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Record Information
Version2.0
Creation Date2014-08-29 04:49:29 UTC
Update Date2014-12-24 20:26:36 UTC
Accession NumberT3D4029
Identification
Common NameOkadaic acid
ClassSmall Molecule
DescriptionOkadaic acid is found in mollusks. Okadaic acid is found in the marine sponges Halichondria okadai and Halichondria melanodocia and shellfish. It is a metabolite of Prorocentrum lima. It is a diarrhetic shellfish toxin. Okadaic acid is a toxin that accumulates in bivalves and causes diarrhetic shellfish poisoning. The molecular formula of okadaic acid, which is a derivative of a C38 fatty acid, is C44H68O13. The IUPAC name of okadaic acid is (2R)-2-hydroxy-3-{(2S,5R,6R,8S)-5-hydroxy-[(1R,2E)-3-((2R,5R,6'S,8'R,8a'S)-8'-hydroxy-6'-{(1S,3S)-1-hydroxy-3-[(3R,6S)-3-methyl-1,7-dioxaspiro[5.5]undec-2-yl]butyl}-7'-methyleneoctahydro-3H,3'H-spiro[furan-2,2'-pyrano[3,2-b]pyran]-5-yl)-1-methylprop-2-en-1-yl]-10-methyl-1,7-dioxaspiro[5.5]undec-10-en-2-yl}-2-methylpropanoic acid. Okadaic acid was named from the marine sponge Halichondria okadai, from which okadaic acid was isolated for the first time. It has also been isolated from another marine sponge, H. malanodocia, as a cytotoxin. The real producer of okadaic acid is a marine dinoflagellate. Okadaic acid has been shown to exhibit anti-tumor, signalling, apoptotic and lipolytic functions Okadaic acid belongs to the family of Okadaic Acids and Derivatives. These are heat-stable polyether and lipophilic compounds that accumulate in the fatty tissue of shellfish. (1, 2, 3, 4).
Compound Type
  • Animal Toxin
  • Ether
  • Food Toxin
  • Ionophore
  • Marine Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
9,10-Deepithio-9,10-didehydroacanthifolicin
Okadaate
PL toxin II
Chemical FormulaC44H68O13
Average Molecular Mass805.003 g/mol
Monoisotopic Mass804.466 g/mol
CAS Registry Number78111-17-8
IUPAC Name2-hydroxy-3-{5-hydroxy-8-[(3E)-4-[8'-hydroxy-6'-(1-hydroxy-3-{3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl}butyl)-7'-methylidene-hexahydro-3'H-spiro[oxolane-2,2'-pyrano[3,2-b]pyran]-5-yl]but-3-en-2-yl]-10-methyl-1,7-dioxaspiro[5.5]undec-10-en-2-yl}-2-methylpropanoic acid
Traditional Name2-hydroxy-3-{5-hydroxy-8-[(3E)-4-[8'-hydroxy-6'-(1-hydroxy-3-{3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl}butyl)-7'-methylidene-hexahydrospiro[oxolane-2,2'-pyrano[3,2-b]pyran]-5-yl]but-3-en-2-yl]-10-methyl-1,7-dioxaspiro[5.5]undec-10-en-2-yl}-2-methylpropanoic acid
SMILES[H]\C(C(C)C1CC(C)=CC2(OC(CC(C)(O)C(O)=O)CCC2O)O1)=C(\[H])C1CCC2(CCC3OC(C(O)CC(C)C4OC5(CCCCO5)CCC4C)C(=C)C(O)C3O2)O1
InChI IdentifierInChI=1/C44H68O13/c1-25-21-34(55-44(23-25)35(46)12-11-31(54-44)24-41(6,50)40(48)49)26(2)9-10-30-14-18-43(53-30)19-15-33-39(57-43)36(47)29(5)38(52-33)32(45)22-28(4)37-27(3)13-17-42(56-37)16-7-8-20-51-42/h9-10,23,26-28,30-39,45-47,50H,5,7-8,11-22,24H2,1-4,6H3,(H,48,49)/b10-9+
InChI KeyInChIKey=QNDVLZJODHBUFM-MDZDMXLPNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as ketals. These are acetals derived from ketones by replacement of the oxo group by two hydrocarbyloxy groups R2C(OR)2 ( R not Hydrogen ). This term, once abandoned, has been reinstated as a subclass of acetals.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassEthers
Direct ParentKetals
Alternative Parents
Substituents
  • Ketal
  • Alpha-hydroxy acid
  • Hydroxy acid
  • Oxane
  • Pyran
  • Tertiary alcohol
  • Tetrahydrofuran
  • Secondary alcohol
  • Organoheterocyclic compound
  • Oxacycle
  • Monocarboxylic acid or derivatives
  • Dialkyl ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxide
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point164 - 166°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00442 mg/mLALOGPS
logP2.73ALOGPS
logP5.13ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)3.76ChemAxon
pKa (Strongest Basic)-3.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area182.83 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity210.78 m3·mol-1ChemAxon
