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Record Information
Version2.0
Creation Date2009-11-13 22:25:18 UTC
Update Date2014-12-24 20:26:13 UTC
Accession NumberT3D3605
Identification
Common NameOchratoxin A
ClassSmall Molecule
DescriptionOchratoxin A is found in barley. Mycotoxin. Ochratoxin A is produced by Aspergillus melleus, Aspergillus sulphureus and Penicillium viridicatum.Potential contaminant of foodstuffs, especially cereals. Ochratoxin A is found in stored grain products in UK (1997).Ochratoxin A, a toxin produced by Aspergillus ochraceus and Penicillium verrucosum, is one of the most abundant food-contaminating mycotoxins in the world. Human exposure occurs mainly through consumption of improperly stored food products, particularly contaminated grain and pork products, as well as coffee, wine grapes and dried grapes. The toxin has been found in the tissues and organs of animals, including human blood and breast milk. Ochratoxin A toxicity has large species- and sex-specific differences. Ochratoxin a belongs to the family of Ochratoxins and related substances. These are compounds containing the ochratoxin skeleton, which is structurally characterized by the presence of a 3-phenylpropanoic acid N-linked to a 8-hydroxy-3-methyl-1-oxo-3,4-dihydro-1H-2-benzopyran-7-carboxamide moiety[1]. (Reference: [1] http://www.inchem.org/documents/ehc/ehc/ehc105.htm).
Compound Type
  • Amide
  • Amine
  • Ester
  • Ether
  • Food Toxin
  • Fungal Toxin
  • Metabolite
  • Mycotoxin
  • Natural Compound
  • Organic Compound
  • Organochloride
Chemical Structure
Thumb
Synonyms
Synonym
Antibiotic 9663
N-[(5-Chloro-3,4-dihydro-8-hydroxy-3-methyl-1-oxo-1H-2-benzopyran-7-yl)carbonyl]phenylalanine, 9CI
Ochratoxin a
Ochratoxin a-bsa conjugate from aspergillus ochraceus
OTA
Phenylalanine - ochratoxin a
Chemical FormulaC20H18ClNO6
Average Molecular Mass403.813 g/mol
Monoisotopic Mass403.082 g/mol
CAS Registry Number303-47-9
IUPAC Name2-{[(5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-1H-2-benzopyran-7-yl)(hydroxy)methylidene]amino}-3-phenylpropanoic acid
Traditional Name2-{[(5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-2-benzopyran-7-yl)(hydroxy)methylidene]amino}-3-phenylpropanoic acid
SMILESCC1CC2=C(Cl)C=C(C(O)=NC(CC3=CC=CC=C3)C(O)=O)C(O)=C2C(=O)O1
InChI IdentifierInChI=1/C20H18ClNO6/c1-10-7-12-14(21)9-13(17(23)16(12)20(27)28-10)18(24)22-15(19(25)26)8-11-5-3-2-4-6-11/h2-6,9-10,15,23H,7-8H2,1H3,(H,22,24)(H,25,26)
InChI KeyInChIKey=RWQKHEORZBHNRI-UHFFFAOYNA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as ochratoxins and related substances. These are a group of chemically related metabolites containing a 3,4-dihydro-3-methylisocoumarin moiety linked through a carboxyl group to L-beta-phenylalanine by a secondary amine bond.
KingdomChemical entities
Super ClassOrganic compounds
ClassPhenylpropanoids and polyketides
Sub ClassOchratoxins and related substances
Direct ParentOchratoxins and related substances
Alternative Parents
Substituents
  • Ochratoxin-skeleton
  • Phenylalanine or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • 3-phenylpropanoic-acid
  • Alpha-amino acid or derivatives
  • Amphetamine or derivatives
  • Benzopyran
  • Isochromane
  • Salicylic acid or derivatives
  • 2-benzopyran
  • Halobenzoic acid or derivatives
  • 3-halobenzoic acid or derivatives
  • Aryl chloride
  • Dicarboxylic acid or derivatives
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl halide
  • Vinylogous acid
  • Carboxamide group
  • Carboxylic acid ester
  • Secondary carboxylic acid amide
  • Lactone
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organoheterocyclic compound
  • Oxacycle
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic 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 RolesNot Available
Physical Properties
StateSolid
AppearanceCrystals from xylene. Exhibits green fluorescence. (5)
Experimental Properties
PropertyValue
Melting Point169°C
Boiling PointNot Available
SolubilityNot Available
LogP4.74
Predicted Properties
PropertyValueSource
Water Solubility0.0256 mg/mLALOGPS
logP3.66ALOGPS
logP5.43ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)3.26ChemAxon
pKa (Strongest Basic)0.14ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area116.42 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity102.29 m3·mol-1ChemAxon
Polarizability39.19 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
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, Positivesplash10-0zfr-5328900000-bb6ff8935be11e6eba85View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-053l-2259000000-f59d898f61dc363b9df8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9410000000-3d2f33580d5bdfc5b412View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0pb9-0019500000-d12f604ac4aad770e948View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-114i-1449200000-49a8c330112595e2a6a7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9220000000-9315be65c28edeb93241View in MoNA
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (4)
Mechanism of ToxicityOchratoxin A has been shown to be weakly mutagenic, possibly by induction of oxidative DNA damage. The nephrotoxin ochratoxin A (OTA) causes a reduction of glomerular filtration rate (GFR) and of para-aminohippuric acid (PAH) clearance. It is a nephrotoxin which blocks plasma membrane anion conductance in Madin-Darby canine kidney (MDCK) cells. Some cytochrome P-450 enzymes, such as CYP2C9, are known to metabolize ochratoxin A into more cytotoxic compounds capable of forming DNA adducts. (6, 3)
