HYALURONIDASE (gialuronatglikanogidrolaza) — the enzyme catalyzing reactions of hydrolytic decomposition and a depolymerization of hyaluronic acid and related connections by it. In classification of enzymes G. two numbers are assigned: KF 3.2.1. 35 and KF 3. 2. 1. 36 that is explained by type of the communication split by it in a molecule hyaluronic to - you: beta (1 — 4) - or beta (1 — 3) respectively.
Are eurysynusic in wildlife. At mammals this enzyme contains practically in all bodies and fabrics, seed plants and ovaries are richest with it. Is present also at plasma membranes of disease-producing bacteria: pneumococci, stafilokokk and streptococci And, In and With, diphtheritic sticks, some activators of a mephitic gangrene (Cl. welchii, Cl. septicum, Cl. oedematiens), and also at the cholera vibrio and other microorganisms some of the parasitizing worms, in particular Schistosoma mansoni, in poison of bees, snakes etc.
Follows from the fact of a wide spread occurance of G. that it carries out the important biological role connected with change of permeability of fabrics, extent of their hydration, transport of water and various ions. An essential role is played by G. in processes of disintegration of various fibrillar structures, in the course of fertilization etc. Emergence in blood serum of antigens on bacterial hyaluronidases is one of signs of artificial immunity. Seed plants (testicles) of bulls and ovaries of pigs are used for laboratory and industrial receiving enzyme. Despite multistage methods of purification of enzyme to receive drugs of hyaluronidase, free from impurity of proteolytic enzymes and p-glucuronidases, it was not possible yet. Therefore, as a rule, all medical supplies of hyaluronidases contain a nek-swarm amount of these enzymes that needs to be considered during the use of such drugs.
The testicular G. representing the glycoprotein containing in a glyconew part of a molecule 5% of mannose and 2,17% of N-atsetilglyukozamina is most studied; pier. weight (weight) of enzyme 61 000.
Optimum pH values for G. depend on a source of receiving enzyme and on a method of definition of its activity. E.g., the optimum of pH for testicular G. and G. from Clostridium welchii determined by reduction of viscosity of solution hyaluronic to - you, is at 7,0 and 6,0 respectively; the optimum pH values determined by the same method for streptococcal and staphylococcal G. are equal 5,5 and 6,6 respectively.
The optimum pH values for bacterial G. determined by accumulation of reducing sugars are equal: for streptococcal G. — 5,6 and 7,1, for staphylococcal G. — 5,6 and for enzyme from Clostridium welchii — 5,7; the optimum of pH for testicular G. determined by the same method is equal 4,4, and for pneumococcal — 5,6 — 5,8. Thus, practically only for G. from C1, welchii the optimum pH value does not depend on a method of definition of activity of enzyme.
G.'s action on hyaluronic to - that comes down to two processes: quickly proceeding depolymerization (see. Polymerization ) and to slower to hydrolysis (see), as a result to-rogo in the reactionary environment free N-atsetilglyukozamin and D-glucuronic to - that collect. Quantitatively degree of hydrolysis is estimated on increase in content of reducing sugars, and degree of a depolymerization — on reduction of viscosity of solution.
Pneumococcal G., e.g., almost completely hydrolyzes substrate to monosaccharides, and testicular G. for the same time hydrolyzes substrate only for 50%, but reduces mud viscosity twice quicker, than bacterial.
As for specific aminopolisakharidazny activity of G., testicular enzyme decomposes hyaluronic to - that and hondroitinsulfata And yes In hl. obr. to tetrasakharid, and bacterial G. decomposes hyaluronic to - that generally to disaccharides. Hondroitinsulfat And is hydrolyzed by bacterial G. if his sulphatic group leaves previously by means of soft acid hydrolysis. Enzymatic activity of G. is stimulated with cysteine, protamin, NaCl, ions of Mg 2+ and Sa 2+ . Ions of some metals (Fe 3+ , Cu 2+ , Zn 2+ ) inhibit hyaluronidase.
G.'s ability to increase permeability of fabrics facilitates to disease-producing bacteria penetration in the macroorganism struck by them. Bacterial G. promotes distribution of microbes, however between G.'s activity and an invazionnost of certain strains of causative organisms, e.g. Cl. welchii and Streptococcus pyogenes, does not exist full parallelism and direct dependence (so, the separate strains of golden staphylococcus forming G. in a large number possess very small invazionnost).
In order that certain species of microorganisms formed in the cells hyaluronidase, presence hyaluronic to - you in culture medium it is not obligatory since G.'s education by microorganisms can induce N-acetyl a glycosamine or D-glucuronic to - that. Favorable conditions for development of separate types of a hemolitic streptococcus are created in the presence of products of euzymatic disintegration hyaluronic to - you under the influence of G. that can burden an infection.
