T3DB: Moniliformin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (7)XML

Targets (7)

Record Information

Version

2.0

Creation Date

2010-05-25 14:32:14 UTC

Update Date

2014-12-24 20:26:31 UTC

Accession Number

T3D3770

Identification

Common Name

Moniliformin

Class

Small Molecule

Description

Moniliformin is a mycotoxin produced by a number of fungi of the Fusarium species. It can by found in contaminated cereal crops and is known to be a lethal food contaminant to fowl as well as a cause of Kashin-Beck disease in humans. (7, 2)

Compound Type

Carbamate
Food Toxin
Fungal Toxin
Mycotoxin
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
1-Hydroxy-cyclobut-1-ene-3,4-dione
3-Hydroxy-3-cyclobutene-1,2-dione
3-Hydroxy-3-cyclobutenedione
Hydroxycyclobutenedione
Semisquaric acid

Chemical Formula

C₄H₂O₃

Average Molecular Mass

98.057 g/mol

Monoisotopic Mass

98.000 g/mol

CAS Registry Number

71376-34-6

IUPAC Name

3-hydroxycyclobut-3-ene-1,2-dione

Traditional Name

moniliformin

SMILES

OC1=CC(=O)C1=O

InChI Identifier

InChI=1S/C4H2O3/c5-2-1-3(6)4(2)7/h1,5H

InChI Key

InChIKey=KGPQKNJSZNXOPV-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as vinylogous acids. These are organic compounds containing a hydroxyl group, which is indirectly attached to a carbonyl via an intervening vinyl (>C=C<) moiety.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Vinylogous acids

Sub Class

Not Available

Direct Parent

Vinylogous acids

Alternative Parents

Substituents

Vinylogous acid
Cyclic ketone
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	158°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	150 g/L	ALOGPS
logP	-0.21	ALOGPS
logP	0.28	ChemAxon
logS	0.19	ALOGPS
pKa (Strongest Acidic)	6.32	ChemAxon
pKa (Strongest Basic)	-5	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	54.37 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	22.83 m³·mol⁻¹	ChemAxon
Polarizability	8.09 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0002-9000000000-bee8fab3a03c257d35ba	2021-09-23	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-04	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-04	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-0006-9000000000-74527f2fd30ebf4007ab	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-9000000000-815d20e946ab89d060fb	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00kb-9000000000-d658971bcdfc4832f2b1	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-1a20f0ba8a130bdd7756	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-9000000000-0b4c42c4195ca5523e92	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0005-9000000000-90d030c8ccc394671fd6	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0007-9000000000-4a5123231f3b3564f568	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0007-9000000000-ad152969e2985e58d200	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9000000000-3166a519aff91bfd5c6e	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-6ffb9541e24882de3fac	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-10-25	View Spectrum

Toxicity Profile

Route of Exposure

Oral, dermal, inhalation, and parenteral (contaminated drugs). (5)

Mechanism of Toxicity

Moniliformin reversibly inhibits the enzymes pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase by competing for the binding site of pyruvate. This interferes with the tricarboxylic acid cycle by preventing the necessary incorporation of pyruvate and oxidation of the alpha-ketoglutarate intermediate. Moniliformin has also been shown to interfere with carbohydrate metabolism by inhibiting transketolase and aldose reductase. Moniliformin causes the necrosis of human chondrocytes in cartilage. It does so by increasing the expression of matrix catabolic enzymes, such as MMP-1 and MMP-13, and decreasing the syntheses of extracellular matrix components such as aggrecan and type II collage. This accelerates the catabolism of the extracellular matrix in articular cartilages, inducing a loss of cartilage function and eventually leading to cartilage degradation. Moniliformin is also known to cause DNA damage, inducing chromatid breaks, chromosome breaks, and chromatid exchanges. (2, 3, 4)

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

LD50: 20.9 mg/kg (Mouse, Intraperitoneal) (4)

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Moniliformin is a mycotoxin produced by a number of fungi of the Fusarium species. It can by found in contaminated cereal crops. (7, 2)

Minimum Risk Level

Not Available

Health Effects

Moniliformin is believed to be a cause of Kashin-Beck disease, which causes joint destruction and deformity. It may also have immunosuppressive properties and can cause fungal infections such as mycotic keratitis. (1, 2, 3, 8)

Symptoms

The main symptoms of acute moniliformin toxication in animals are muscular weakness, respiratory stress, myocardial degeneration, as well as some histopathological changes in organs such as the kidneys, the lungs and the pancreas, followed by coma and death. Kashin-Beck disease is characterized by joint pain, with restriction of movement and joint enlargement. (4)

Treatment

Kashin-Beck disease cannot be cured but can be treated with physical therapy and corrective surgery. Natamycin ophthalmic suspension is the drug of choice for filamentous fungal infections such as mycotic keratitis. (6, 9)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

