Chymotrypsin

Digestive enzyme

Chymotrypsin

(EC 3.4.21.1, chymotrypsins A and B, alpha-chymaroft, avazym, himar, chymotest, enceon, quimar, chymotraza, alpha-chymar, alpha-chymotrypsin A, alpha-chymotrypsin) is a component of the digestive enzyme of pancreatic juice. acts in the duodenum, where it performs proteolysis, the breakdown of proteins and polypeptides. [2] Chymotrypsin preferentially cleaves peptide amide bonds where the amino acid side chain N-terminal to the scissor-shaped amide bond (P1 position) is a large hydrophobic amino acid (tyrosine, tryptophan and phenylalanine). These amino acids contain an aromatic ring on their side chain, which fits into the hydrophobic pocket (S 1 position) of the enzyme. Activated in the presence of trypsin. Hydrophobicity and shape complementarity between the side chain of the P 1 peptide substrate and the binding cavity of the S 1 enzyme explain the substrate specificity of this enzyme. [3][4] Chymotrypsin also hydrolyzes other amide bonds in peptides at a slower rate, especially those containing leucine and methionine at the P 1 position.

Structurally, it is the archetypal structure for its superfamily, the PA protease clan.

pharmachologic effect

Chymotrypsin is a proteolytic drug of protein origin. When administered intramuscularly, the drug has an anti-inflammatory effect.

When used topically, the drug activates the process of breakdown of necrotic tissues, as well as fibrous type formations (blood clots, blood clots). The drug actively dilutes sputum, exudates, and blood clots.

During exposure to the components of the product, hydrolysis of proteins occurs and the process of breakdown of those compounds that formed amino acids .

Chymotrypsin actively affects the body in diseases of the respiratory tract, in which viscous sputum is formed.

Mechanism of action and kinetics[edit]

See also: Catalytic triad

In vivo

Chymotrypsin is a proteolytic enzyme (serine protease) active in the digestive systems of many organisms.
It facilitates the cleavage of peptide bonds through a hydrolysis reaction, which, although thermodynamically favorable, proceeds extremely slowly in the absence of a catalyst. The main substrates of chymotrypsin are peptide bonds in which the amino acid at the N-terminus of the bond is tryptophan, tyrosine, phenylalanine or leucine. Like many proteases, chymotrypsin also hydrolyzes amide bonds in vitro
, which has allowed the use of substrate analogs such as N-acetyl-L-phenylalanine, para-nitrophenylamide, for enzyme assays.

Mechanism of peptide bond cleavage in α-chymotrypsin

Chymotrypsin cleaves peptide bonds by attacking the nonreactive carbonyl group with a powerful nucleophile, serine 195, located in the active site of the enzyme, which briefly becomes covalently bound to the substrate, forming an enzyme-substrate intermediate. Together with histidine 57 and aspartic acid 102, this serine residue forms the catalytic triad of the active site.

These results are based on inhibition assays and a study of the cleavage kinetics of the above substrate using the fact that the enzyme-substrate intermediate p -nitrophenolate is yellow in color, allowing its concentration to be measured by measuring light absorbance at 410 nm.

The reaction of chymotrypsin with its substrate was found to occur in two stages: an initial "burst" phase at the start of the reaction and a stationary phase according to Michaelis–Menten kinetics. The mechanism of action of chymotrypsin explains this by the fact that hydrolysis occurs in two stages. First, acylation of the substrate to form an acyl enzyme intermediate, and then deacylation to return the enzyme to its original state. This occurs due to the coordinated action of the three amino acid residues of the catalytic triad. [5] The aspartate hydrogen binds to the N-δ hydrogen of histidine, increasing the pKa of its ε-nitrogen, thereby making it capable of deprotonating serine. This deprotonation allows the serine side chain to act as a nucleophile and bind to the electron-deficient carbonyl carbon of the protein backbone. The ionization of carbonyl oxygen is stabilized by the formation of two hydrogen bonds with adjacent backbone N-hydrogen atoms. This occurs in the oxyanion hole. This forms a tetrahedral adduct and breaks the peptide bond. An acyl enzyme intermediate bound to serine is formed, and the newly formed amino terminus of the cleaved protein can dissociate. In the second stage of the reaction, the water molecule is activated by the basic histidine and acts as a nucleophile. The oxygen in water attacks the carbonyl carbon of the acyl group bound to the serine, leading to the formation of a second tetrahedral adduct, regeneration of the serine -OH group and the release of a proton, as well as a protein fragment with a newly formed carboxyl terminus[5]

