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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-05-22 14:17:49 UTC
Update Date2019-03-29 18:21:04 UTC
HMDB IDHMDB0002349
Secondary Accession Numbers
  • HMDB02349
Metabolite Identification
Common Nametrans-trans-Muconic acid
Descriptiontrans,trans-Muconic acid is a urinary metabolite of benzene and has been used as a biomarker of exposure to benzene in humans exposed to levels as low as 1 ppm. However, muconic acid is known that may also be derived from sorbic acid and its salts. Dietary supplementation with 500 mg sorbic acid significantly increases the urinary trans,trans-Muconic acid excretion. Under study conditions 0.12% of the sorbic acid dose is excreted in urine as trans, trans muconic acid thereby indicating that a typical dietary intake of 6 - 30 mg/day of sorbic acid accounts for 10 -50% of the background of trans, trans muconic acid excretion in nonsmokers, and for 5 - 25% in smokers. (PMID 8021961 , 1487326 , 9137998 , Int Arch Occup Environ Health. 1997;69(4):247-51.). trans,trans-Muconic acid has been found to be a metabolite in Escherichia coli and Pseudomonas putida (PMID: 26360870 ).
Structure
Data?1547234219
Synonyms
ValueSource
(2Z,4Z)-HEXA-2,4-dienedioIC ACIDChEBI
(Z,Z)-2,4-Hexadienedioic acidChEBI
cis,cis-2,4-Hexadienedioic acidChEBI
cis,cis-HexadienedioateKegg
(2Z,4Z)-HEXA-2,4-dienedioateGenerator
(Z,Z)-2,4-HexadienedioateGenerator
cis,cis-2,4-HexadienedioateGenerator
cis,cis-Hexadienedioic acidGenerator
trans-trans-MuconateGenerator
cis,cis-MuconateHMDB
2,4-HexadienedioateHMDB
2,4-Hexadienedioic acidHMDB
Muconic acidHMDB
Muconic acid, (e,e)-isomerHMDB
trans-beta-Hydromuconic acidHMDB
trans,trans-Muconic acidHMDB
Chemical FormulaC6H6O4
Average Molecular Weight142.1094
Monoisotopic Molecular Weight142.02660868
IUPAC Name(2Z,4Z)-hexa-2,4-dienedioic acid
Traditional Namemuconic acid
CAS Registry Number3588-17-8
SMILES
OC(=O)\C=C\C=C\C(O)=O
InChI Identifier
InChI=1S/C6H6O4/c7-5(8)3-1-2-4-6(9)10/h1-4H,(H,7,8)(H,9,10)/b3-1+,4-2+
InChI KeyTXXHDPDFNKHHGW-ZPUQHVIOSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as medium-chain fatty acids. These are fatty acids with an aliphatic tail that contains between 4 and 12 carbon atoms.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentMedium-chain fatty acids
Alternative Parents
Substituents
  • Medium-chain fatty acid
  • Unsaturated fatty acid
  • Dicarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point301 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.2 mg/mL at 15 °CNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility3.48 g/LALOGPS
logP0.67ALOGPS
logP0.49ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)3.87ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity34.93 m³·mol⁻¹ChemAxon
Polarizability12.58 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-00di-3950000000-4833ed03fecc5d107087JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00di-3950000000-4833ed03fecc5d107087JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-0920000000-25984cbefee561769fe3JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0005-9400000000-1d771b996d6b60d97202JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00dj-8930000000-43cca1649a383c178957JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-0a4i-9500000000-9bfca1b46934aca91417JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-0a4i-9100000000-f73acaf474e29ae6ad02JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-0a4i-9100000000-f2b4bdcda5ec550eb792JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-0006-2900000000-1ba3b45cf195a5a99f0cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-0a4i-9000000000-dfbcd30eacb1562a4b6eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0a4i-9000000000-55d282ca59f262ec6571JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0a4i-9000000000-6d6fa71ac1d98156ceb5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0a4i-9000000000-b0b000b29f1354ee4c06JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0006-2900000000-1ba3b45cf195a5a99f0cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-dfbcd30eacb1562a4b6eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-55d282ca59f262ec6571JