + NADP + Waterdetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme has glucuronidating capacity with steroid substrates such as 5-beta-androstane 3-alpha,17-beta-diol, estradiol, ADT, eugenol and bile acids. Only isoform 1 seems to be active.
Gene Name:
UGT2B28
Uniprot ID:
Q9BY64
Molecular weight:
38742.9
Reactions
all-trans-Retinoic acid + Uridine diphosphate glucuronic acid → Retinoyl b-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as estriol, 4-hydroxyestrone and 2-hydroxyestriol) and xenobiotics (such as 4-methylumbelliferone, 1-naphthol, 4-nitrophenol, 2-aminophenol, 4-hydroxybiphenyl and menthol). It is capable of 6 alpha-hydroxyglucuronidation of hyodeoxycholic acid.
Gene Name:
UGT2B4
Uniprot ID:
P06133
Molecular weight:
60512.035
Reactions
all-trans-Retinoic acid + Uridine diphosphate glucuronic acid → Retinoyl b-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate.
Gene Name:
UGT1A4
Uniprot ID:
P22310
Molecular weight:
60024.535
Reactions
all-trans-Retinoic acid + Uridine diphosphate glucuronic acid → Retinoyl b-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT2B10
Uniprot ID:
P36537
Molecular weight:
60773.485
Reactions
all-trans-Retinoic acid + Uridine diphosphate glucuronic acid → Retinoyl b-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).
Gene Name:
UGT2B7
Uniprot ID:
P16662
Molecular weight:
60720.15
Reactions
all-trans-Retinoic acid + Uridine diphosphate glucuronic acid → Retinoyl b-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xenobiotic substrates, including simple phenolic compounds, 7-hydroxylated coumarins, flavonoids, anthraquinones, and certain drugs and their hydroxylated metabolites. It also catalyzes the glucuronidation of endogenous estrogens and androgens.
Gene Name:
UGT2B15
Uniprot ID:
P54855
Molecular weight:
61035.815
Reactions
all-trans-Retinoic acid + Uridine diphosphate glucuronic acid → Retinoyl b-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Active on odorants and seems to be involved in olfaction; it could help clear lipophilic odorant molecules from the sensory epithelium.
Gene Name:
UGT2A1
Uniprot ID:
Q9Y4X1
Molecular weight:
60771.605
Reactions
all-trans-Retinoic acid + Uridine diphosphate glucuronic acid → Retinoyl b-glucuronide + Uridine 5'-diphosphatedetails

Transporters

General function:
Involved in binding
Specific function:
Cytosolic CRABPs may regulate the access of retinoic acid to the nuclear retinoic acid receptors
Gene Name:
CRABP1
Uniprot ID:
P29762
Molecular weight:
15565.4
General function:
Involved in binding
Specific function:
Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors
Gene Name:
CRABP2
Uniprot ID:
P29373
Molecular weight:
15692.9

Only showing the first 10 proteins. There are 59 proteins in total.