| Hyaluronidase |
|
| Identifiers |
| EC number |
3.2.1.35 |
| CAS number |
37326-33-3 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
|
| Hyaluronidase |
| Identifiers |
| Symbol |
Hyaluronidase_1 |
| Pfam |
PF07212 |
| InterPro |
IPR009860 |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe; PDBj |
| PDBsum |
structure summary |
|
| Hyaluronidase |
| Identifiers |
| Symbol |
Hyaluronidase_2 |
| Pfam |
PF07555 |
| InterPro |
IPR011496 |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe; PDBj |
| PDBsum |
structure summary |
|
The hyaluronidases (EC 3.2.1.35) are a family of enzymes that degrade hyaluronic acid. Karl Meyer [1] classified these enzymes in 1971 into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyaluronidases are two classes of eukaryotic endoglycosidase hydrolases and a prokaryotic lyase-type of glycosidase.
In humans, there are six associated genes, including HYAL1, HYAL2, HYAL3, and PH-20/SPAM1.[2]
Contents
- 1 Use as a drug
- 2 Role in cancer
- 3 Role in pathogenesis
- 4 Role in fertilization
- 5 References
- 6 External links
Use as a drug
Hyaluronidase
| Systematic (IUPAC) name |
|
hyaluronidase
|
| Clinical data |
| AHFS/Drugs.com |
Consumer Drug Information |
Pregnancy
category |
|
Routes of
administration |
subcutaneous |
| Identifiers |
| CAS Number |
488712-31-8 Y |
| ATC code |
B06AA03 |
| DrugBank |
DB00070 Y |
| ChemSpider |
none |
| UNII |
8KOG53Z5EM Y |
| ChEMBL |
CHEMBL1201636 N |
| Chemical data |
| Formula |
C2455H3775N617O704S21 |
| Molar mass |
53870.9 g/mol |
| NY (what is this?) (verify) |
By catalyzing the hydrolysis of hyaluronan, a constituent of the extracellular matrix (ECM), hyaluronidase lowers the viscosity of hyaluronan, thereby increasing tissue permeability. It is, therefore, used in medicine in conjunction with other drugs to speed their dispersion and delivery. Common applications are ophthalmic surgery, in combination with local anesthetics. It also increases the absorption rate of parenteral fluids given by hypodermoclysis, and is an adjunct in subcutaneous urography for improving resorption of radiopaque agents. Hyaluronidase is also used for extravasation of hyperosmolar solutions.
Brand names of animal-derived hyaluronidase include HydaseTM (developed and manufactured by PrimaPharm Inc., distributed by Akorn Inc.), which has been FDA-approved as a "thimerosal-free" animal-derived hyaluronidase, Vitrase (Bausch + Lomb/Valeant Pharmaceuticals), Amphadase (Amphastar Pharmaceuticals), and Wydase. Wydase, however, is no longer manufactured.
On December 2, 2005, the FDA approved a synthetic (recombinant or rDNA) "human" hyaluronidase, Hylenex (Halozyme Therapeutics).[3] The FDA also approved HyQvia in late 2014,[4] a form of sub-cutaneous immunoglobulin (SCIG) that uses Hylenex to allow for a far greater volume of SCIG to be administered than would normally be possible to administer sub-cutaneously, providing a form of SCIG that can be dosed on a monthly basis, a longer period of time than other forms of SCIG allow. HyQvia had a rate of systemic adverse effects higher than traditional subcutaneous forms of immunoglobulin injection, but lower than those typical in IVIG patients.[5]
Role in cancer
The role of hyaluronidases in cancer is controversial, however there is substantial evidence of increased hyaluronidase activity in malignancies.[6][7] Limited data support a role of lysosomal hyaluronidases in metastasis, while other data support a role in tumor suppression. Other studies suggest no contribution or effects independent of enzyme activity. Non-specific inhibitors (apigenin, sulfated glycosaminoglycans) or crude enzyme extracts have been used to test most hypotheses, making data difficult to interpret. It has been hypothesized that, by helping degrade the ECM surrounding the tumor, hyaluronidases help cancer cells escape from primary tumor masses. However, studies show that removal of hyaluronan from tumors prevents tumor invasion. Hyaluronidases are also thought to play a role in the process of angiogenesis, although most hyaluronidase preparations are contaminated with large amounts of angiogeneic growth factors.[8] As previously mentioned, there are six hyaluronidase genes in the human genome, three of which can express active hyaluronidases (HYAL1, HYAL2 and PH20).
Role in pathogenesis
Some bacteria, such as Staphylococcus aureus, Streptococcus pyogenes,[9] and Clostridium perfringens,[10] produce hyaluronidase as a means of using hyaluronan as a carbon source. It is often speculated that Streptococcus and Staphylococcus pathogens use hyaluronidase as a virulence factor to destroy the polysaccharide that holds animal cells together, making it easier for the pathogen to spread through the tissues of the host organism, but no valid experimental data are available to support this hypothesis.