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-6d6fa71ac1d98156ceb5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-b0b000b29f1354ee4c06JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-1900000000-af70de4037dff7de9451JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004j-9700000000-9bf9b99450c76793d87bJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ug0-9000000000-227dbb1efce65ff24c43JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-1900000000-70540641b312f5201a47JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-006x-3900000000-2f635f40772c5e68fd4dJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0fi4-9400000000-803dce4e7fbd2d6c9ac7JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Feces
  • Urine
Tissue Locations
  • Platelet
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot Available
Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified0.03 +/- 0.016 umol/mmol creatinineAdult (>18 years old)MaleNormal details
    Abnormal Concentrations
    BiospecimenStatusValueAgeSexConditionReferenceDetails
    UrineDetected and Quantified0.1 (0.05 - 0.3) umol/mmol creatinineAdult (>18 years old)BothSmoking details
    UrineDetected and Quantified0.16 +/- 0.02 umol/mmol creatinineAdult (>18 years old)Male
    Benzene exposure
    details
    Associated Disorders and Diseases
    Disease References
    Benzene exposure
    1. Chanvaivit S, Navasumrit P, Hunsonti P, Autrup H, Ruchirawat M: Exposure assessment of benzene in Thai workers, DNA-repair capacity and influence of genetic polymorphisms. Mutat Res. 2007 Jan 10;626(1-2):79-87. Epub 2006 Nov 13. [PubMed:17095285 ]
    Smoking
    1. Ruppert T, Scherer G, Tricker AR, Adlkofer F: trans,trans-muconic acid as a biomarker of non-occupational environmental exposure to benzene. Int Arch Occup Environ Health. 1997;69(4):247-51. [PubMed:9137998 ]
    Associated OMIM IDsNone
    DrugBank IDNot Available
    Phenol Explorer Compound IDNot Available
    FoodDB IDFDB023893
    KNApSAcK IDC00007490
    Chemspider ID4444151
    KEGG Compound IDC02480
    BioCyc IDNot Available
    BiGG ID36677
    Wikipedia LinkNot Available
    METLIN IDNot Available
    PubChem Compound5280518
    PDB IDNot Available
    ChEBI ID16508
    References
    Synthesis ReferenceErlenmeyer, H.; Schoenauer, W. A synthesis of trans-trans-muconic acid from fumaric acid. Helvetica Chimica Acta (1937), 20 1008-12.
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. Renner T, Baer-Koetzle M, Scherer G: Determination of sorbic acid in urine by gas chromatography-mass spectrometry. J Chromatogr A. 1999 Jun 25;847(1-2):127-33. [PubMed:10431356 ]
    2. Kim S, Vermeulen R, Waidyanatha S, Johnson BA, Lan Q, Rothman N, Smith MT, Zhang L, Li G, Shen M, Yin S, Rappaport SM: Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism. Carcinogenesis. 2006 Apr;27(4):772-81. Epub 2005 Dec 8. [PubMed:16339183 ]
    3. Wiwanitkit V, Suwansaksri J, Soogarun S: The urine trans, trans muconic acid biomarker and platelet count in a sample of subjects with benzene exposure. Clin Appl Thromb Hemost. 2004 Jan;10(1):73-6. [PubMed:14979410 ]
    4. Hecht SS: Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer. Carcinogenesis. 2002 Jun;23(6):907-22. [PubMed:12082012 ]
    5. Ruppert T, Scherer G, Tricker AR, Adlkofer F: trans,trans-muconic acid as a biomarker of non-occupational environmental exposure to benzene. Int Arch Occup Environ Health. 1997;69(4):247-51. [PubMed:9137998 ]
    6. Bartczak A, Kline SA, Yu R, Weisel CP, Goldstein BD, Witz G, Bechtold WE: Evaluation of assays for the identification and quantitation of muconic acid, a benzene metabolite in human urine. J Toxicol Environ Health. 1994 Jul;42(3):245-58. [PubMed:8021961 ]
    7. Ducos P, Gaudin R, Bel J, Maire C, Francin JM, Robert A, Wild P: trans,trans-Muconic acid, a reliable biological indicator for the detection of individual benzene exposure down to the ppm level. Int Arch Occup Environ Health. 1992;64(5):309-13. [PubMed:1487326 ]
    8. Becker J, Lange A, Fabarius J, Wittmann C: Top value platform chemicals: bio-based production of organic acids. Curr Opin Biotechnol. 2015 Dec;36:168-75. doi: 10.1016/j.copbio.2015.08.022. Epub 2015 Sep 8. [PubMed:26360870 ]