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Record Information
Version3.6
Creation Date2006-05-22 14:17:34 UTC
Update Date2013-05-29 19:33:39 UTC
HMDB IDHMDB02061
Secondary Accession Numbers
  • HMDB06554
Metabolite Identification
Common NameHyaluronic acid
DescriptionHyaluronic acid (HA), is the most abundant glycosaminoglycan (GAG) in mammalian tissue. It is present in high concentrations in connective tissue, such as skin, vitreous humor, cartilage, and umbilical cord, but the largest single reservoir is the synovial fluid (SF) of the diarthrodial joints, where concentrations of 0.5-4 mg/mL are achieved. Hyaluronic acid, is the major hydrodynamic nonprotein component of joint SF. Its unique viscoelastic properties confer remarkable shock absorbing and lubricating abilities to SF, while its enormous macromolecular size and hydrophilicity serve to retain fluid in the joint cavity during articulation. HA restricts the entry of large plasma proteins and cells into SF but facilitates solute exchange between the synovial capillaries and cartilage and other joint tissues. In addition, HA can form a pericellular coat around cells, interact with proinflammatory mediators, and bind to cell receptors, such as cluster determinant (CD)44 and receptor for hyaluronate-mediated motility (RHAMM), where it modulates cell proliferation, migration, and gene expression. All these physicochemical and biologic properties of HA have been shown to be molecular weight (MW) dependent. The diverse physicochemical properties of HA arise from its unique macromolecular structure. The HA is an exceptionally long (3-30 μm) and unbranched nonsulfated GAG composed of repeating disaccharide units of N-acetylglucosamine, and glucuronic acid glycosidically linked through their respective 1-4 ring positions. Hydroxyl group oxygens at the glucuronyl-1 and glucosamine 3-positions are used for further polymerization of the HA disaccharide units to form chains that, when released from the cell plasma membrane, are of variable length and thus polydispersity. Despite the simplicity of the HA primary structure, this linear polyelectrolyte adopts complex conformations in solution, which engender it with diverse biologic properties. Within the joint cavity, HA molecules are predominately synthesized by the type B synovial cells. (PMID 12219318 ).
Structure
Thumb
Synonyms
  1. Hyaluronic acid
Chemical FormulaC16H27NO12
Average Molecular Weight425.3851
Monoisotopic Molecular Weight425.153325333
IUPAC Name(2S,3S,4R,5R)-6-{[(2R,3R,4R,5S,6R)-3-acetamido-5-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-4-yl]oxy}-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid
Traditional IUPAC Name(2S,3S,4R,5R)-6-{[(2R,3R,4R,5S,6R)-3-acetamido-5-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-4-yl]oxy}-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid
CAS Registry Number9004-61-9
SMILES
CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](OC2O[C@@H]([C@@H](OC)[C@H](O)[C@H]2O)C(O)=O)[C@H]1NC(C)=O
InChI Identifier
InChI=1S/C16H27NO12/c1-5(19)17-7-11(8(20)6(4-18)27-15(7)26-3)28-16-10(22)9(21)12(25-2)13(29-16)14(23)24/h6-13,15-16,18,20-22H,4H2,1-3H3,(H,17,19)(H,23,24)/t6-,7-,8-,9-,10-,11-,12+,13+,15-,16?/m1/s1
InChI KeyOEANUJAFZLQYOD-DDKBAWAXSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassCarbohydrates and Carbohydrate Conjugates
ClassDisaccharides
Sub ClassDihexoses
Other Descriptors
  • Aliphatic Heteropolycyclic Compounds
Substituents
  • 1,2 Diol
  • Acetal
  • Carboxamide Group
  • Carboxylic Acid
  • Dialkyl Ether
  • Glucosamine
  • Glucuronic Acid Or Derivative
  • Glucuronide
  • Glycosyl Compound
  • Mannosamine
  • O Glycosyl Compound
  • Oxane
  • Primary Alcohol
  • Secondary Alcohol
  • Secondary Carboxylic Acid Amide
  • Sugar Acid
Direct ParentDihexoses
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Extracellular
  • 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 solubility95.1 g/LALOGPS
logP-1.9ALOGPS
logP-3.4ChemAxon
logS-0.65ALOGPS
