The hyaluronidases (EC The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme 3.2.1.35) are a family of enzymes Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at significant rates. Since enzymes are selective for their that degrade hyaluronic acid Hyaluronan is an anionic, non-sulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans in that it is unsulphated, forms in the plasma membrane instead of the Golgi and can be very large with its molecular weight often reaching the millions. One of the chief.

In humans, there are six associated genes, including HYAL1, HYAL2, HYAL3, and PH-20/SPAM1.[1]

Contents

Use as a drug

By catalyzing Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations. Catalysts that speed the reaction are called positive the hydrolysis Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations (H+) (conventionally referred to as protons) and hydroxide anions (OH−) in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization. Such polymer of hyaluronic acid Hyaluronan is an anionic, non-sulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans in that it is unsulphated, forms in the plasma membrane instead of the Golgi and can be very large with its molecular weight often reaching the millions. One of the chief, a major constituent of the interstitial barrier, hyaluronidase lowers the viscosity Viscosity describes a fluid's internal resistance to flow and may be thought of as a measure of fluid friction. For example, high-viscosity felsic magma will create a tall, steep stratovolcano, because it cannot flow far before it cools, while low-viscosity mafic lava will create a wide, shallow-sloped shield volcano. All real fluids have some of hyaluronic acid, thereby increasing tissue Tissue is a cellular organizational level intermediate between cells and a complete organism. Hence, a tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. Organs are then formed by the functional grouping together of multiple tissues permeability. It is, therefore, used in medicine in conjunction with other drugs A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease to speed their dispersion and delivery. The most common application is in ophthalmic surgery Surgery is a medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, to help improve bodily function or appearance, and sometimes for religious reasons. An act of performing surgery may be called a surgical procedure, operation, or simply, in combination with local anesthetics A local anesthetic is a drug that causes reversible local anesthesia and a loss of nociception. When it is used on specific nerve pathways , effects such as analgesia (loss of pain sensation) and paralysis (loss of muscle power) can be achieved. It also increases the absorption rate of parenteral Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins fluids given by hypodermoclysis Hypodermoclysis, which can also be called interstitial infusion or subcutaneous infusion, is the subcutaneous administration of fluids to the body. This would often be in the form of a saline or glucose solution, and is an adjunct in subcutaneous 1. Hair Shaft 2. Stratum Corneum 3. Pigment Layer 4. Stratum Spinosum 5. Stratum Basale 6. Arrector Pili Muscle 7. Sebaceous Gland 8. Hair Follicle 9. Papilla of Hair 10. Nerve Fiber 11. Sweat Gland 12. Pacinian Corpuscle 13. Artery 14. Vein 15. Sensory Nerve ending 16. Dermal Papillary 17. Sweat Pore urography for improving resorption of radiopaque agents. Hyalurodinase is also used for extravasation of hyperosmolar solutions. Usually a 0.2 ml dose of the drug is injected around the area of extravasation. A total of 1 ml is used.

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 Thiomersal (C9H9HgNaO2S), or sodium ethylmercurithiosalicylate, commonly known in the United States as thimerosal, is an organomercury compound (approximately 49% mercury by weight) used as an antiseptic and antifungal agent-free" animal-derived hyaluronidase, Vitrase (ISTA 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).[2]

Role in cancer metastasis

Hyaluronidases may play a role in cancer metastasis. It has been hypothesized that by helping degrade the extracellular matrix In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals (ECM) surrounding the tumor, hyaluronidases help cancer cells escape from primary tumor masses. Hyaluronidases are also thought play a role in the process of angiogenesis Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for new blood vessel formation by splitting off existing ones, although most hyaluronidase preparations are contaminated with large amounts of angiogeneic growth factors.[3] As previously mentioned, there are six hyaluronidase genes in the human genome, four of which can express active hyaluronidases.

