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Record Information
Version3.6
Creation Date2007-05-22 17:52:59 UTC
Update Date2016-02-11 01:07:25 UTC
HMDB IDHMDB06218
Secondary Accession NumbersNone
Metabolite Identification
Common Name9-cis-Retinal
DescriptionIn vivo, 9-cis-retinal is formed through oxidation of 9-cis-retinol by cis-retinol dehydrogenase (cRDH). (PMID: 15572038 ). The generation of retinoic acid from retinol is a two-step reaction, with the rate-limiting step being the oxidation of retinol into the intermediate retinaldehyde. Two classes of. unrelated enzymes have been implicated in the oxidation of retinol, the classical cytosolic medium chain alcohol dehydrogenases and recently identified microsomal members of the short chain alcohol dehydrogenase reductase (SDR) superfamily. Further oxidation of the retinaldehyde to the retinoic acid is believed to be catalyzed by several cytosolic aldehyde dehydrogenases. Retinoids are micronutrients required to maintain and promote health of vertebrates. They act physiologically by participating in the visual cycle, in regulating cell differentiation, in embryonic development (PMID: 10893430 ), in maintaining normal reproduction, and in the immune response (PMID: 8882153 ). In non-ocular tissues, the effects of retinoids within the body are mediated through retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which act to regulate gene expression as ligand-dependent transcription factors. The naturally occurring ligands for these nuclear receptors are thought to be all-trans-retinoic acid for RARs and 9-cis-retinoic acid for RXRs (PMID: 10322133 ). While many details of the molecular actions of the RARs and RXRs in regulating gene transcription are understood (PMID: 10418975 ), tissue-specific synthetic pathway(s) of their ligands has not been adequately defined. Nevertheless, the therapeutic efficacy of retinoids, including 9-cis-retinoic acid, is well established in both tissue culture and animal models of breast cancer (PMID: 8825126 , PMID: 12743994 ).
Structure
Thumb
Synonyms
ValueSource
(2E,4E,6Z,8E)-3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenalChEBI
(9cis)-RetinalChEBI
9-C-RetinalChEBI
9-cis-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenalChEBI
9-cis-7,11,13-trans-RetinalChEBI
9-cis-RetinaldehydeChEBI
9-cis-Vitamin a aldehydeChEBI
Isoretinene aChEBI
cis-9-RetinalHMDB
Chemical FormulaC20H28O
Average Molecular Weight284.4357
Monoisotopic Molecular Weight284.214015518
IUPAC Name(2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenal
Traditional Name9-cis-retinal
CAS Registry Number514-85-2
SMILES
C/C(/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C)=C\C=O
InChI Identifier
InChI=1S/C20H28O/c1-16(8-6-9-17(2)13-15-21)11-12-19-18(3)10-7-14-20(19,4)5/h6,8-9,11-13,15H,7,10,14H2,1-5H3/b9-6+,12-11+,16-8-,17-13+
InChI KeyInChIKey=NCYCYZXNIZJOKI-MKOSUFFBSA-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
  • Retinoid skeleton
  • Diterpenoid
  • Enal
  • Alpha,beta-unsaturated aldehyde
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aldehyde
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0042 mg/mLALOGPS
logP6.62ALOGPS
logP4.86ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)-4.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area17.07 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity96.87 m3·mol-1ChemAxon
Polarizability35.08 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Retinol MetabolismSMP00074map00830
Vitamin A DeficiencySMP00336Not Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023842
KNApSAcK IDNot Available
Chemspider ID4940758
KEGG Compound IDC16681
BioCyc IDNot Available
BiGG ID2265509
Wikipedia LinkNot Available
NuGOwiki LinkHMDB06218
Metagene LinkHMDB06218
METLIN IDNot Available
PubChem Compound6436082
PDB IDNot Available
ChEBI ID527124
References
Synthesis ReferenceOstapenko, I. A.; Furaev, V. V. The 9-cis isomerization of all-trans-retinal during in vitro regeneration of visual pigment. Nature (London), New Biology (1973), 243(127), 185-6.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Paik J, Blaner WS, Swisshelm K: Cis-retinol dehydrogenase: 9-cis-retinol metabolism and its effect on proliferation of human MCF7 breast cancer cells. Exp Cell Res. 2005 Feb 1;303(1):183-96. [15572038 ]
