Tmic
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Record Information
Version2.0
Creation Date2010-05-06 16:13:07 UTC
Update Date2014-12-24 20:26:28 UTC
Accession NumberT3D3738
Identification
Common NamePenicillic acid
ClassSmall Molecule
DescriptionPenicillic acid is a mycotoxin produced by several species of Aspergillus and Penicillium. It has antibiotic activity and is cytotoxic, hepatotoxic, and carcinogenic. Penicillic acid is a human health hazard because it can be found on contaminated crops such as corn. (1, 8)
Compound Type
  • Ether
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
3-Methoxy-5-methyl-4-oxo-2,5-hexadienoic acid
3-Methoxy-5-methyl-4-oxohexa-2,5-dienoic acid
Kyselina penicilova
PA
Pencillic acid
Penicillate
Chemical FormulaC8H10O4
Average Molecular Mass170.163 g/mol
Monoisotopic Mass170.058 g/mol
CAS Registry Number90-65-3
IUPAC Name3-methoxy-5-methyl-4-oxohexa-2,5-dienoic acid
Traditional Namepenicillic acid
SMILESCOC(=CC(O)=O)C(=O)C(C)=C
InChI IdentifierInChI=1S/C8H10O4/c1-5(2)8(11)6(12-3)4-7(9)10/h4H,1H2,2-3H3,(H,9,10)/b6-4-
InChI KeyInChIKey=VOUGEZYPVGAPBB-XQRVVYSFSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as medium-chain keto acids and derivatives. These are keto acids with a 6 to 12 carbon atoms long side chain.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassKeto acids and derivatives
Sub ClassMedium-chain keto acids and derivatives
Direct ParentMedium-chain keto acids and derivatives
Alternative Parents
Substituents
  • Medium-chain keto acid
  • Branched fatty acid
  • Fatty acyl
  • Alpha-branched alpha,beta-unsaturated-ketone
  • Unsaturated fatty acid
  • Acryloyl-group
  • Enone
  • Vinylogous ester
  • Alpha,beta-unsaturated ketone
  • Ketone
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Organic oxygen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organic oxide
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
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 Point83°C-87°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility5.1 g/LALOGPS
logP1.15ALOGPS
logP1.03ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)3.2ChemAxon
pKa (Strongest Basic)-5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity43.88 m³·mol⁻¹ChemAxon
Polarizability16.21 ųChemAxon
Number of Rings0ChemAxon
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, Positivesplash10-0udi-1900000000-95a2b38d3586a4e6d3efView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udl-7900000000-f7f77d2e681a97920f49View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014l-9000000000-073d0101d9c7b78f0bd4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0900000000-e46f254c05a55f48a00dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0gdi-1900000000-6c6b1481406112626108View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0gbd-9200000000-f61dcbb3e46683ed987fView in MoNA
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (10)
Mechanism of ToxicityPenicillic acid has been shown to inhibit alcohol and lactate dehydrogenases by forming covalent adducts with either cysteine or lysine residues at the enzyme active sites. Penicillic acid also binds directly to the active center cysteine in the large subunit of caspase-8, thus inhibiting FasL-induced apoptosis by targeting self-processing of caspase-8. Penicillic acid is also mutagenic and can cause DNA single-strand breaks, chromosome aberrations, and inhibition of DNA synthesis. Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity. (1, 2, 3, 5, 7, 9)
MetabolismPenicillic acid is rapidly absorbed and extensively metabolized in the liver. Detoxification occurs via interactions with glutathione S-transferases and metabolites are excreted mainly in the urine. (6, 8)
Toxicity ValuesLD50: 600 mg/kg (Oral, Mouse) (8) LD50: 250 mg/kg (Intravenous, Mouse) (8) LD50: 90 mg/kg (Intraperitoneal, Mouse) (8)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (11)