Hyaluronidase as drug
Drugs G. are widely used as remedies for acceleration of absorption of liquid at dehydration of an organism, acceleration of effect of the anesthetizing substances, a rassasyvaniye of the cicatricial fabric which is formed on site various injuries, etc.
From drugs G. in medical practice apply the lidaza and a ronidaza received from seed plants of cattle.
Lidaza (Lidasum; synonym: Hyaluronidasum, Hyalase, Hyalidase, etc.) — light yellow or zolotistozhelty porous weight, easily water soluble, apply to parenteral administration. Solution of a lidaza enter near the space of defeat for skin or under rubtsovo the changed fabrics. Injections make daily or every other day, a course of treatment — 6 — 15 injections on 0,1 g in 1 ml of 0,5% of solution of novocaine.
The main indications for use of a lidaza are contractures of joints, hems after burns and operations, an ankylosing spondylarthritis, hematomas. Lech. the effect is shown by a softening of hems, increase in mobility in joints, elimination or reduction of contractures, a rassasyvaniye of hematomas. Treatment is more effective in initial stages of process. Drug gives effect at treatment of common forms of a scleroderma. Lidaza is used also in ophthalmology — for the purpose of receiving thinner hem in affected areas of a cornea, and also at treatment of a keratitis (in a conjunctival sac dig in 0,1% solution along with use of antibacterial drugs). At retinopathies the drug is administered under skin of a temple, at vitreous hemorrhages — under a conjunctiva and retrobulbarno. At fresh hemorrhages the lidaza should not be applied.
Lidaza is applied also to acceleration of absorption of the medicinal substances entered under skin or intramusculary (mestnoanesteziruyushchy means, isotonic solutions).
At use of a lidaza there can be allergic skin reactions. As contraindications to use serve malignant new growths, tuberculosis and other infectious diseases and inflammatory processes.
Form of release: ampoules on 0,1 g of sterile nonvolatile solid. Before the use contents of an ampoule are dissolved usually in 1 ml of 0,5% of solution of novocaine. Keep in the soldered ampoules in the protected from light, cool place.
Ronidaza (Ronidasum) — the drug intended only for the outside use. Receive from seed plants of cattle. Powder of grayish-yellow color with a specific smell.
Apply at treatment of hems (burn, postoperative, keloid), palmar fibromatoses (initial stages), contractures and rigidity of joints after inflammatory processes or injuries with hemorrhages in soft tissues, by preparation for kozhnoplastichesky operations for cicatricial styazheniye, at hron, a tendovaginitis, at it is long not healing wounds.
Powder of a ronidaza is applied on the sterile gauze napkin moisturized with sterile physiological solution put in 4 — 5 layers, to-ruyu imposed on an affected area, covered with wax paper and fixed a soft bandage. The amount of drug depends on the area of defeat (0,5 g and more on one procedure). It is possible to leave a bandage for 16 — 18 hour. During the drying of a bandage it is humidified again and add the same quantity of a ronidaza. Procedures are appointed daily within 15 — 60 days. At prolonged use do breaks for 3 — 4 days after each two weeks of treatment. At treatment it is long not healing wounds a napkin moisten with the physiological solution containing 10 000 — 20 000 PIECES of benzylpenicillin in 1 ml.
During treatment the irritation of skin which is quickly passing at a short-term break in treatment is sometimes observed.
Form of release: hermetically the corked bottles on 5 g of drug. Keep in the place protected from light at the room temperature.
Bibliography: Goryunova T. E., etc. Activity of hyaluronidase in functionally various zones of renal tissue of white rats and rabbits, Izv. Sibirsk. otd. Academy of Sciences of the USSR, It is gray. biol, sciences, No. 10, century 2, page 155, 1975, bibliogr.; Ivanova L. N., Goryunov T. E. iklimovav. P. Aktivnost of fabric hyaluronidase in a night of white rats in the conditions of dehydration and effect of exogenous antidiuretic hormone, Dokl. Academy of Sciences of the USSR, t. 224, No. 5, page 1209, 1975, bibliogr.; In about 1 1 e t A. J., Bonner W. M. a. Nance J. L. The presence of hyaluronidase in varions mammalian tissues, J. biol. Chem., v. 238; p. 3522, 1963; Borders Ch. L. a. Raftery M. A. Purification and partial characterization of testicular hyaluronidase, ibid., v. 243, p. 3756, 1968; T a n Y. H. a. Bo wnese J. M. Canine submandibular-gland hyaluronidase, Biochem. J., v. 110, p. 9, 1968, bibliogr.