  2. Ross SA, McCaffery PJ, Drager UC, De Luca LM: Retinoids in embryonal development. Physiol Rev. 2000 Jul;80(3):1021-54. [10893430 ]
  3. Glass CK: Some new twists in the regulation of gene expression by thyroid hormone and retinoic acid receptors. J Endocrinol. 1996 Sep;150(3):349-57. [8882153 ]
  4. Xu L, Glass CK, Rosenfeld MG: Coactivator and corepressor complexes in nuclear receptor function. Curr Opin Genet Dev. 1999 Apr;9(2):140-7. [10322133 ]
  5. McKenna NJ, Xu J, Nawaz Z, Tsai SY, Tsai MJ, O'Malley BW: Nuclear receptor coactivators: multiple enzymes, multiple complexes, multiple functions. J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):3-12. [10418975 ]
  6. Gottardis MM, Lamph WW, Shalinsky DR, Wellstein A, Heyman RA: The efficacy of 9-cis retinoic acid in experimental models of cancer. Breast Cancer Res Treat. 1996;38(1):85-96. [8825126 ]
  7. Paik J, Blaner WS, Sommer KM, Moe R, Swisshlem K: Retinoids, retinoic acid receptors, and breast cancer. Cancer Invest. 2003 Apr;21(2):304-12. [12743994 ]

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
9-cis-Retinal + NAD + Water → 9-cis-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
9-cis-Retinal + NAD + Water → 9-cis-Retinoic acid + NADH + Hydrogen Iondetails
General function:
Involved in zinc ion binding
Specific function:
Class-III ADH is remarkably ineffective in oxidizing ethanol, but it readily catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione.
Gene Name:
ADH5
Uniprot ID:
P11766
Molecular weight:
39723.945
General function:
Involved in zinc ion binding
Specific function:
Not Available
Gene Name:
ADH1B
Uniprot ID:
P00325
Molecular weight:
39835.17
General function:
Involved in zinc ion binding
Specific function:
Could function in retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation. Medium-chain (octanol) and aromatic (m-nitrobenzaldehyde) compounds are the best substrates. Ethanol is not a good substrate but at the high ethanol concentrations reached in the digestive tract, it plays a role in the ethanol oxidation and contributes to the first pass ethanol metabolism.
Gene Name:
ADH7
Uniprot ID:
P40394
Molecular weight:
41480.985
General function:
Involved in zinc ion binding
Specific function:
Not Available
Gene Name:
ADH1A
Uniprot ID:
P07327
Molecular weight:
39858.37
General function:
Involved in zinc ion binding
Specific function:
Not Available
Gene Name:
ADH6
Uniprot ID:
P28332
Molecular weight:
39072.275
General function:
Involved in zinc ion binding
Specific function:
Not Available
Gene Name:
ADH1C
Uniprot ID:
P00326
Molecular weight:
39867.27
General function:
Secondary metabolites biosynthesis, transport and catabolism
Specific function:
Symmetrically cleaves beta-carotene into two molecules of retinal. The reaction proceeds in three stages, epoxidation of the 15,15'-double bond, hydration of the double bond leading to ring opening, and oxidative cleavage of the diol formed.
Gene Name:
BCMO1
Uniprot ID:
Q9HAY6
Molecular weight:
62636.69
General function:
Involved in oxidoreductase activity
Specific function:
Converts 9-cis-retinal to 9-cis-retinoic acid. Has lower activity towards 13-cis-retinal. Has much lower activity towards all-trans-retinal. Has highest activity with benzaldehyde and decanal (in vitro). Has a preference for NAD, but shows considerable activity with NADP (in vitro)
Gene Name:
ALDH8A1
Uniprot ID:
Q9H2A2
Molecular weight:
53400.9
General function:
Involved in signal transducer activity
Specific function:
Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A and anchors them to the mitochondria or the plasma membrane. Although the physiological relevance between PKA and AKAPS with mitochondria is not fully understood, one idea is that BAD, a proapoptotic member, is phosphorylated and inactivated by mitochondria-anchored PKA. It cannot be excluded too that it may facilitate PKA as well as G protein signal transduction, by acting as an adapter for assembling multiprotein complexes. With its RGS domain, it could lead to the interaction to G-alpha proteins, providing a link between the signaling machinery and the downstream kinase
Gene Name:
AKAP10
Uniprot ID:
O43572
Molecular weight:
73817.5