MetabolismOchratoxin A is cleaved into phenylalanine and a less toxic iso-coumarin derivative (ochratoxin alpha) by the microbial flora of the colon, and by carboxypeptidase A and alpha-chymotrypsim. This is is the major metabolic pathway. 4-Hydroxyochratoxin A is the main hepatic metabolite and its formation appears to be via a polymorphic-like debrisoquine 4-hydroxylation. Some cytochrome P-450 enzymes, such as CYP2C9, and known to metabolize ochratoxin A into more cytotoxic compounds. (9, 1, 3)
Toxicity ValuesLD50: 20 mg/kg (Oral, Rat) (7) LD50: 12,600 ug/kg (Intraperitoneal, Rat) (7) LD50: 12,750 ug/kg (Intravenous, Rat ) (7) LD50: 46 mg/kg (Oral, Mouse) (7)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (14)
Uses/SourcesHuman exposure occurs mainly through consumption of improperly stored food products, particularly contaminated grain and pork products, as well as coffee, wine grapes and dried grapes. (15)
Minimum Risk LevelNot Available
Health EffectsOchratoxin exposure has been associated with acute tubular necrosis and Balkan endemic nephropathy. Ochratoxin A has been shown to be nephrotoxic and might delay sexual maturation. It can cause immunosuppression and immunotoxicity in animals. It's immunosuppressant activity in animals may include depressed antibody responses, reduced size of immune organs (such as the thymus, spleen, and lymph nodes), changes in immune cell number and function, and altered cytokine production. Immunotoxicity probably results from cell death following apoptosis and necrosis, in combination with slow replacement of affected immune cells due to inhibition of protein synthesis. (8, 15)
SymptomsMight cause respiratory irritation. (8)
TreatmentCare is symptomatic and supportive. (8)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB29399
PubChem Compound ID442530
ChEMBL IDNot Available
ChemSpider ID390954
KEGG IDC09955
UniProt IDNot Available
OMIM ID
ChEBI ID7719
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkOchratoxin_A
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Galtier P: Pharmacokinetics of ochratoxin A in animals. IARC Sci Publ. 1991;(115):187-200. [1820333 ]
  2. Hietanen E, Bartsch H, Bereziat JC, Castegnaro M, Michelon J: Characterization of the cytochrome P450 isozyme that metabolizes ochratoxin A, using metabolic inducers, inhibitors and antibodies. IARC Sci Publ. 1991;(115):297-304. [1820345 ]
  3. Simarro Doorten AY, Bull S, van der Doelen MA, Fink-Gremmels J: Metabolism-mediated cytotoxicity of ochratoxin A. Toxicol In Vitro. 2004 Jun;18(3):271-7. [15046773 ]
  4. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  5. Rothenberg SP, Marcoullis GP, Schwarz S, Lader E: Measurement of cyanocobalamin in serum by a specific radioimmunoassay. J Lab Clin Med. 1984 Jun;103(6):959-72. [6726060 ]
  6. Gekle M, Silbernagl S: Mechanism of ochratoxin A-induced reduction of glomerular filtration rate in rats. J Pharmacol Exp Ther. 1993 Oct;267(1):316-21. [8229758 ]
  7. Begley JA, Colligan PD, Chu RC: Transcobalamin II mediated delivery of albumin-bound hydroxocobalamin to human liver cells. Proc Soc Exp Biol Med. 1993 Nov;204(2):206-10. [8415778 ]
  8. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [15509185 ]
  9. IARC (1983). Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-Present. (Multivolume work).
  10. Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2010; CCIS Volume 143, edition expires Feb, 2010. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2010; CCIS Volume 143, edition expires Feb, 2010.
  11. O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1209
  12. Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 779
  13. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  14. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  15. Wikipedia. Ochratoxin A. Last Updated 26 February 2010. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Simarro Doorten AY, Bull S, van der Doelen MA, Fink-Gremmels J: Metabolism-mediated cytotoxicity of ochratoxin A. Toxicol In Vitro. 2004 Jun;18(3):271-7. [15046773 ]
2. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Simarro Doorten AY, Bull S, van der Doelen MA, Fink-Gremmels J: Metabolism-mediated cytotoxicity of ochratoxin A. Toxicol In Vitro. 2004 Jun;18(3):271-7. [15046773 ]
General Function:
Phosphoenolpyruvate carboxykinase (gtp) activity
Specific Function:
Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.
Gene Name:
PCK1
Uniprot ID:
P35558
Molecular Weight:
69193.975 Da
References
  1. Meisner H, Meisner P: Ochratoxin A, an in vivo inhibitor of renal phosphoenolpyruvate carboxykinase. Arch Biochem Biophys. 1981 Apr 15;208(1):146-53. [7259174 ]
General Function:
Ubiquinone binding
Specific Function:
Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Gene Name:
SDHD
Uniprot ID:
O14521
Molecular Weight:
17042.82 Da
References
  1. Wei YH, Lu CY, Lin TN, Wei RD: Effect of ochratoxin A on rat liver mitochondrial respiration and oxidative phosphorylation. Toxicology. 1985 Aug;36(2-3):119-30. [2996181 ]
General Function:
Ubiquinone binding
Specific Function:
Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Gene Name:
SDHB
Uniprot ID:
P21912
Molecular Weight:
31629.365 Da
References
  1. Wei YH, Lu CY, Lin TN, Wei RD: Effect of ochratoxin A on rat liver mitochondrial respiration and oxidative phosphorylation. Toxicology. 1985 Aug;36(2-3):119-30. [2996181 ]