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Record Information
Version3.6
Creation Date2006-05-22 15:12:04 UTC
Update Date2017-03-02 21:27:05 UTC
HMDB IDHMDB02704
Secondary Accession NumbersNone
Metabolite Identification
Common NameIduronic acid
DescriptionIduronic acid is a constituent of glycosaminoglycans heparin and heparan sulfate in varying proportions providing considerable diversity in sequence and biological function. The glycosaminoglycans (GAGs) are linear polysaccharides with alternating uronic acids (Iduronic acid and Glucuronic acid) and hexosamine residues, in which a limited set of monosaccharide units gives rise to a number of complex sequences by variable substitution with O-sulfate, N-sulfate, and N-acetyl groups. GAGs usually exist as the O-linked side-chains of proteoglycans, displaying a set of physiological functions which is remarkably wide and as yet incompletely explored. They may act as structural components of connective tissue and the extracellular matrix, or as specific ligands in the relationship between the cell surface and its surroundings. Heparan sulfate exists on the surface of most or all mammalian cells and can display a remarkable range of different sequence motifs; its range of interactions and possible functions reflect its structural complexity. The main repeat unit of heparin structurally resembles the protein binding sequences in heparan sulfate, but contains a higher percentage of sulfated residues. Utilized therapeutically as an anticoagulant and readily available in good quantities heparin serves as a useful model for heparan sulfate. Theoretical and experimental studies indicate that L-Iduronic acid residues of glycosaminoglycans are in equilibrium of different conformations, the relative proportion of conformers being a function of sulfation pattern and sequence. This unique conformational flexibility may provide an explanation for the stronger binding and associated higher biological activities of Iduronic acid-containing glycosaminoglycans (such as heparin, heparan sulfate and dermatan sulfate) as compared with other GAGs having similar charge density but with the more rigid glucuronic acid as the major uronic acid residue. Dermatan sulfates and heparins, which contain L-Iduronic acid in their backbone, show higher low-density lipoprotein (LDL)-affinity than chondroitin sulfates, which contain only D-glucuronic acid. Though confirming a non-specific, predominantly electrostatic interaction between GAGs and LDL, these results indicate modulation of LDL affinity by the polysaccharide backbone. Naturally oversulfated dermatan sulfate (SO3H/COOH ca. 1.2), mainly oversulfated at C-2 of Iduronic acid residues, show comparatively higher anticoagulant activity. (PMID: 3076283 , 8466951 , 8542607 , 11087707 ).
Structure
Thumb
Synonyms
ValueSource
IduronateHMDB
L-IduronateHMDB
L-Iduronic acidHMDB
Acid, iduronicMeSH
Chemical FormulaC6H10O7
Average Molecular Weight194.1394
Monoisotopic Molecular Weight194.042652674
IUPAC Name(2S,3R,4R,5S)-2,3,4,5-tetrahydroxy-6-oxohexanoic acid
Traditional Nameiduronic acid
CAS Registry Number3402-98-0
SMILES
O[C@H](C=O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O
InChI Identifier
InChI=1S/C6H10O7/c7-1-2(8)3(9)4(10)5(11)6(12)13/h1-5,8-11H,(H,12,13)/t2-,3+,4-,5+/m1/s1
InChI KeyIAJILQKETJEXLJ-LECHCGJUSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as glucuronic acid derivatives. These are compounds containing a glucuronic acid moiety (or a derivative), which consists of a glucose moiety with the C6 carbon oxidized to a carboxylic acid.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic oxygen compounds
Sub ClassOrganooxygen compounds
Direct ParentGlucuronic acid derivatives
Alternative Parents
Substituents
  • Glucuronic acid or derivatives
  • Hexose monosaccharide
  • Medium-chain hydroxy acid
  • Medium-chain fatty acid
  • Beta-hydroxy acid
  • Hydroxy fatty acid
  • Monosaccharide
  • Fatty acyl
  • Hydroxy acid
  • Fatty acid
  • Alpha-hydroxy acid
  • Beta-hydroxy aldehyde
  • Alpha-hydroxyaldehyde
  • Secondary alcohol
  • Polyol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Aldehyde
  • Carbonyl group
  • Alcohol
  • Organic oxide
  • Hydrocarbon derivative
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Lysosome
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility100.0 mg/mLALOGPS
logP-2.3ALOGPS
logP-3.2ChemAxon
logS-0.29ALOGPS
pKa (Strongest Acidic)3.24ChemAxon
pKa (Strongest Basic)-3.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area135.29 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity37.21 m3·mol-1ChemAxon
Polarizability16.1 Å3ChemAxon
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, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Lysosome
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Fibroblasts
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot Available
Normal
    details
    UrineDetected and Quantified0.017 - 0.15 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal
      • T. TOIDA, G. QIU,...