Pathogenic production

Some bacteria, such as Staphylococcus aureus Staphylococcus aureus is the most common cause of staph infections. It is a spherical bacterium, frequently part of the skin flora found in the nose and on skin. About 20% of the population are long-term carriers of S. aureus. S. aureus can cause a range of illnesses from minor skin infections, such as pimples, impetigo (may also be caused by, Streptococcus pyogenes Streptococcus pyogenes is a spherical gram-positive bacterium that grows in long chains and is the cause of Group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S. pyogenes typically produces large zones of beta-hemolysis when cultured on blood agar plates and are therefore also called Group A (,[4] and Clostridium perfringens Clostridium perfringens is a Gram-positive, rod-shaped, anaerobic, spore-forming bacterium of the genus Clostridium. C. perfringens is ubiquitous in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates, insects, and soil,[5] produce hyaluronidase as a means of using hyaluronan as a carbon source.

Role in fertilization

In most mammalian fertilization Fertilisation , is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo. Depending on the animal species, the process can occur within the body of the female in internal fertilisation, or outside in the case of external, hyaluronidase is released by the acrosome The acrosome is an organelle that develops over the anterior half of the head in the spermatozoa of many animals. It is a cap-like structure derived from the Golgi apparatus. Acrosome formation is completed during testicular maturation. In Eutherian mammals the acrosome contains digestive enzymes (including hyaluronidase and acrosin). These of the sperm cell after it has reached the oocyte An oocyte, ovocyte, or rarely ocyte, is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell which undergoes a mitotic division to form an oogonium. During oogenesis the, by digesting proteins in the zona pellucida The zona pellucida is a glycoprotein membrane surrounding the plasma membrane of an oocyte. It is a vital constitutive part of the latter, external but not extraneous to it. The zona pellucida first appears in multilaminar primary oocytes, thus enabling conception Fertilisation , is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo. Depending on the animal species, the process can occur within the body of the female in internal fertilisation, or outside in the case of external.

Majority of mammalian ova are covered in a layer of granulosa cells intertwined in an ECM that contains a high concentration of hyaluronic acid. 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.[6]

References

  1. ^ 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. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 11731267. http://linkinghub.elsevier.com/retrieve/pii/S0945-053X(01)00172-X.
  2. ^ "Halozyme Therapeutics and Baxter Healthcare Corporation Announce FDA Approval of Hylenex". http://www.baxter.com/about_baxter/news_room/news_releases/2005/12-05-05-hylenex.html. Retrieved 2008-11-07.
  3. ^ <Int J Cancer. 2002 Feb 10;97(5):601-7>
  4. ^ 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 A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1128/IAI.74.1.40-48.2006. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 16368955. PMC PubMed Central is a free digital database of full-text scientific literature in biomedical and life sciences. It grew from the online Entrez PubMed biomedical literature search system. PubMed Central was developed by the U.S. National Library of Medicine as an online archive of biomedical journal articles 1346594. http://iai.asm.org/cgi/pmidlookup?view=long&pmid=16368955.
  5. ^ 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 A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1046/j.1472-765x.2000.00693.x. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 10747251. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0266-8254&date=2000&volume=30&issue=3&spage=203.
  6. ^ Alberts B et al (2008) Molecular Biology of the Cell 5ed, Garland. pp:1298