Indications for use

Chymotrypsin is prescribed to patients for the following diseases and conditions:

• periodontal disease in inflammatory-dystrophic form;
• thrombophlebitis;
• sinusitis;
• osteomyelitis;
• iridocyclitis, iritis;
• otitis;
• bronchitis , tracheitis ;
• cataract extraction.

Contraindications

People who have the following conditions or illnesses should not take this drug:

• intolerance to the components of the drug;
• decompensated forms of tuberculosis ;
• decaying malignant tumors;
• bleeding wounds;
• cirrhosis of the liver;
• infectious hepatitis;
• hemorrhagic diathesis;
• pancreatitis;
• emphysema ;
• heart failure;
• respiratory failure.

Side effects

The following negative effects are likely when taking Chymotrypsin:

• burning in the place where the product was applied;
• allergic manifestations;
• tachycardia;
• swelling and irritation of the conjunctiva;
• bleeding from healing areas;
• pain at the injection site;
• slight increase in body temperature.

During administration, substances with a histamine-like effect may be released into the cavities.

Instructions for use of Chymotrypsin (Method and dosage)

The instructions for use of Chymotrypsin stipulate that initially, before use, it is necessary to dilute the product: for this, 0.005 g of powder should be diluted in 0.5-2% novocaine solution or 1-2 ml of isotonic sodium chloride . The resulting solution should be injected deeply into the gluteal muscle.

Adult patients should receive 0.0025 g once daily. As a rule, the course of treatment includes 6-15 injections. A more detailed treatment regimen should be prescribed by the attending physician individually.

For patients with respiratory diseases, Chymotrypsin is administered intramuscularly once a day at a dose of 5-10 mg. Therapy lasts from 12 to 14 days.

For the purpose of prevention and antibacterial treatment, pleural administration of 30 mg once a day is practiced.

Patients with thrombophlebitis need to take 10 mg of the drug intramuscularly for ten days.

When treating inflammatory phenomena and infectious diseases of the sensory organs, 1 ml of Chymotrypsin is instilled onto the mucous membranes with the addition of 1% novocaine twice a day.

The use of this medicine locally is carried out as follows: the product is applied to sterile napkins, after which the napkin must be applied to the site of the lesion or to a purulent wound. In this case, Chymotrypsin (20-40 mg) is used, dissolved in 10 ml of procaine . Therapy continues for ten days.

To prevent complications after operations, daily intramuscular injection of 5-10 mg of the drug is carried out. You need to start treatment 5 days before surgery, after which the medicine is administered for another 3-4 days.

In the case of purulent sinusitis, a solution of 5-10 mg of medication in 3-5 ml of saline solution should be injected into the maxillary cavity. For patients with otitis media, it is recommended to instill 0.5 - 1 ml of a 0.1% saline solution.

Isoenzymes [edit]

special instructions

It should be remembered when using Chymotrypsin that this is a remedy that cannot be applied to ulcerated malignant tumors, or inject the solution into bleeding cavities.

It cannot be administered intravenously.

If the drug is administered to people with severe tuberculosis, it should be done carefully, starting with very low doses. After taking antihistamines, you need to take a preventive course to remove them from the body.

People who drive vehicles or work with dangerous machinery during treatment with Chymotrypsin should be careful.

Analogs

Level 4 ATC code matches:
Ronidaza

Chymopsin

Collalysin

Trypsin

Iruksol

Ribonuclease

There are a number of similar drugs with the same active substance and similar pharmacological properties.