40452

ChEMBL ID

Not Available

ChemSpider ID

Not Available

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Moniliformin

References

Synthesis Reference

Not Available

MSDS

T3D3770.pdf

General References

Naiker S, Odhav B: Mycotic keratitis: profile of Fusarium species and their mycotoxins. Mycoses. 2004 Feb;47(1-2):50-6. [14998400 ]
Zhang A, Cao JL, Yang B, Chen JH, Zhang ZT, Li SY, Fu Q, Hugnes CE, Caterson B: Effects of moniliformin and selenium on human articular cartilage metabolism and their potential relationships to the pathogenesis of Kashin-Beck disease. J Zhejiang Univ Sci B. 2010 Mar;11(3):200-8. doi: 10.1631/jzus.B0900074. [20205306 ]
Celik M, Yilmaz S, Aksoy H, Unal F, Yuzbasioglu D, Donbak L: Evaluation of the genotoxicity of Fusarium mycotoxin moniliformin in human peripheral blood lymphocytes. Environ Mol Mutagen. 2009 Jun;50(5):431-4. doi: 10.1002/em.20459. [19230001 ]
Jestoi M: Emerging fusarium-mycotoxins fusaproliferin, beauvericin, enniatins, and moniliformin: a review. Crit Rev Food Sci Nutr. 2008 Jan;48(1):21-49. doi: 10.1080/10408390601062021. [18274964 ]
Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
Wikipedia. Fungal Keratitis. Last Updated 26 March 2010. [Link]
Wikipedia. Moniliformin. Last Updated 7 July 2009. [Link]
Wikipedia. Kashin-Beck disease. Last Updated 4 May 2010. [Link]
Wikipedia. Iron. Last Updated 29 July 2009. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 2-oxoglutarate dehydrogenase, mitochondrial

General Function:: Thiamine pyrophosphate binding
Specific Function:: The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). It contains multiple copies of three enzymatic components: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3).
Gene Name:: OGDH
Uniprot ID:: Q02218
Molecular Weight:: 115934.37 Da

References

Jestoi M: Emerging fusarium-mycotoxins fusaproliferin, beauvericin, enniatins, and moniliformin: a review. Crit Rev Food Sci Nutr. 2008 Jan;48(1):21-49. doi: 10.1080/10408390601062021. [18274964 ]
Gathercole PS, Thiel PG, Hofmeyr JH: Inhibition of pyruvate dehydrogenase complex by moniliformin. Biochem J. 1986 Feb 1;233(3):719-23. [3707519 ]
Pirrung MC, Nauhaus SK, Singh B: Cofactor-Directed, Time-Dependent Inhibition of Thiamine Enzymes by the Fungal Toxin Moniliformin. J Org Chem. 1996 Apr 19;61(8):2592-2593. [11667082 ]

Target Details

2. Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

General Function:: Pyruvate dehydrogenase activity
Specific Function:: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:: PDHA1
Uniprot ID:: P08559
Molecular Weight:: 43295.255 Da

References

Jestoi M: Emerging fusarium-mycotoxins fusaproliferin, beauvericin, enniatins, and moniliformin: a review. Crit Rev Food Sci Nutr. 2008 Jan;48(1):21-49. doi: 10.1080/10408390601062021. [18274964 ]
Gathercole PS, Thiel PG, Hofmeyr JH: Inhibition of pyruvate dehydrogenase complex by moniliformin. Biochem J. 1986 Feb 1;233(3):719-23. [3707519 ]

Target Details

3. Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial

General Function:: Pyruvate dehydrogenase (acetyl-transferring) activity
Specific Function:: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:: PDHA2
Uniprot ID:: P29803
Molecular Weight:: 42932.855 Da

References

Jestoi M: Emerging fusarium-mycotoxins fusaproliferin, beauvericin, enniatins, and moniliformin: a review. Crit Rev Food Sci Nutr. 2008 Jan;48(1):21-49. doi: 10.1080/10408390601062021. [18274964 ]
Gathercole PS, Thiel PG, Hofmeyr JH: Inhibition of pyruvate dehydrogenase complex by moniliformin. Biochem J. 1986 Feb 1;233(3):719-23. [3707519 ]

Target Details

4. Pyruvate dehydrogenase E1 component subunit beta, mitochondrial

General Function:: Pyruvate dehydrogenase activity
Specific Function:: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:: PDHB
Uniprot ID:: P11177
Molecular Weight:: 39233.1 Da

References

Jestoi M: Emerging fusarium-mycotoxins fusaproliferin, beauvericin, enniatins, and moniliformin: a review. Crit Rev Food Sci Nutr. 2008 Jan;48(1):21-49. doi: 10.1080/10408390601062021. [18274964 ]
Gathercole PS, Thiel PG, Hofmeyr JH: Inhibition of pyruvate dehydrogenase complex by moniliformin. Biochem J. 1986 Feb 1;233(3):719-23. [3707519 ]

Target Details

5. Transketolase

General Function:: Transketolase activity
Specific Function:: Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.
Gene Name:: TKT
Uniprot ID:: P29401
Molecular Weight:: 67876.95 Da

References

Jestoi M: Emerging fusarium-mycotoxins fusaproliferin, beauvericin, enniatins, and moniliformin: a review. Crit Rev Food Sci Nutr. 2008 Jan;48(1):21-49. doi: 10.1080/10408390601062021. [18274964 ]
Burka LT, Doran J, Wilson BJ: Enzyme inhibition and the toxic action of moniliformin and other vinylogous alpha-ketoacids. Biochem Pharmacol. 1982 Jan 1;31(1):79-84. [7059356 ]

Target Details

6. Aldose reductase

General Function:: Glyceraldehyde oxidoreductase activity
Specific Function:: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Gene Name:: AKR1B1
Uniprot ID:: P15121
Molecular Weight:: 35853.125 Da

References

Jestoi M: Emerging fusarium-mycotoxins fusaproliferin, beauvericin, enniatins, and moniliformin: a review. Crit Rev Food Sci Nutr. 2008 Jan;48(1):21-49. doi: 10.1080/10408390601062021. [18274964 ]

7. 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

Celik M, Yilmaz S, Aksoy H, Unal F, Yuzbasioglu D, Donbak L: Evaluation of the genotoxicity of Fusarium mycotoxin moniliformin in human peripheral blood lymphocytes. Environ Mol Mutagen. 2009 Jun;50(5):431-4. doi: 10.1002/em.20459. [19230001 ]

Moniliformin (T3D3770)

Structure for T3D3770: Moniliformin

Targets

References

References

References

References

References

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References