Butenolide (T3D3753)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (17)XML
Targets (17)
Record Information
Version2.0
Creation Date2010-05-13 14:52:29 UTC
Update Date2014-12-24 20:26:29 UTC
Accession NumberT3D3753
Identification
Common NameButenolide
ClassSmall Molecule
DescriptionButenolide is a mycotoxin found in various species of fungi of the genus Fusarium. It can often be found in contaminated agricultural products. Butenolide had been implicated as the causative agent of a livestock mycotoxicosis called “fescue foot”, a peripheral vascular disorder occurring in cattle grazing on tall fescue grass. Butenolide is also one of the mycotoxins which have been considered as a suspected etiological factor for Kaschin-Beck disease (an endemic osteoarthropathy) and Keshan disease (an endemic cardiomyopathy), prevailing in some regions of China, and several studies have also indicated that butenolide can cause cartilage damage. (1, 4)
Compound Type
  • Amide
  • Amine
  • Ester
  • Ether
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
4-acetamido-4-Hydroxy-2-butenoic acid gamma-lactone
4-Acetamido-4-hydroxy-2-butenoic acid-.gamma.-lactone
4-Acetamido-4-hydroxy-2-butenoic acid-gamma-lactone
5-acetamido-2(5)-Furanone
Acetamide, N-(2,5-dihydro-5-oxo-2-furanyl)-, (from Fusarium nivale)
Acetamide, N-(2,5-dihydro-5-oxo-2-furyl)- (8CI)
Acetamido-4-hydroxy-2-butenoic acid-Y-lactone
Chemical FormulaC6H7NO3
Average Molecular Mass141.125 g/mol
Monoisotopic Mass141.043 g/mol
CAS Registry Number16275-44-8
IUPAC NameN-(5-oxo-2,5-dihydrofuran-2-yl)ethanimidic acid
Traditional NameN-(5-oxo-2H-furan-2-yl)ethanimidic acid
SMILESCC(O)=NC1OC(=O)C=C1
InChI IdentifierInChI=1/C6H7NO3/c1-4(8)7-5-2-3-6(9)10-5/h2-3,5H,1H3,(H,7,8)
InChI KeyInChIKey=HUSDLVGPEKVWAL-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as butenolides. These are dihydrofurans with a carbonyl group at the C2 carbon atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDihydrofurans
Sub ClassFuranones
Direct ParentButenolides
Alternative Parents
Substituents
  • 2-furanone
  • Enoate ester
  • Alpha,beta-unsaturated carboxylic ester
  • Carboxylic acid ester
  • Lactone
  • Carboximidic acid
  • Carboximidic acid derivative
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Oxacycle
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility10.7 g/LALOGPS
logP0.74ALOGPS
logP0.7ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)5.56ChemAxon
pKa (Strongest Basic)-0.84ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area58.89 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity33.9 m³·mol⁻¹ChemAxon
Polarizability12.99 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0007-5900000000-71112cefe3108ffd3c162016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-9300000000-e05774f6f0ee6c7fd6802016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udj-9000000000-93e3155c13064ab758e02016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0007-9800000000-6134a48de267a016426a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0f6t-9000000000-febf80a5dd88284bd2dc2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udl-9000000000-e58b5ee3f6870a81e3d02016-08-03View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0006-9000000000-c954a4b07102c8ac0d702014-09-20View Spectrum
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (5)
Mechanism of ToxicityButenolide causes lipid peroxidation, disrupting the membrane lipid bilayer and causing damage to membrane protiens. It also induces production of reactive oxygen species by impairing the activities of complexes I–IV of the mitochondrial respiratory chain, especially in the liver, leading to oxidative stress. In addition, butenolide disrupts the cation gradient by inhibiting the activity of Ca2+/Mg2+-ATPase and Na+/K+-ATPase, likely either as a side effect of lipid peroxidation or by binding to the sulfhydryl groups in the active sites of these enzymes. (1, 2)
MetabolismNot Available
Toxicity ValuesLD50: 44 mg/kg (Intraperitoneal, Mouse) (3) LD50: 275 mg/kg (Oral, Mouse) (3)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesButenolide is a mycotoxin found in various species of fungi of the genus Fusarium. It can often be found in contaminated agricultural products. (1)
Minimum Risk LevelNot Available
Health EffectsButenolide is cardiotoxic and hepatotoxic. Fusarium mycotoxins has been associated with both alimentary toxic aleukia, and esophageal cancer. Consumption of Fusarium mycotoxins-contaminated foodstuffs has also been considered as a suspected etiological factor for Kashin–Beck disease and Keshan disease. (1, 4)
SymptomsButenolide irritates the eyes and skin. It may also cause weight loss and growth retardation. (1, 3)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID27790
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkButenolide
References
Synthesis ReferenceNot Available
MSDST3D3753.pdf
General References
  1. Wang YM, Wang HJ, Peng SQ: In ovo exposure of a Fusarium mycotoxin butenolide induces hepatic and renal oxidative damage in chick embryos, and antioxidants provide protections. Toxicol In Vitro. 2009 Oct;23(7):1354-9. doi: 10.1016/j.tiv.2009.06.028. Epub 2009 Jun 30. [19573587 ]
  2. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
  3. Burmeister HR, Grove MD, Kwolek WF: Moniliformin and butenolide: effect on mice of high-level, long-term oral intake. Appl Environ Microbiol. 1980 Dec;40(6):1142-4. [7458312 ]
  4. Liu JB, Wang YM, Peng SQ, Han G, Dong YS, Yang HY, Yan CH, Wang GQ: Toxic effects of Fusarium mycotoxin butenolide on rat myocardium and primary culture of cardiac myocytes. Toxicon. 2007 Sep 1;50(3):357-64. Epub 2007 May 3. [17603091 ]
  5. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Calcium-transporting ATPase type 2C member 1
General Function:
Signal transducer activity
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.