External links

Hydrolase In biochemistry, a hydrolase is an enzyme that catalyzes the hydrolysis of a chemical bond. For example, an enzyme that catalyzed the following reaction is a hydrolase:: sugar hydrolases (EC The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme 3.2)
3.2.1 This list contains a list of EC numbers for the third group, EC 3, hydrolases, placed in numerical order as determined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology: Glycoside hydrolases Glycoside hydrolases catalyze the hydrolysis of the glycosidic linkage to generate two smaller sugars. They are extremely common enzymes with roles in nature including degradation of biomass such as cellulose and hemicellulose, in anti-bacterial defense strategies (eg lysozyme), in pathogenesis mechanisms (eg viral neuraminidases) and in normal
Disaccharidase Sucrase/Sucrase-isomaltase/Invertase Invertase (systematic name: beta-fructofuranosidase) is an enzyme that catalyzes the hydrolysis (breakdown) of sucrose (table sugar). The resulting mixture of fructose and glucose is called inverted sugar syrup. Related to invertases are sucrases. Invertases and sucrases hydrolyze sucrose to give the same mixture of glucose and fructose · Maltase · Trehalase · Lactase Lactase , a part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers. Lactase is present predominantly along the brush border membrane of the differentiated enterocytes lining the villi of the small intestine. In humans, lactase
Glucosidases Cellulase Cellulase refers to a class of enzymes produced chiefly by fungi, bacteria, and protozoans that catalyze the cellulolysis of cellulose. However, there are also cellulases produced by other types of organisms such as plants and animals. Several different kinds of cellulases are known, which differ structurally and mechanistically. The EC number for · Alpha-glucosidase (Acid, Neutral AB, Neutral C) · Beta-glucosidase · Debranching enzyme Debranching enzymes are responsible for transferring three glucose subunits of glycogen from one parallel chain to another. This shortens one linear branch while lengthening another. Afterwards, the donator branch will contain only one glucose residue with alpha-1,6 linkage. This remaining residue is in turn cut by alpha-1,6 glucosidase. This two
Other Amylase Amylase is an enzyme that breaks starch down into sugar. Amylase is present in human saliva, where it begins the chemical process of digestion. Foods that contain much starch but little sugar, such as rice and potato, taste slightly sweet as they are chewed because amylase turns some of their starch into sugar in the mouth. The pancreas also makes (Alpha-Amylase α-Amylase is an enzyme that hydrolyses alpha-bonds of large alpha-linked polysaccharides such as starch and glycogen, yielding glucose and maltose. It is the major form of amylase found in humans and other mammals. It is also present in seeds containing starch as a food reserve, and is secreted by many fungi) · Chitinase Chitinases are digestive enzymes that break down glycosidic bonds in chitin. Because chitin composes the cell walls of fungi and exoskeletal elements of some animals , chitinases are generally found in organisms that either need to reshape their own chitin or to dissolve and digest the chitin of fungi or animals · Lysozyme Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases, enzymes that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins. Lysozyme is · Neuraminidase Neuraminidase enzymes are glycoside hydrolase enzymes which cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of influenza infection. The viral neuraminidases are frequently (NEU1, NEU2, NEU3, NEU4, Bacterial neuraminidase, Viral neuraminidase) · Galactosidases (Alpha, Beta β-galactosidase, also called beta-gal or β-gal, is a hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides. Substrates of different β-galactosidases include ganglioside GM1, lactosylceramides, lactose, and various glycoproteins. Alternate or nicknames are "beta-gal" or "β-gal". Lactase is) · alpha-Mannosidase alpha-Mannosidase is an enzyme involved in the cleavage of the alpha form of mannose. It can be utilized in experiments that determine the effects of the presence or absence of mannose on specific molecules, such as recombinant proteins that are used in vaccine development · Glucuronidase Beta-glucuronidases are members of the glycosidase family of enzymes that catalyze breakdown of complex carbohydrates. Human β-glucuronidase is a type of glucuronidase that catalyzes hydrolysis of β-D-glucuronic acid residues from the non-reducing end of mucopolysaccharides (also referred to as glycosaminoglycans) such as heparan sulfate. Human · Hyaluronidase · Pullulanase · Glucocerebrosidase · Galactosylceramidase · Alpha-N-acetylgalactosaminidase · Alpha-N-acetylglucosaminidase · Fucosidase Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Different phenotypes include clinical features such as neurologic deterioration, growth retardation, visceromegaly, and seizures in a severe early form; coarse facial features, angiokeratoma corporis · Hexosaminidase (HEXA, HEXB) · Iduronidase · Maltase-glucoamylase
3.2.2 This list contains a list of EC numbers for the third group, EC 3, hydrolases, placed in numerical order as determined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology: Hydrolysing N-Glycosyl compounds DNA glycosylases: Oxoguanine glycosylase

Categories: EC 3.2.1

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