Polarizability88.49 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-052u-6202012910-6a4e7089c2f900223a19View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-052u-9112168800-6d0bf4b6d501addde97bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pic-9212022100-6bc8f80d6aac5cf74256View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-9302010110-aeb2581b5f1840056f0cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-9017000500-f2952279f3ed70043dc9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0fft-9546110100-b7aa8c44534d446d8d84View in MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityOkadaic acid (OA) dramatically increases both nerve growth factor (NGF) mRNA content (50-fold) and NGF secretion (100-fold) in astrocytes. Okadaic acid also activated NGF gene transcription, which was preceded by an induction of c-fos and c-jun gene transcription. The induction of NGF expression by okadaic acid appeared independent from protein kinase C activity because down-regulating protein kinase C activity failed to decrease the okadaic acid stimulation. Results indicate that okadaic acid profoundly stimulates NGF expression in astrocytes mainly by enhancing NGF mRNA stability and suggest important roles for phosphoprotein phosphatases in regulating NGF production. Instead of activating protein kinase C like the phorbol ester tumor promoters, OA specifically inhibits phosphoprotein phosphatases 1 and 2A leading to an increase in the phosphorylation state of many cellular proteins. Interestingly, OA treatment of fibroblasts mimicked the effects of IL-1 on protein phosphorylation, suggesting that one cellular action of IL-1 might be to inhibit phosphoprotein phosphatase activity. OA has also been found to increase NGF mRNA content in mixed glial-neuronal hippocampal cell cultures similar to IL-1. The toxic potency of this phycotoxin is highly associated with the presence of the free carboxylic acid. Therefore, the toxin forms where the carboxylic acid is acylated are less toxic. However, it is clear that enzymatic hydrolisis after consumption of contaminated shellfish can occur, therefore liberating the free acid. (PMID: 19925818; PMID: 7890729)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesOkadaic acid is found in mollusks. Okadaic acid is found in the marine sponges Halichondria okadai and Halichondria melanodocia and shellfish. It is a diarrhetic shellfish toxin. Okadaic acid is a toxin that accumulates in bivalves and causes diarrhetic shellfish poisoning. Okadaic acid was named from the marine sponge Halichondria okadai, from which okadaic acid was isolated for the first time. It has also been isolated from another marine sponge, H. malanodocia, as a cytotoxin.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB02169
HMDB IDHMDB30441
PubChem Compound ID5353844
ChEMBL IDNot Available
ChemSpider ID4510235
KEGG IDC01945
UniProt IDNot Available
OMIM ID
ChEBI ID1137572
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkOkadaic_acid
References
Synthesis ReferenceNot Available
MSDST3D4029.pdf
General References
  1. Yatsunami J, Komori A, Ohta T, Suganuma M, Fujiki H: Hyperphosphorylation of retinoblastoma protein and p53 by okadaic acid, a tumor promoter. Cancer Res. 1993 Jan 15;53(2):239-41. [8417815 ]
  2. Korhonen P, Kyrylenko S, Suuronen T, Salminen A: Changes in DNA binding pattern of transcription factor YY1 in neuronal degeneration. Neurosci Lett. 2005 Mar 29;377(2):121-4. Epub 2004 Dec 21. [15740849 ]
  3. Di Bartolomeo S, Spinedi A: Potentiation of okadaic acid-induced ceramide elevation but not apoptosis by inhibition of glucosylceramide synthase in human neuroepithelioma cells. Biochem Pharmacol. 2001 Apr 1;61(7):851-6. [11274971 ]
  4. Morimoto C, Kiyama A, Kameda K, Ninomiya H, Tsujita T, Okuda H: Mechanism of the stimulatory action of okadaic acid on lipolysis in rat fat cells. J Lipid Res. 2000 Feb;41(2):199-204. [10681403 ]
  5. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Protein serine/threonine phosphatase activity
Specific Function:
Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).
Gene Name:
PPP1CC
Uniprot ID:
P36873
Molecular Weight:
36983.4 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]