Hyaluronidase
Hyaluronidase | |||||||||
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ExPASy NiceZyme view | | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Hyaluronidase | |||||||||
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Identifiers | |||||||||
Symbol | Hyaluronidase_1 | ||||||||
Pfam | PF07212 | ||||||||
InterPro | IPR009860 | ||||||||
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Hyaluronidase | |||||||||
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Identifiers | |||||||||
Symbol | Hyaluronidase_2 | ||||||||
Pfam | PF07555 | ||||||||
InterPro | IPR011496 | ||||||||
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Hyaluronidases are a family of
In humans, there are five functional hyaluronidases:
Hyaluronidases are hyaluronoglucosidases (EC 3.2.1.35), i.e. they cleave the (1→4)-linkages between N-acetylglucosamine and glucuronate. The term hyaluronidase may also refer to hyaluronoglucuronidases (EC 3.2.1.36), which cleave (1→3)-linkages. In addition, bacterial hyaluronate lyases (EC 4.2.2.1) may also be referred to as hyaluronidases, although this is uncommon.[6]
Use as a drug
Clinical data | |
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Pronunciation | /haɪ(ə)ljuˌrɑːnɪˈdeɪs/[7] |
Trade names | Hylenex, HyQvia, Vitrase, others |
Other names | hyaluronidase-fihj, hyaluronidase-oysk, hyaluronidase-zzxf |
AHFS/Drugs.com | Micromedex Detailed Consumer Information |
License data | |
Pregnancy category |
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Subcutaneous | |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
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CAS Number | |
DrugBank | |
ChemSpider |
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UNII | |
KEGG | |
ChEMBL | |
Chemical and physical data | |
Formula | C2455H3775N617O704S21 |
Molar mass | 53871.08 g·mol−1 |
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Medical uses
By
Purified and recombinant hyaluronidases
Four different purified hyaluronidases have been approved for use in the United States, three of animal origin and one recombinant. They are indicated as adjuvants in subcutaneous fluid administration for achieving hydration, for increasing the dispersion and absorption of other injected drugs, or for improving resorption of radiopaque agents, in subcutaneous urography.[14][15][16]
The three naturally-sourced hyaluronidases are orthologs of human HYAL5 (PH20) obtained from testicular preparations. They are sold under the trade names Vitrase (ovine, FDA-approved in May 2004),[17] Amphadase (bovine, October 2004)[18] and Hydase (bovine, October 2005).[19]
Human recombinant hyaluronidase (Hylenex)—approved for use in the United States in December 2005[20][21]—corresponds to the soluble fragment of human HYAL5 (PH20) produced in culture by genetically engineered Chinese hamster ovary cells containing a DNA plasmid encoding the enzyme.[22]
Combination treatments
A human recombinant hyaluronidase kit, HyQvia, was approved for use in the European Union in May 2013,[23] and in the United States in September 2014.[24][25] It is a dual vial unit with one vial of immune globulin infusion 10% (human) and one vial of recombinant human hyaluronidase.[26] It is an immune globulin with a recombinant human hyaluronidase indicated in the United States for the treatment of primary immunodeficiency in adults. This includes, but is not limited to, common variable immunodeficiency, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.[26] In the European Union it is indicated as replacement therapy in adults, children and adolescents (0–18 years) in:
- Primary immunodeficiency syndromes with impaired antibody production.[23]
- Hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic leukaemia, in whom prophylactic antibiotics have failed or are contra‑indicated.[23]
- Hypogammaglobulinaemia and recurrent bacterial infections in multiple myeloma (MM) patients.[23]
- Hypogammaglobulinaemia in patients pre‑ and post‑allogeneic hematopoietic stem cell transplantation.[23]
A form of
]Hyaluronidase is available in some
In July 2021, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj in combination with pomalidomide and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor.[35]
Efgartigimod alfa/hyaluronidase (Vyvgart Hytrulo) was approved for the treatment of generalized myasthenia gravis in the United States in June 2023.[36][37]
Role in cancer
The role of hyaluronidases in cancer has been historically controversial due to contradictory observations,
Elevated tissue expression of hyaluronic acid and hyaluronidase validates the hyaluronic acid-hyaluronidases urine test for bladder cancer.[41] 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 extracellular matrix surrounding the tumor, hyaluronidases help cancer cells escape from primary tumor masses. However, studies show that removal of hyaluronan from tumors prevents tumor invasion.[citation needed] Hyaluronidases are also thought to play a role in the process of angiogenesis, although most hyaluronidase preparations are contaminated with large amounts of angiogenic growth factors.[42]
