Elastases: Function & Diseases

Elastases represent a group of proteases closely related to the enzymes trypsin and chymotrypsin. They belong to the serine proteases. Nine enzymes belonging to the elastases are known to date for the human organism.

What are elastases?

Elastases are nonspecific proteases that are found in all animal and human organisms. The name comes from the fact that, among other things, they are able to break down the body’s own elastin. The elastases belong to the serine proteases. Their active center contains the so-called catalytic triad of aspartic acid, serine and histidine. Furthermore, the elastases also belong to the endoproteases. They do not degrade proteins and polypeptide chains step by step, but cleave them at specific amino acids and characteristic amino acid sequences. The protein is broken up within the peptide chain. The effect of elastases is not specific. Thus, endogenous proteins can also be broken down from elastin. Therefore, the effect of these enzymes must be limited by elastase inhibitors. Among the elastases, two forms are distinguished. Thus, there are pancreatic elastases and granulocyte elastases. As the name implies, pancreatic elastases (elastase 1) are secreted from the pancreas. Granulocyte elastase (elastase 2) is found in neutrophil granulocytes. A deficiency of elastase 1 in the stool is considered evidence of pancreatic insufficiency.

Function, effects, and roles

Elastases function to cleave peptide bonds in proteins or polypeptide chains. This results in the formation of smaller peptide chains or single amino acids. Pancreatic elastase assists the proteases trypsin and chymotrypsin in breaking down dietary proteins. It is formed in the pancreas as an inactive proenzyme (zymogen) and, after release into the small intestine, is converted into the active form by the action of trypsin. In this process, a partial chain is cleaved from the zymogen. Elastase 1 in particular cleaves the fibrous protein elastin. Elastin is a component of the connective tissue of the lungs, blood vessels and skin. Its main function in the organism is to provide support. Elastin gives shape and support to organs. Since it forms protein networks via junctions of four lysine molecules, it cannot be degraded by many proteases. However, elastase 1 has the ability to do so. Elastin components from food are broken down and can thus be further degraded to amino acids. Unfortunately, the effect of elastase is non-specific, so that it can also attack the body’s own elastin structures. For this purpose, the body forms elastin inhibitory proteins that can control the destructive effect of elastin. These proteins include α1-antitrypsin, alpha-2-macroglobulin or elafin. The second group of elastases represent granulocyte elastase as ELA-2. Their function is to degrade phagocytosed microorganisms as part of an immune response to infection. However, they also act non-specifically and attack the body’s own elastin. If the effect of elastase inhibitory proteins is limited in the process, this can lead to the destruction of lung tissue with the formation of emphysema, among other things.

Formation, occurrence, properties, and optimal values

In the human organism, elastases, regardless of their site of synthesis, are important supporters of the immune system in combating Gram-negative germs in the digestive tract, in the lungs, and on wounds. In this process, they cleave the corresponding proteins on the carboxy side of hydrophobic amino acids, which include valine, glycine and alanine. However, as already mentioned, their effect is always non-specific. The human body metabolizes approximately 500 milligrams of elastase daily. Elastase is not broken down in the body. It is excreted unchanged in the stool. The excreted amount in the stool can be used to test the function of the pancreas. It is true that chymotrypsin is also excreted in the faeces. However, the determination of elastase can be used more clearly for diagnostic purposes. Normal elastase concentration is at least 200 micrograms per gram of stool.

Diseases and disorders

A stool elastase level that is too low indicates pancreatic insufficiency. If the level is between 100 and 200 micrograms per gram of feces, it is a mild to moderate pancreatic dysfunction. Values below 100 micrograms indicate severe pancreatic insufficiency. Elastase detection in stool is a characteristic diagnostic feature of pancreatic insufficiency.This is the exocrine function of the pancreas. Insulin production may be unaffected. In pancreatic insufficiency, too few digestive enzymes are secreted. This applies to proteases as well as lipases and amylases. Many food components reach the large intestine undigested, where they are further broken down by pathogenic bacteria. The pathogenic germs can only thrive if sufficient undigested food components are still present. Putrefaction and fermentation processes develop, leading to meteorism, diarrhea and abdominal discomfort. Since fats are also no longer broken down, fatty stools may develop. The cause of pancreatic hypofunction may be due to acute or chronic pancreatitis. Pancreatitis is usually the result of self-digestion of part of the pancreas due to non-outflow of digestive juices. The pancreatic outlet may be narrowed due to tumors or gallstones. Outflow obstruction due to malformations is also possible. Prolonged chronic pancreatitis leads to long-term functional impairment of the pancreas with decreased enzyme production. If there is an elastase 2 deficiency due to a genetic defect, the immune system of the affected patient is weakened. This constantly leads to life-threatening infections. In the case of a deficiency of elastase inhibitors such as alpha-1-antitrypsin or increased activity of elastase in the case of pneumonia, lung function can be severely restricted. In the long term, this develops into emphysema. In cases of genetic alpha-1-antitrypsin deficiency, lifelong substitution therapy with genetically engineered alpha-1-antitrypsin is given.