Uses/SourcesPenicillic acid is a mycotoxin produced by several species of Aspergillus and Penicillium. It is a human health hazard because it can be found on contaminated crops such as corn. (8)
Minimum Risk LevelNot Available
Health EffectsPenicillic acid is cytotoxic, hepatotoxic, and carcinogenic. (8)
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID5385314
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 LinkPenicillic_acid
References
Synthesis ReferenceNot Available
MSDST3D3738.pdf
General References
  1. Ashoor SH, Chu FS: Inhibition of alcohol and lactic dehydrogenases by patulin and penicillic acid in vitro. Food Cosmet Toxicol. 1973 Aug;11(4):617-24. [4586181 ]
  2. Kimmel JL, Tipton PA: Inactivation of GDP-mannose dehydrogenase from Pseudomonas aeruginosa by penicillic acid identifies a critical active site loop. Arch Biochem Biophys. 2005 Sep 15;441(2):132-40. [16111644 ]
  3. Bando M, Hasegawa M, Tsuboi Y, Miyake Y, Shiina M, Ito M, Handa H, Nagai K, Kataoka T: The mycotoxin penicillic acid inhibits Fas ligand-induced apoptosis by blocking self-processing of caspase-8 in death-inducing signaling complex. J Biol Chem. 2003 Feb 21;278(8):5786-93. Epub 2002 Dec 12. [12482880 ]
  4. Grabsch C, Wichmann G, Loffhagen N, Herbarth O, Muller A: Cytotoxicity assessment of gliotoxin and penicillic acid in Tetrahymena pyriformis. Environ Toxicol. 2006 Apr;21(2):111-7. [16528685 ]
  5. Stetina R: Induction of DNA single-strand breaks and DNA synthesis inhibition in CHO and AWRF cells after exposure to sterigmatocystin and penicillic acid. Folia Biol (Praha). 1986;32(6):406-13. [3100345 ]
  6. Dierickx PJ, De Beer JO: Interaction of the mycotoxin penicillic acid with glutathione and rat liver glutathione S-transferases. Mycopathologia. 1984 Jun 30;86(3):137-41. [6472435 ]
  7. Umeda M, Tsutsui T, Saito M: Mutagenicity and inducibility of DNA single-strand breaks and chromosome aberrations by various mycotoxins. Gann. 1977 Oct;68(5):619-25. [563356 ]
  8. Chan PK, Hayes AW, Siraj MY, Meydrech EF: Pharmacokinetics of the mycotoxin penicillic acid in male mice: absorption, distribution, excretion, and kinetics. Toxicol Appl Pharmacol. 1984 Apr;73(2):195-203. [6710521 ]
  9. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
  10. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  11. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Ubiquitin protein ligase binding
Specific Function:
Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.
Gene Name:
CASP8
Uniprot ID:
Q14790
Molecular Weight:
55390.53 Da
References
  1. Bando M, Hasegawa M, Tsuboi Y, Miyake Y, Shiina M, Ito M, Handa H, Nagai K, Kataoka T: The mycotoxin penicillic acid inhibits Fas ligand-induced apoptosis by blocking self-processing of caspase-8 in death-inducing signaling complex. J Biol Chem. 2003 Feb 21;278(8):5786-93. Epub 2002 Dec 12. [12482880 ]
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. Stetina R: Induction of DNA single-strand breaks and DNA synthesis inhibition in CHO and AWRF cells after exposure to sterigmatocystin and penicillic acid. Folia Biol (Praha). 1986;32(6):406-13. [3100345 ]
  2. Umeda M, Tsutsui T, Saito M: Mutagenicity and inducibility of DNA single-strand breaks and chromosome aberrations by various mycotoxins. Gann. 1977 Oct;68(5):619-25. [563356 ]
General Function:
Nad binding
Specific Function:
Not Available
Gene Name:
LDHA
Uniprot ID:
P00338
Molecular Weight:
36688.465 Da
References
  1. Ashoor SH, Chu FS: Inhibition of alcohol and lactic dehydrogenases by patulin and penicillic acid in vitro. Food Cosmet Toxicol. 1973 Aug;11(4):617-24. [4586181 ]
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name:
SLC22A11
Uniprot ID:
Q9NSA0
Molecular Weight:
59970.945 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular Weight:
60025.025 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]