pKa (strongest acidic)3.19ChemAxon
pKa (strongest basic)-0.78ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count12ChemAxon
hydrogen donor count6ChemAxon
polar surface area193.47ChemAxon
rotatable bond count7ChemAxon
refractivity88.81ChemAxon
polarizability40.08ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Lysosome
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified0.24 (0.12-0.36) uMAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified1.2 (0.04-10.52) uMAdult (>18 years old)BothBiliary atresia details
BloodDetected and Quantified0.11 (0.044-0.74) uMNewborn (0-30 days old)BothHepatitis details
Cerebrospinal Fluid (CSF)Detected and Quantified0.25 (0.037-0.46) uMAdult (>18 years old)Not Specified
Epilepsy
details
Associated Disorders and Diseases
Disease References
Biliary atresia
  1. Ukarapol N, Wongsawasdi L, Ong-Chai S, Riddhiputra P, Kongtawelert P: Hyaluronic acid: additional biochemical marker in the diagnosis of biliary atresia. Pediatr Int. 2007 Oct;49(5):608-11. Pubmed: 17875085
Epilepsy
  1. Perosa SR, Porcionatto MA, Cukiert A, Martins JR, Amado D, Nader HB, Cavalheiro EA, Leite JP, Naffah-Mazzacoratti MG: Extracellular matrix components are altered in the hippocampus, cortex, and cerebrospinal fluid of patients with mesial temporal lobe epilepsy. Epilepsia. 2002;43 Suppl 5:159-61. Pubmed: 12121313
Hepatitis
  1. Ukarapol N, Wongsawasdi L, Ong-Chai S, Riddhiputra P, Kongtawelert P: Hyaluronic acid: additional biochemical marker in the diagnosis of biliary atresia. Pediatr Int. 2007 Oct;49(5):608-11. Pubmed: 17875085
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022824
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDC00518
BioCyc IDNot Available
BiGG ID35227
Wikipedia LinkHyaluronic acid
NuGOwiki LinkHMDB02061
Metagene LinkHMDB02061
METLIN IDNot Available
PubChem Compound53477741
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceTan, Wensong; Hu, Yihong; Zhang, Xu; Cai, Haibo. Method for preparing hyaluronic acid from microbial fermentation broth. Faming Zhuanli Shenqing Gongkai Shuomingshu (2007), 10pp.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Perosa SR, Porcionatto MA, Cukiert A, Martins JR, Amado D, Nader HB, Cavalheiro EA, Leite JP, Naffah-Mazzacoratti MG: Extracellular matrix components are altered in the hippocampus, cortex, and cerebrospinal fluid of patients with mesial temporal lobe epilepsy. Epilepsia. 2002;43 Suppl 5:159-61. Pubmed: 12121313
  2. Ghosh P, Guidolin D: Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: are the effects molecular weight dependent? Semin Arthritis Rheum. 2002 Aug;32(1):10-37. Pubmed: 12219318

Enzymes

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:
Involved in transferase activity, transferring hexosyl groups
Specific function:
Plays a role in hyaluronan/hyaluronic acid (HA) synthesis. Also able to catalyze the synthesis of chito-oligosaccharide depending on the substrate.
Gene Name:
HAS1
Uniprot ID:
Q92839
Molecular weight:
64831.425
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
Plays a role in hyaluronan/hyaluronic acid (HA) synthesis.
Gene Name:
HAS3
Uniprot ID:
O00219
Molecular weight:
62997.73
General function:
Involved in binding
Specific function:
Receptor for hyaluronic acid (HA). Mediates cell-cell and cell-matrix interactions through its affinity for HA, and possibly also through its affinity for other ligands such as osteopontin, collagens, and matrix metalloproteinases (MMPs). Adhesion with HA plays an important role in cell migration, tumor growth and progression. Also involved in lymphocyte activation, recirculation and homing, and in hematopoiesis. Altered expression or dysfunction causes numerous pathogenic phenotypes. Great protein heterogeneity due to numerous alternative splicing and post-translational modification events
Gene Name:
CD44
Uniprot ID:
P16070
Molecular weight:
81537.0
General function:
Cell wall/membrane/envelope biogenesis
Specific function:
Plays a role in hyaluronan/hyaluronic acid (HA) synthesis.