Role in pathogenesis
Some bacteria, such as Staphylococcus aureus, Streptococcus pyogenes,[43] and Clostridium perfringens,[44] 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.[citation needed]
Hyaluronidases are found in the venom of certain lizards and snakes, as well as honeybees, where they are referred to as "spreading factors", having a function akin to bacterial hyaluronidases.[45]
Role in immune response
White blood cells produce hyaluronidase to move more easily through connective tissue to get to infected sites.[46]
Role in sepsis and septic shock
Plasma hyaluronic acid is elevated in sepsis and septic shock and correlate with disease severity, but the effect on mortality shows conflicting results.[47][48] Hyaluronidase, when injected into the circulation, results in the loss of glycocalyx[49] and is therefore considered as a potential endogenous sheddase.[50] However, plasma hyaluronidase activity is decreased in experimental as well as in clinical septic shock.[51] Concomitant, the endogenous hyaluronidase inhibition in plasma was increased and may explain to certain extent the decreased plasma hyaluronidase activity.[citation needed]
Role in fertilization
In mammalian
The majority of mammalian ova are covered in a layer of granulosa cells intertwined in an extracellular matrix 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.[53]
References
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- ^ "ARTG ID 27749 Hyalase 1500IU powder for injection ampoule". Therapeutic Goods Administration (TGA). Archived from the original on 29 October 2021. Retrieved 9 August 2020.
- ^ "Hyalase 1500 I.U. Powder for Solution for Injection/Infusion or Hyaluronidase 1500 I.U. Powder for Solution for Injection/Infusion - Summary of Product Characteristics (SmPC)". (emc). 12 March 2015. Retrieved 1 May 2020.
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- ^ "Drug Approval Package: Amphadase (Hyaluronidase) NDA #021665". U.S. Food and Drug Administration (FDA). 4 February 2005. Retrieved 1 May 2020.
- ^ "Hydase: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). 23 March 2020. Retrieved 1 May 2020.
- ^ "Drug Approval Package: Hylenex Recombinant (Hyaluronidase) NDA #021859". U.S. Food and Drug Administration (FDA). 3 January 2006. Retrieved 1 May 2020.
- ^ "Halozyme Therapeutics and Baxter Healthcare Corporation Announce FDA Approval of Hylenex". Archived from the original on October 18, 2007. Retrieved 2008-11-07.
- ^ "Hylenex recombinant (hyaluronidase- human recombinant injection), solution". DailyMed. 1 January 2016. Retrieved 1 May 2020.
- ^ a b c d e "HyQvia EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 1 May 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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- ^ "Hyqvia Approval Letter". U.S. Food and Drug Administration (FDA). Archived from the original on 22 July 2017. Retrieved 20 November 2015.
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- ^ "Drug Approval Package: Herceptin Hylecta". U.S. Food and Drug Administration (FDA). 17 October 2019. Retrieved 1 May 2020.
- ^ "Herceptin Hylecta- trastuzumab and hyaluronidase-oysk injection, solution". DailyMed. 13 May 2019. Retrieved 1 May 2020.
- ^ "Darzalex Faspro: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 1 May 2020.
- ^ "FDA Approves Breast Cancer Treatment That Can Be Administered At Home By Health Care Professional". U.S. Food and Drug Administration (Press release). 29 June 2020. Retrieved 29 June 2020.
- ^ "FDA approves combination of pertuzumab, trastuzumab, and hyaluronidase". U.S. Food and Drug Administration (FDA). 29 June 2020. Retrieved 29 June 2020.
- ^ "FDA approves daratumumab and hyaluronidase-fihj with pomalidomide and". U.S. Food and Drug Administration (FDA). 12 July 2021. Retrieved 12 July 2021.
This article incorporates text from this source, which is in the public domain.
- ^ "Halozyme Announces argenx Receives FDA Approval for Vyvgart Hytrulo With Enhanze for Subcutaneous Use in Generalized Myasthenia Gravis" (Press release). Halozyme Therapeutics. 20 June 2023. Retrieved 24 June 2023 – via PR Newswire.
- ^ "Argenx Announces U.S. Food and Drug Administration Approval of Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) Injection for Subcutaneous Use in Generalized Myasthenia Gravis". Argenx (Press release). 20 June 2023. Retrieved 24 June 2023.
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External links
Media related to Hyaluronidase at Wikimedia Commons
- Hyaluronidase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)