These medications are: Collalysin , Himopsin , Daltsex-Trypsin , Lysoamidase , Collitin , Pax-Trypsin .

There is also the drug Parapran with Chymotrypsin - a bandage for topical use.

Links[edit]

1. PDB: 1CHG; Freer ST, Kraut J, Robertus JD, Wright HT, Xuong NH (April 1970). "Chymotrypsinogen: 2.5 angstrom crystal structure, comparison with alpha-chymotrypsin, and implications for zymogen activation." Biochemistry
   .
   9
   (9): 1997–2009. DOI: 10.1021/bi00811a022. PMID 5442169.
2. Jump up
   ↑ Wilcox P.E. (1970).
   "[5] Chymotrypsinogens - chymotrypsins." Chymotrypsinogens - chymotrypsins
   .
   Methods in enzymology. 19
   . pp. 64–108. DOI: 10.1016/0076-6879(70)19007-0. ISBN 978-0-12-181881-4.
3. ↑
   Appel W (December 1986).
   "Chymotrypsin: molecular and catalytic properties". Clin. Biochem
   .
   19
   (6): 317–22. DOI: 10.1016/S0009-9120 (86) 80002-9. PMID 3555886.
4. Jump up
   ↑ Berger A, Schechter I (February 1970).
   "Mapping the active site of papain using peptide substrates and inhibitors". Philosophy Per. R. Soc. London. B Biol. Sci
   .
   257
   (813):249–64. Bibcode: 1970RSPTB.257..249B. DOI: 10.1098/rstb.1970.0024. PMID 4399049. S2CID 6877875.
5. ^ ab Petsko, Grigory; Ringe, Dagmar (2009). Structure and function of proteins
   . Oxford: Oxford University Press. pp. 78–79. ISBN 978-0-19-955684-7.

Chymotrypsin price, where to buy

The price of Chymotrypsin averages from 490 to 550 rubles per 10 mg bottle.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine
• Online pharmacies in KazakhstanKazakhstan

ZdravCity

• PARAPRAN wound stimulating dressing with chymotrypsin 7.5×10 cm 30 pcs. Biotekfarm/New Dressings materials
  1965 rub. order
• Chymotrypsin lyof. d/prig. r-ra d/in., place. and outside approx. 10mg vial. No. 10 Samson-Med LLC

  914 RUR order

• “Parapran” dressing with chymotrypsin 5x7.5 cm 5 pcs. Biotekfarm/New Dressing materials

  RUB 334 order

• Chymotrypsin lyof. d/prig. r-ra d/in., place. and outside approx. 10mg vial. No. 5 Samson-Med LLC

  516 RUR order

Pharmacy Dialogue

• Chymotrypsin (vial 10 mg No. 10) Samson-med LLC

  RUB 874 order

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Pharmacy24

• Chymotrypsin 0.01 g No. 10 lyophilisate for the preparation of solution for injection TOV FZ BIOPHARMA, Ukraine / PrAT Biopharma, Ukraine
  165 UAH order

PaniPharmacy

• Chymotrypsin ampoule Chymotrypsin crystalline pore. d/in 0.01g amp. No. 10 Ukraine, Biopharma CJSC

  149 UAH order

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Activation [edit]

Chymotrypsin is synthesized in the pancreas by protein biosynthesis as a precursor called chymotrypsinogen, which is enzymatically inactive. Trypsin activates chymotrypsinogen by cleaving peptide bonds at positions Arg15 - Ile16 and produces π-chymotrypsin. In turn, the amine group (-NH3 + ) of the Ile16 residue interacts with the side chain of Asp194, creating an “oxyanion hole” and a hydrophobic “S1 pocket”. Moreover, chymotrypsin causes its own activation by cleavage at positions 14-15, 146-147 and 148-149, producing α-chymotrypsin (which is more active and stable than π-chymotrypsin). [ Edit

] The resulting molecule is a tri-polypeptide molecule connected to each other by disulfide bonds.