    details
    Abnormal Concentrations
    Not Available
    Associated Disorders and Diseases
    Disease ReferencesNone
    Associated OMIM IDsNone
    DrugBank IDNot Available
    DrugBank Metabolite IDNot Available
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB023047
    KNApSAcK IDNot Available
    Chemspider ID17794
    KEGG Compound IDC06472
    BioCyc IDCPD-12
    BiGG ID48353
    Wikipedia LinkIduronic acid
    NuGOwiki LinkHMDB02704
    Metagene LinkHMDB02704
    METLIN ID3331
    PubChem Compound18845
    PDB IDNot Available
    ChEBI ID24769
    References
    Synthesis ReferenceRoden, Lennart; Dorfman, Albert. Metabolism of mucopolysaccharides in mammalian tissues. V. Origin of L-iduronic acid. Journal of Biological Chemistry (1958), 233 1030-3.
    Material Safety Data Sheet (MSDS)Not Available
    General References
    1. Fuller M, Meikle PJ, Hopwood JJ: Glycosaminoglycan degradation fragments in mucopolysaccharidosis I. Glycobiology. 2004 May;14(5):443-50. Epub 2004 Jan 12. [PubMed:14718373 ]
    2. Cheng F, Petersson P, Arroyo-Yanguas Y, Westergren-Thorsson G: Differences in the uptake and nuclear localization of anti-proliferative heparan sulfate between human lung fibroblasts and human lung carcinoma cells. J Cell Biochem. 2001;83(4):597-606. [PubMed:11746503 ]
    3. Inoue H, Otsu K, Suzuki S, Nakanishi Y: Difference between N-acetylgalactosamine 4-sulfate 6-O-sulfotransferases from human serum and squid cartilage in specificity toward the terminal and interior portion of chondroitin sulfate. J Biol Chem. 1986 Apr 5;261(10):4470-5. [PubMed:3082866 ]
    4. Ginsberg LC, Di Ferrante DT, Di Ferrante N: A substrate for direct measurement of L-iduronic acid 2-sulfate sulfatase. Carbohydr Res. 1978 Jul;64:225-35. [PubMed:98232 ]
    5. Casu B, Petitou M, Provasoli M, Sinay P: Conformational flexibility: a new concept for explaining binding and biological properties of iduronic acid-containing glycosaminoglycans. Trends Biochem Sci. 1988 Jun;13(6):221-5. [PubMed:3076283 ]
    6. Gigli M, Ghiselli G, Torri G, Naggi A, Rizzo V: A comparative study of low-density lipoprotein interaction with glycosaminoglycans. Biochim Biophys Acta. 1993 Apr 7;1167(2):211-7. [PubMed:8466951 ]
    7. Bartolucci C, Cellai L, Iannelli MA, Lamba D, Liverani L, Mascellani G, Perola E: Inhibition of human leukocyte elastase by chemically and naturally oversulfated galactosaminoglycans. Carbohydr Res. 1995 Oct 23;276(2):401-8. [PubMed:8542607 ]
    8. Mulloy B, Forster MJ: Conformation and dynamics of heparin and heparan sulfate. Glycobiology. 2000 Nov;10(11):1147-56. [PubMed:11087707 ]

    Enzymes

    General function:
    Involved in sulfotransferase activity
    Specific function:
    Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan sulfate. Catalyzes the O-sulfation of glucosamine in IdoUA2S-GlcNS and also in IdoUA2S-GlcNH2. The substrate-specific O-sulfation generates an enzyme-modified heparan sulfate which acts as a binding receptor to Herpes simplex virus-1 (HSV-1) and permits its entry. Unlike 3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate.
