Chymotrypsin, also known as chymase, is a proteolytic enzyme extracted from bovine or porcine pancreas and has the function of an endopeptidase. Chymotrypsin hydrolyzes carboxyl-terminal aromatic amino acids (tyrosine, tryptophan, leucine) or hydrophobic residues such as methionine by cleaving the carboxy-terminal peptide chain of tyrosine and phenylalanine in the peptide chain of the protein. Chymotrypsin can decompose fibrin coagulation at inflammation sites, promote the coagulation of blood clots, promote the decomposition of purulent secretions, and necrotic tissue, thereby purifying wounds, regenerating granulation tissue, and promoting wound healing. The clinical applications of chymotrypsin in ophthalmology and dermatology has been confirmed, which can reduce local secretion and edema.
Human chymotrypsin is a glycoprotein with a molecular weight of 29,000. The two peptide chains are connected by three disulfide bonds and have the same conserved sequence as serine proteases. They are mainly distributed in connective tissues such as cardiovascular, skin, and bronchi. The optimum pH value of chymotrypsin is 8 to 9, and the main substrates are Ang I and neurotensin. The activity of chymotrypsin can be antagonized by chymotrypsin inhibitors and legume trypsin inhibitors. Chymotrypsin is associated with neurogenic inflammation, submucosal glandular secretion, parasite clearance, vasoactive metabolism, and extracellular matrix catabolism of lipoproteins.
The human cardiac chymotrypsin is a single-copy gene expression, whose gene is about 3kb in length and has 5 coding regions and 4 introns. The two ends are 5' and 3' untranslated regions, respectively. The first coding region is 58 bp. In an open reading frame, it encodes the first 19 amino acids of the mature enzyme precursor. The second, third, fourth, and fifth coding regions are 151, 136, 255, and 141 bp, encoding 2 to 49, 50 to 94, 95 to 179, and 180 to 226 amino acids, respectively. The amino acid residues His45, Asp89, and Ser182 that constitute the catalytically active site are located in the second, third, and fifth coding regions, respectively. The five coding regions were separated by four introns each having a length of 672, 742, 186, and 368 bp.
Mammalian chymotrypsin is divided into two types: α-chymotrypsin and β-chymotrypsin. Different animal chymotrypsin have different ways to degrade Ang I. Voles, monkeys, and human chymotrypsin are α-chymotrypsin (Ang II-generating enzyme), which cleaves peptide bonds between Ang I Phe8-His9 to generate Ang II. The rat chymotrypsin is a β-chymotrypsin (angiotensin-peptidase) that cleaves peptide bonds between Ang I Tyr4-Ile5 to form inactive peptides. Studies found that human lung, aorta, cardiac Ang II production mainly through the chymotrypsin pathway; dog, hamster aorta and heart Ang II production mainly through the chymotrypsin pathway, the lungs mainly through the ACE pathway; rabbit heart Ang II production mainly through ACE pathways, aorta and lungs Ang II production mainly through both ACE and chymotrypsin pathways.
Studies have found that most of the Ang II in human heart (greater than 80%) and aorta (greater than 60%) are produced by mast cell chymotrypsin. Mast cells are stimulated to release chymotrypsin localized in the myocardial cell mesenchyme. Ventricular chymotrypsin is three times that of the atria and there is no significant difference between the two chambers. Ang II produced by the ACE pathway accounted for only a small fraction (about 11%). The production of Ang II by chymotrypsin and other serine proteases was more efficient and more specific than by ACE. Unlike cardiac chymotrypsin localized in endothelial cells, vasospasm is mainly present in the outer membrane. Most of the Ang II production (82%) in the normal human aorta is chymotrypsin-dependent. When the blood vessel is damaged, mast cells in the wall of the blood vessel and in the atherosclerotic plaque will increase, leading to an increase of in Ang II the local lesion. Most of the Ang II production (90%) in the aorta of atherosclerotic patients is also chymotrypsin dependent.
Chymotrypsin can cleave the peptide chains of protein macromolecules into smaller molecular weight peptides, or act on the peptide ends of protein molecules to separate amino acids. Through this action, fibrin and mucin can be hydrolyzed into polypeptides or amino acids in the sputum, making the viscous sputum liquefied and easy to cough out. It is effective for purulent or non-purulent sputum. In addition, chymotrypsin can relax the ciliary ligament and dissolve the protein structure of certain tissues in the eye. Chymotrypsin also promotes the penetration of antibiotics and chemotherapeutic drugs into the lesions. Chymotrypsin can also be used to treat acne. Chymotrypsin improves tissue permeability, inhibits inflammatory reactions, and dissolves exudates and necrotic tissues, which can improve acne symptoms. Chymotrypsin can also treat infertility. It has been found that there are many factors involved in the process of semen liquefaction, of which the most important factors are enzymes. α-chymotrypsin can significantly shorten the liquefaction time of semen and reduce its viscosity, but it has no obvious effect on sperm activity.