Cholinesterases: Function & Diseases

Cholinesterases are enzymes that are formed in the liver. They are important for laboratory diagnosis.

What are cholinesterases?

Cholinesterase (ChE) is an enzyme produced within the liver. It belongs to group III of the hydrolases. Thus, the enzyme catalyzes the hydrolytic cleavage of the ester bond that occurs between the carboxy group of an organic acid and the OH group of the nutrient choline. Cholinesterase is one of the enzymes. These are special proteins that temporarily biochemically modify various building blocks in the human body. In this way, these substrates can be used for metabolic processes, among other things. If the desired effect can be achieved, the enzyme-substrate complex is subsequently dissolved.

Function, action, and tasks

Cholinesterases are supplied to the circulation via the blood. There, the enzyme searches for specific substrates so that it can separate the ester bonds of organic acids with choline. Cholinesterases can be divided into different subgroups depending on the type of acid. These include true cholinesterase (acetylcholinesterase) and nonspecific cholinesterase (pseudocholinesterase). While acetylcholinesterase is responsible for the cleavage of acetylcholine into acetate and choline, pseudocholinesterase is responsible for the cleavage of different cholinesters. The non-specific cholinesterases are detected in the blood as well as in the pancreas and the mucosa of the intestine. They can be used to prevent a reaction of acetylcholine in the organs. The most important task of cholinesterase is to regulate the interaction between muscles and nerves. Since cholinesterases are produced exclusively in the liver, they are extremely important for medical diagnostics. Thus, liver dysfunction can be evaluated with the enzymes. A correct diagnosis is not possible with the blood values determined. For this reason, doctors use the cholinesterases to monitor the progress of the disease. The most common causes of the disorder are liver inflammation such as hepatitis or tumor disease. If the cholinesterase level drops during the tests performed, this is considered an indication of a decline in enzyme production. This means a reduced functionality of the liver or liver cells. In this way, the physician determines whether the liver can still produce the important substances.

Formation, occurrence, properties and optimal values

As mentioned earlier, the production of cholinesterase occurs only in the liver. There it is produced by hepatocytes, the cells of the liver. Generally valid reference values for cholinesterase do not exist. The reason for this is its strong individual fluctuation from person to person. In addition, there is a certain dependence of the enzyme on certain factors such as gender, age and temperature. For this reason, during a follow-up test, an initial value is determined, which serves as a reference to which the physicians orient themselves for the examination. Due to the relatively long half-life, changes in enzyme activity can usually only be detected after two weeks. In medicine, certain standard values for cholinesterase apply, which are set separately for men and women. For example, in the male sex there is an upper limit of 12.9 kilo units per liter (kU/l) at a temperature of 37 degrees Celsius. The lower limit is 5.3 kU/l. For women, a differentiation is made between pregnant and non-pregnant women. If there is no pregnancy, there is an upper limit of 11.3 kilo units per liter and a lower limit of 4.3 kU/l. In pregnant women, there is an upper limit of 9.1 kU/l as well as a lower limit of 3.7 kU/l. Thus, there is a decrease in the cholinesterase value during pregnancy. Despite these established standard values, the individual case is always assessed as a matter of principle. Thus, cholinesterase values that are extremely low or high may well be normal.

Diseases and disorders

A low cholinesterase level is mostly caused by certain diseases. These primarily include chronic liver disease such as hepatitis, a liver tumor, cirrhosis, or other cancers.Other possible triggers include the use of certain drugs such as ovulation inhibitors or beta blockers, severe poisoning with paracetamol, insecticides or nerve agents, severe malnutrition, sepsis (blood poisoning) or severe infections. In some cases, a deficiency of cholinesterase is also already congenital and has no disease value. However, there is a risk when anesthetics are administered that require cleavage of the cholinesterase enzyme. For this reason, the drug must be adjusted because the breakdown of the anesthetic is slow. Establishing the level of cholinesterase is generally important before administering anesthesia. Thus, the patient is often given muscle relaxants to relax the muscles, the breakdown of which occurs through the liver. The administration of these agents suppresses the patient’s independent breathing, so that mechanical ventilation must take place. In order to accurately determine the correct dosage, the cholinesterase value is required. It provides information about the activity of the liver cells. By calculating the enzyme value, the person should be able to breathe on his own again as quickly as possible. If the cholinesterase values turn out to be too high, this has no significance for diagnostics or progress monitoring. Elevated values occur in the case of diabetes mellitus (diabetes), fatty liver, diseases of the cardiovascular system such as angina pectoris or a heart attack, and nephrotic syndrome. Other culprits include loss of protein in the intestine, hyperthyroidism, severe obesity, and Gilbert-Meulenbracht disease. Sometimes the elevated cholinesterase levels also result from hereditary characteristics.