Gene Name:
ATP2C1
Uniprot ID:
P98194
Molecular Weight:
100576.42 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
2. Calcium-transporting ATPase type 2C member 2
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium.
Gene Name:
ATP2C2
Uniprot ID:
O75185
Molecular Weight:
103186.475 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
3. Plasma membrane calcium-transporting ATPase 1
General Function:
Pdz domain binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
Gene Name:
ATP2B1
Uniprot ID:
P20020
Molecular Weight:
138754.045 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
4. Plasma membrane calcium-transporting ATPase 2
General Function:
Protein c-terminus binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
Gene Name:
ATP2B2
Uniprot ID:
Q01814
Molecular Weight:
136875.18 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
5. Plasma membrane calcium-transporting ATPase 3
General Function:
Pdz domain binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.
Gene Name:
ATP2B3
Uniprot ID:
Q16720
Molecular Weight:
134196.025 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
6. Plasma membrane calcium-transporting ATPase 4
General Function:
Scaffold protein binding
Specific Function:
Calcium/calmodulin-regulated and magnesium-dependent enzyme that catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell (PubMed:8530416). By regulating sperm cell calcium homeostasis, may play a role in sperm motility (By similarity).
Gene Name:
ATP2B4
Uniprot ID:
P23634
Molecular Weight:
137919.03 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
7. Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
General Function:
Protein homodimerization activity
Specific Function:
Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A1
Uniprot ID:
O14983
Molecular Weight:
110251.36 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
8. Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
General Function:
S100 protein binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle.
Gene Name:
ATP2A2
Uniprot ID:
P16615
Molecular Weight:
114755.765 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
9. Sarcoplasmic/endoplasmic reticulum calcium ATPase 3
General Function:
Metal ion binding
Specific Function:
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Gene Name:
ATP2A3
Uniprot ID:
Q93084
Molecular Weight:
113976.23 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
10. Sodium/potassium-transporting ATPase subunit alpha-1
General Function:
Steroid hormone binding
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A1
Uniprot ID:
P05023
Molecular Weight:
112895.01 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
11. Sodium/potassium-transporting ATPase subunit alpha-2
General Function:
Steroid hormone binding
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A2
Uniprot ID:
P50993
Molecular Weight:
112264.385 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
12. Sodium/potassium-transporting ATPase subunit alpha-3
General Function:
Steroid hormone binding
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A3
Uniprot ID:
P13637
Molecular Weight:
111747.51 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
13. Sodium/potassium-transporting ATPase subunit alpha-4
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility.
Gene Name:
ATP1A4
Uniprot ID:
Q13733
Molecular Weight:
114165.44 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
14. Sodium/potassium-transporting ATPase subunit beta-1
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane.Involved in cell adhesion and establishing epithelial cell polarity.
Gene Name:
ATP1B1
Uniprot ID:
P05026
Molecular Weight:
35061.07 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
15. Sodium/potassium-transporting ATPase subunit beta-2
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known.Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.
Gene Name:
ATP1B2
Uniprot ID:
P14415
Molecular Weight:
33366.925 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
16. Sodium/potassium-transporting ATPase subunit beta-3
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.
Gene Name:
ATP1B3
Uniprot ID:
P54709
Molecular Weight:
31512.34 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]
Target Details
17. Sodium/potassium-transporting ATPase subunit gamma
General Function:
Transporter activity
Specific Function:
May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
Gene Name:
FXYD2
Uniprot ID:
P54710
Molecular Weight:
7283.265 Da
References
  1. Wang YM, Peng SQ, Zhou Q, Wang MW, Yan CH, Wang GQ, Yang HY: The oxidative damage of butenolide to isolated erythrocyte membranes. Toxicol In Vitro. 2007 Aug;21(5):863-9. Epub 2007 Feb 28. [17416482 ]