    Gene Name:
    HS3ST3B1
    Uniprot ID:
    Q9Y662
    Molecular weight:
    43323.605
    General function:
    Involved in sulfotransferase activity
    Specific function:
    Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan sulfate. Catalyzes the O-sulfation of glucosamine in IdoUA2S-GlcNS and also in IdoUA2S-GlcNH2. The substrate-specific O-sulfation generates an enzyme-modified heparan sulfate which acts as a binding receptor to Herpes simplex virus-1 (HSV-1) and permits its entry. Unlike 3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate.
    Gene Name:
    HS3ST3A1
    Uniprot ID:
    Q9Y663
    Molecular weight:
    44899.155
    General function:
    Involved in sulfotransferase activity
    Specific function:
    Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan sulfate. Unlike 3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate (By similarity).
    Gene Name:
    HS3ST4
    Uniprot ID:
    Q9Y661
    Molecular weight:
    49798.645
    General function:
    Involved in sulfotransferase activity
    Specific function:
    Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan sulfate. Catalyzes the O-sulfation of glucosamine in GlcA2S-GlcNS. Unlike 3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate.
    Gene Name:
    HS3ST2
    Uniprot ID:
    Q9Y278
    Molecular weight:
    41500.57
    General function:
    Involved in transferase activity, transferring hexosyl groups
    Specific function:
    UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as estriol, 4-hydroxyestrone and 2-hydroxyestriol) and xenobiotics (such as 4-methylumbelliferone, 1-naphthol, 4-nitrophenol, 2-aminophenol, 4-hydroxybiphenyl and menthol). It is capable of 6 alpha-hydroxyglucuronidation of hyodeoxycholic acid.
    Gene Name:
    UGT2B4
    Uniprot ID:
    P06133
    Molecular weight:
    60512.035
    General function:
    Involved in transferase activity, transferring hexosyl groups
    Specific function:
    UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate.
    Gene Name:
    UGT1A4
    Uniprot ID:
    P22310
    Molecular weight:
    60024.535
    General function:
    Involved in transferase activity, transferring hexosyl groups
    Specific function:
    UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).
    Gene Name:
    UGT2B7
    Uniprot ID:
    P16662
    Molecular weight:
    60720.15
    General function:
    Involved in transferase activity, transferring hexosyl groups
    Specific function:
    UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.
    Gene Name:
    UGT1A1
    Uniprot ID:
    P22309
    Molecular weight:
    59590.91
    General function:
    Involved in transferase activity, transferring hexosyl groups
    Specific function:
    UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
    Gene Name:
    UGT1A9
    Uniprot ID:
    O60656
    Molecular weight:
    59940.495
    General function:
    Involved in transferase activity, transferring hexosyl groups
    Specific function:
    UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
    Gene Name:
    UGT1A6
    Uniprot ID:
    P19224
    Molecular weight:
    60750.215
    General function:
    Carbohydrate transport and metabolism
    Specific function:
    Not Available
    Gene Name:
    IDUA
    Uniprot ID:
    P35475
    Molecular weight:
    Not Available
    Reactions
    + Water → + Iduronic aciddetails
    + Water → + Iduronic aciddetails
    General function:
    Involved in sulfotransferase activity
    Specific function:
    Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of dermatan sulfate. Plays a pivotal role in the formation of 4-0-sulfated IdoA blocks in dermatan sulfate. Transfers sulfate to the C-4 hydroxyl of beta1,4-linked GalNAc that is substituted with an alpha-linked iduronic acid (IdoUA) at the C-3 hydroxyl. Transfers sulfate more efficiently to GalNAc residues in -IdoUA-GalNAc-IdoUA- than in -GlcUA-GalNAc-GlcUA-sequences. Has preference for partially desulfated dermatan sulfate. Addition of sulfate to GalNAc may occur immediately after epimerization of GlcUA to IdoUA. GlcUA to IdoUA. Appears to have an important role in the formation of the cerbellar neural network during postnatal brain development.
    Gene Name:
    CHST14
    Uniprot ID:
    Q8NCH0
    Molecular weight:
    42996.535
    General function:
    Involved in chondroitin-glucuronate 5-epimerase activity
    Specific function:
    Converts D-glucuronic acid to L-iduronic acid (IdoUA) residues.
    Gene Name:
    DSE
    Uniprot ID:
    Q9UL01
    Molecular weight:
    109772.235