Hyaluronidase

Hyaluronidase (HAse) is a type of glycosylase widely distributed in nature and degrades hyaluronic acid (HA) by acting on β-1, 3 or β-1,4-glycosidic bonds. In addition, it also catalyzes the action of chondroitin (CS) and chondroitin sulfate to some extent. Hyaluronidase was first discovered in 1929. Scientists discovered a "diffusion factor" that promotes the spread of vaccines, dyes, and toxins in the mammalian testis and other extracts. It was subsequently identified as hyaluronidase.

Distribution

Hyaluronidase is widely found in body fluids such as animal plasma, tissue fluids, and semen, organs such as kidney, liver, spleen, and brain, animal venoms such as snake venom, lizard poison, scorpion venom, spider venom, bee venom, and ant poison, as well as some bacteria.

Mammalian Hyaluronidase

The human genome contains six hyaluronidases with similarities ranging from 33% to 42%. The current research on human hyaluronidase is mainly concentrated in Hyal-1, Hyal-2 and PH-20. Hyal-1 is highly expressed in the liver, kidney, spleen, and heart of mammals, focused on lysosomes. Hyal-1 is a 57 kDa acidic glycoprotein that catalyzes the degradation of hyaluronic acid of various molecular weights to produce tetrasaccharide products. Hyal-2 is distributed in lysosomes or anchored on blood cell membranes by glycosyl phosphatidylinositol, regulating intracellular and extracellular hyaluronan catabolism. The function of Hyal-1 and Hyal-2 in mammals is clear, Hyal-2 on the cell surface first degrades hyaluronic acid to a fragment of approximately 20 kDa, followed by Hyal-1 catalyzed sugar fragment to tetrasaccharide. PH-20 (sperm adhesion molecular 1, SPAM) protein is a multifunctional protein anchored in the membrane and is present in the testis, epididymis, female reproductive tract, thoracic, intestinal and malignant tumors. PH-20 is a multifunctional protein that has other functions in addition to hyaluronidase activity. Most commercially available hyaluronidases are extracted from mammalian testis tissue.

Animal Venom Hyaluronidase

Hyaluronidase is present in many animal venoms. The activity of hyaluronidase has been detected in the venom of bees, snakes, spiders, rose locusts, lizards and scorpions. Hyaluronidase degrades the hyaluronic acid in the perivascular matrix to make the toxin easily accessible to blood vessels, which is the key to the entry of venom into the systemic circulation from the site of injury. From the isoelectric point, hyaluronidase in animal venom is a basic protein, approximately 33-110 kDa. The hyaluronidases in bee venom are allergens that cause the body to produce IgE-mediated, fatal allergic reactions. Structural analysis of hyaluronidase in venom has important clinical significance and provides a basis for the pathological response to the venom.

Microbial Hyaluronidase

Hyaluronidase is a virulence factor in the pathogenic process of microorganisms. It is usually in direct contact with host tissues or causes pathogens to escape their defense mechanisms. Hyaluronidase degrades hyaluronic acid in the host matrix, making the host susceptible to gas gangrene, meningitis, synovitis, hyperplasia, nephritis, mycoplasmosis, periodontal disease, mastitis, pneumonia, sepsis, syphilis, toxic shock syndrome and other diseases. The high-molecular-weight hyaluronic acid in the host body is involved in immune regulation and has anti-inflammatory activity, and the hyaluronidase produced by the microorganism cleaves the high-molecular-weight hyaluronic acid contained therein into oligomeric hyaluronic acid and becomes a factor for inducing an inflammatory reaction, molding the environment for the growth of microorganisms in the host organism.

Hyaluronidase Inhibitors

Hyaluronidase is involved in physiological processes such as fertilization process, neovascularization, inflammatory reaction, wound repair, bacterial pathogenesis, and toxin diffusion. Therefore, hyaluronidase inhibitors lay the foundation for research and development of contraceptives, anti-tumor agents, and antibacterial agents. Hyaluronidase inhibitors found by current research progress can be roughly divided into 9 categories: alkaloids, antioxidants, terpenoids, flavonoids, synthetic compounds, mucopolysaccharides, fatty acids, oligosaccharides and anti-inflammatory drugs.

Applications

Hyaluronidase is widely used in many fields, such as plastic surgery, ophthalmology, internal medicine, oncology treatment, dermatology, and gynecology. There are three types of uses approved by the US FDA: (1) To improve the anesthetic effect in ophthalmic surgery. Hyaluronidase reduces the duration of anesthesia while accelerating the speed of anesthesia. (2) Addition of subcutaneous perfusion fluid. The perfusate contains physiological saline, 5% dextrose, and a small amount of hyaluronidase, and 15 U of hyaluronidase is added per 100 ml of liquid to promote liquid absorption. Common injection sites include chest cavity, abdomen, thigh, and upper arm. (3) Hyaluronidase is used to promote the reabsorption of contrast agent in urography, especially if the intravenous injection of infants or children does not achieve results.