Gene Name:
HAS2
Uniprot ID:
Q92819
Molecular weight:
63565.845
General function:
Involved in binding
Specific function:
This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region
Gene Name:
ACAN
Uniprot ID:
P16112
Molecular weight:
250190.9
General function:
Involved in binding
Specific function:
Possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis
Gene Name:
TNFAIP6
Uniprot ID:
P98066
Molecular weight:
31203.1
General function:
Involved in sugar binding
Specific function:
May modulate neuronal adhesion and neurite growth during development by binding to neural cell adhesion molecules (NG-CAM and N-CAM). Chondroitin sulfate proteoglycan; binds to hyaluronic acid
Gene Name:
NCAN
Uniprot ID:
O14594
Molecular weight:
143092.1
General function:
Involved in sugar binding
Specific function:
May play a role in the terminally differentiating and the adult nervous system during postnatal development. Could stabilize interactions between hyaluronan (HA) and brain proteoglycans
Gene Name:
BCAN
Uniprot ID:
Q96GW7
Molecular weight:
99117.1
General function:
Involved in binding
Specific function:
May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid
Gene Name:
VCAN
Uniprot ID:
P13611
Molecular weight:
372816.9
General function:
Replication, recombination and repair
Specific function:
Involved in cell motility. When hyaluronan binds to HMMR, the phosphorylation of a number of proteins, including the focal adhesion kinase occurs. May also be involved in cellular transformation and metastasis formation, and in regulating extracellular-regulated kinase (ERK) activity
Gene Name:
HMMR
Uniprot ID:
O75330
Molecular weight:
84099.8
General function:
Involved in binding
Specific function:
Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Acts also, in different species, as a primary systemic scavenger receptor for heparin (Hep), chondroitin sulfate (CS), dermatan sulfate (DS), nonglycosaminoglycan (GAG), acetylated low-density lipoprotein (AcLDL), pro-collagen propeptides and advanced glycation end products (AGE). May serve to maintain tissue integrity by supporting extracellular matrix turnover or it may contribute to maintaining fluidity of bodily liquids by resorption of hyaluronan. Counter receptor which plays an important role in lymphocyte recruitment in the hepatic vasculature. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. The proteolytically processed 190 kDa form also functions as an endocytosis receptor for heparin internalisation as well as HA and CS
Gene Name:
STAB2
Uniprot ID:
Q8WWQ8
Molecular weight:
276985.6
General function:
Involved in binding
Specific function:
Ligand-specific transporter trafficking between intracellular organelles (TGN) and the plasma membrane. Plays a role in autocrine regulation of cell growth mediated by growth regulators containing cell surface retention sequence binding (CRS). May act as an hyaluronan (HA) transporter, either mediating its uptake for catabolism within lymphatic endothelial cells themselves, or its transport into the lumen of afferent lymphatic vessels for subsequent re-uptake and degradation in lymph nodes
Gene Name:
LYVE1
Uniprot ID:
Q9Y5Y7
Molecular weight:
35213.1
General function:
Involved in binding
Specific function:
Stabilizes the aggregates of proteoglycan monomers with hyaluronic acid in the extracellular cartilage matrix
Gene Name:
HAPLN1
Uniprot ID:
P10915
Molecular weight:
40165.2
General function:
Involved in binding
Specific function:
Mediates a firm binding of versican V2 to hyaluronic acid. May play a pivotal role in the formation of the hyaluronan- associated matrix in the central nervous system (CNS) which facilitates neuronal conduction and general structural stabilization. Binds to hyaluronic acid
Gene Name:
HAPLN2
Uniprot ID:
Q9GZV7
Molecular weight:
37774.7
General function:
Involved in binding
Specific function:
May function in hyaluronic acid binding
Gene Name:
HAPLN3
Uniprot ID:
Q96S86
Molecular weight:
40894.0
General function:
Involved in binding
Specific function:
Binds to hyaluronic acid and may be involved in formation of the extracellular matrix
Gene Name:
HAPLN4
Uniprot ID:
Q86UW8
Molecular weight:
42801.1
General function:
Involved in binding
Specific function:
Acts as a scavenger receptor for acetylated low density lipoprotein. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. When inhibited in endothelial tube formation assays, there is a marked decrease in cell-cell interactions, suggesting a role in angiogenesis. Involved in the delivery of newly synthesized CHID1/SI-CLP from the biosynthetic compartment to the endosomal/lysosomal system
Gene Name:
STAB1
Uniprot ID:
Q9NY15
Molecular weight:
275479.9
General function:
Involved in binding
Specific function:
Receptor for hyaluronate
Gene Name:
LAYN
Uniprot ID:
Q6UX15
Molecular weight:
43108.1
General function:
Involved in binding
Specific function:
Not Available
Gene Name:
SUSD5
Uniprot ID:
O60279
Molecular weight:
68020.6