Chymotrypsin (EC 3.4.21.1, chymotrypsins A and B, alpha-chymar ophth, avazyme, chymar, chymotest, enzeon, quimar, quimotrase, alpha-chymar, alpha-chymotrypsin A, alpha-chymotrypsin) is a digestive enzyme component of pancreatic juice acting in the duodenum, where it performs proteolysis, the breakdown of proteins and polypeptides. Chymotrypsin preferentially cleaves peptide amide bonds where the side chain of the amino acid N-terminal to the scissile amide bond (the P1 position) is a large hydrophobic amino acid (tyrosine, tryptophan, and phenylalanine). These amino acids contain an aromatic ring in their side chain that fits into a hydrophobic pocket (the S1 position) of the enzyme. It is activated in the presence of trypsin. The hydrophobic and shape complementarity between the peptide substrate P1 side chain and the enzyme S1 binding cavity accounts for the substrate specificity of this enzyme. Chymotrypsin also hydrolyzes other amide bonds in peptides at slower rates, particularly those containing leucine and methionine at the P1 position.
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, but may also occur by intra-molecular digestion. Low pH or high temperatures can also cause proteolysis non-enzymatically.
Trypsin is a serine protease from the PA clan superfamily, found in the digestive system of many vertebrates, where it hydrolyzes proteins. Trypsin is formed in the small intestine when its proenzyme form, the trypsinogen produced by the pancreas, is activated. Trypsin cuts peptide chains mainly at the carboxyl side of the amino acids lysine or arginine. It is used for numerous biotechnological processes. The process is commonly referred to as trypsin proteolysis or trypsinisation, and proteins that have been digested/treated with trypsin are said to have been trypsinized. Trypsin was discovered in 1876 by Wilhelm Kühne and was named from the Ancient Greek word for rubbing since it was first isolated by rubbing the pancreas with glycerin.
A protease is an enzyme that catalyzes proteolysis, the breakdown of proteins into smaller polypeptides or single amino acids. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functions, including digestion of ingested proteins, protein catabolism, and cell signaling.
A zymogen, also called a proenzyme, is an inactive precursor of an enzyme. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in Golgi bodies, where a specific part of the precursor enzyme is cleaved in order to activate it. The inactivating piece which is cleaved off can be a peptide unit, or can be independently folding domains comprising more than 100 residues. Although they limit the enzyme's ability, these N-terminal extensions of the enzyme or a “prosegment” often aid in the stabilization and folding of the enzyme they inhibit.
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Serine proteases fall into two broad categories based on their structure: chymotrypsin-like (trypsin-like) or subtilisin-like.
Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption by the body. Digestive enzymes are found in the digestive tracts of animals and in the tracts of carnivorous plants, where they aid in the digestion of food, as well as inside cells, especially in their lysosomes, where they function to maintain cellular survival. Digestive enzymes of diverse specificities are found in the saliva secreted by the salivary glands, in the secretions of cells lining the stomach, in the pancreatic juice secreted by pancreatic exocrine cells, and in the secretions of cells lining the small and large intestines.
Trypsinogen is the precursor form of trypsin, a digestive enzyme. It is produced by the pancreas and found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is cleaved to its active form, trypsin, by enteropeptidase, which is found in the intestinal mucosa. Once activated, the trypsin can cleave more trypsinogen into trypsin, a process called autoactivation. Trypsin cleaves the peptide bond on the carboxyl side of basic amino acids such as arginine and lysine.
Tryptase is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. Club cells contain tryptase, which is believed to be responsible for cleaving the hemagglutinin surface protein of influenza A virus, thereby activating it and causing the symptoms of flu.
Enteropeptidase is an enzyme produced by cells of the duodenum and is involved in digestion in humans and other animals. Enteropeptidase converts trypsinogen into its active form trypsin, resulting in the subsequent activation of pancreatic digestive enzymes. Absence of enteropeptidase results in intestinal digestion impairment.
A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes. An Acid-Base-Nucleophile triad is a common motif for generating a nucleophilic residue for covalent catalysis. The residues form a charge-relay network to polarise and activate the nucleophile, which attacks the substrate, forming a covalent intermediate which is then hydrolysed to release the product and regenerate free enzyme. The nucleophile is most commonly a serine or cysteine amino acid, but occasionally threonine or even selenocysteine. The 3D structure of the enzyme brings together the triad residues in a precise orientation, even though they may be far apart in the sequence.
An oxyanion hole is a pocket in the active site of an enzyme that stabilizes transition state negative charge on a deprotonated oxygen or alkoxide. The pocket typically consists of backbone amides or positively charged residues. Stabilising the transition state lowers the activation energy necessary for the reaction, and so promotes catalysis. For example, proteases such as chymotrypsin contain an oxyanion hole to stabilise the tetrahedral intermediate anion formed during proteolysis and protects substrate's negatively charged oxygen from water molecules. Additionally, it may allow for insertion or positioning of a substrate, which would suffer from steric hindrance if it could not occupy the hole. Enzymes that catalyse multi-step reactions can have multiple oxyanion holes that stabilise different transition states in the reaction.
An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. By binding to enzymes' active sites, inhibitors reduce the compatibility of substrate and enzyme and this leads to the inhibition of Enzyme-Substrate complexes' formation, preventing the catalyzation of reactions and decreasing the amount of product produced by a reaction. It can be said that as the concentration of enzyme inhibitors increases, the rate of enzyme activity decreases, and thus, the amount of product produced is inversely proportional to the concentration of inhibitor molecules. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used in pesticides. Not all molecules that bind to enzymes are inhibitors; enzyme activators bind to enzymes and increase their enzymatic activity, while enzyme substrates bind and are converted to products in the normal catalytic cycle of the enzyme.
Pancreatic elastase is a form of elastase that is produced in the acinar cells of the pancreas, initially produced as an inactive zymogen and later activated in the duodenum by trypsin. Elastases form a subfamily of serine proteases, characterized by a distinctive structure consisting of two beta barrel domains converging at the active site that hydrolyze amides and esters amongst many proteins in addition to elastin, a type of connective tissue that holds organs together. Pancreatic elastase 1 is a serine endopeptidase, a specific type of protease that has the amino acid serine at its active site. Although the recommended name is pancreatic elastase, it can also be referred to as elastase-1, pancreatopeptidase, PE, or serine elastase.
Tissue kallikrein is an enzyme. This enzyme catalyses the following chemical reaction
Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism.
Trypsin-1, also known as cationic trypsinogen, is a protein that in humans is encoded by the PRSS1 gene. Trypsin-1 is the main isoform of trypsinogen secreted by pancreas, the others are trypsin-2, and trypsin-3 (meso-trypsinogen).
Kunitz soybean trypsin inhibitor is a type of protein contained in legume seeds which functions as a protease inhibitor. Kunitz-type Soybean Trypsin Inhibitors are usually specific for either trypsin or chymotrypsin. They are thought to protect seeds against consumption by animal predators.
Alpha-lytic endopeptidase or Alpha-lytic protease is an enzyme isolated from the myxobacterium Lysobacter enzymogenes. This enzyme is a serine protease that catalyses the breakage of peptide bonds using a hydrolysis chemical reaction. Alpha-lytic protease was named based on the observed cleavage specificity for the α position of the tetrapeptide component in gram-positive bacterial cell walls (alanine). Alpha-lytic protease is also capable of digesting elastin and other proteins.