Role in fertilization
In most mammalian fertilization, hyaluronidase is released by the acrosome of the sperm cell after it has reached the oocyte, by digesting hyaluronan in the corona radiata, thus enabling conception. Gene-targeting studies show that hyaluronidases such as PH20 are not essential for fertilization, although exogenous hyaluronidases can disrupt the cumulus matrix.
The majority of mammalian ova are covered in a layer of granulosa cells intertwined in an ECM that contains a high concentration of hyaluronan. When a capacitated sperm reaches the ovum, it is able to penetrate this layer with the assistance of hyaluronidase enzymes present on the surface of the sperm. Once this occurs, the sperm is capable of binding with the zona pellucida, and the acrosome reaction can occur.[11]
References
- ^ Meyer, K (1971). "Hyaluronidases". In Boyer PD. Enzymes V. New York: Academic Press. pp. 307–320. ISBN 978-0-12-122705-0.
- ^ Csoka AB, Frost GI, Stern R (December 2001). "The six hyaluronidase-like genes in the human and mouse genomes". Matrix biology : journal of the International Society for Matrix Biology 20 (8): 499–508. doi:10.1016/S0945-053X(01)00172-X. PMID 11731267.
- ^ "Halozyme Therapeutics and Baxter Healthcare Corporation Announce FDA Approval of Hylenex". Archived from the original on October 18, 2007. Retrieved 2008-11-07.
- ^ "September 12, 2004 Approval Letter". FDA. FDA.gov. Retrieved 20 November 2015.
- ^ Sanford, Mark (13 June 2014). "Human Immunoglobulin 10 % with Recombinant Human Hyaluronidase: Replacement Therapy in Patients with Primary Immunodeficiency Disorders". BioDrugs 28 (4): 411–420. doi:10.1007/s40259-014-0104-3.
- ^ Involvement of hyaluronidases in colorectal cancer.BMC Cancer. 2010
- ^ Elevated tissue expression of hyaluronic acid and hyaluronidase validates the HA-HAase urine test for bladder cancer. J Urol. 2001.[1]
- ^ <Int J Cancer. 2002 Feb 10;97(5):601-7>[2]
- ^ Starr CR, Engleberg NC (January 2006). "Role of hyaluronidase in subcutaneous spread and growth of group A streptococcus". Infection and immunity 74 (1): 40–8. doi:10.1128/IAI.74.1.40-48.2006. PMC 1346594. PMID 16368955.
- ^ Zukaite V, Biziulevicius GA (March 2000). "Acceleration of hyaluronidase production in the course of batch cultivation of Clostridium perfringens can be achieved with bacteriolytic enzymes". Letters in applied microbiology 30 (3): 203–6. doi:10.1046/j.1472-765x.2000.00693.x. PMID 10747251.
- ^ Alberts, Bruce (2008). Molecular biology of the cell. New York: Garland Science. p. 1298. ISBN 0-8153-4105-9.
External links
- Hyaluronidase at the US National Library of Medicine Medical Subject Headings (MeSH)
|
Hydrolase: sugar hydrolases (EC 3.2)
|
|
| 3.2.1: Glycoside hydrolases |
| Disaccharidase |
- Sucrase/Sucrase-isomaltase/Invertase
- Maltase
- Trehalase
- Lactase
|
|
| Glucosidases |
- Cellulase
- Alpha-glucosidase
- Acid
- Neutral AB
- Neutral C
- Beta-glucosidase
- Debranching enzyme
|
|
| Other |
- Amylase
- Chitinase
- Lysozyme
- Neuraminidase
- NEU1
- NEU2
- NEU3
- NEU4
- Bacterial neuraminidase
- Viral neuraminidase
- Galactosidases
- alpha-Mannosidase
- Glucuronidase
- Hyaluronidase
- Pullulanase
- Glucosylceramidase
- Galactosylceramidase
- Alpha-N-acetylgalactosaminidase
- Alpha-N-acetylglucosaminidase
- Fucosidase
- Hexosaminidase
- Iduronidase
- Maltase-glucoamylase
- Heparanase
|
|
|
3.2.2: Hydrolysing
N-Glycosyl compounds |
- DNA glycosylases: Oxoguanine glycosylase
|
|
- Biochemistry overview
- Enzymes overview
- By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15-99
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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Proteins: enzymes
|
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| Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
- Enzyme kinetics
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
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| Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
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| Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
|
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| Types |
- EC1 Oxidoreductases(list)
- EC2 Transferases(list)
- EC3 Hydrolases(list)
- EC4 Lyases(list)
- EC5 Isomerases(list)
- EC6 Ligases(list)
|
|
- Biochemistry overview
- Enzymes overview
- By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15-99
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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