Butyrylcholinesterase (BChE) deficiency is a condition related to an enzyme primarily found circulating in the blood plasma, sometimes referred to as pseudocholinesterase. This enzyme’s main biochemical activity is to break down specific types of chemical compounds known as esters, including some drugs and toxins. BChE is a type of serine hydrolase that uses the amino acid serine in its active site to facilitate the breakdown of these chemicals. Its presence in the bloodstream gives it a broad reach to metabolize substances before they can affect other parts of the body.
The Enzyme’s Normal Biological Function
Butyrylcholinesterase is produced predominantly by the liver, which then releases the enzyme into the bloodstream where it circulates widely throughout the body. The enzyme’s activity involves hydrolysis, a chemical reaction that uses water to break apart the bonds in ester compounds.
While often overshadowed by the more specific acetylcholinesterase (AChE), BChE functions as a non-specific scavenger enzyme. It helps to clear various compounds, both naturally occurring and foreign, that contain an ester bond. This broad activity contrasts with AChE, which is concentrated in nerve synapses to rapidly break down the neurotransmitter acetylcholine to terminate nerve signaling.
BChE is thought to complement the function of AChE, particularly in areas outside the nervous system or when AChE activity is compromised. By hydrolyzing choline-based esters, BChE prevents the buildup of substances that could interfere with normal nerve and muscle function.
Genetic Variations and Anesthesia Risk
The most recognized clinical consequence of BChE deficiency relates to genetic variations in the BCHE gene, which provides instructions for making the enzyme. Mutations can lead to the production of an “atypical” BChE enzyme that has significantly reduced or absent function. This inherited deficiency is typically passed down in an autosomal recessive pattern.
This genetic difference becomes critical when a patient requires general anesthesia involving the muscle relaxant succinylcholine, a choline ester drug. Succinylcholine is administered to temporarily relax skeletal muscles, including those required for breathing, often to facilitate intubation. In individuals with normal BChE, the enzyme rapidly hydrolyzes and inactivates the drug, ensuring the paralysis lasts only a few minutes.
However, in a person with atypical BChE, the enzyme cannot break down succinylcholine quickly enough. This results in the drug remaining active for a prolonged period, leading to extended muscle paralysis and the inability to breathe unassisted, a condition known as prolonged apnea.
Identifying this deficiency often relies on a blood test that measures BChE activity. Knowing about a family history of complications with general anesthesia can also signal a risk. Anesthesiologists must be aware of this genetic polymorphism so they can manage the patient’s respiratory function for an extended time or use alternative muscle relaxant agents.
Acquired Conditions That Change BChE Levels
Beyond genetic inheritance, the level and activity of butyrylcholinesterase can be significantly altered by various acquired medical conditions. Since the liver is the primary site of BChE synthesis, conditions that affect liver function frequently lead to an acquired BChE deficiency. Severe liver diseases, such as cirrhosis or acute hepatitis, can reduce the liver’s ability to produce the enzyme, causing plasma levels to fall.
Malnutrition and protein-energy wasting can also result in lower BChE levels because the necessary building blocks for protein synthesis are scarce. Furthermore, late-stage pregnancy is associated with a physiological decrease in BChE activity, although the mechanism is not fully understood.
Certain medications can also inhibit the enzyme, leading to a temporary reduction in its activity. Conversely, some conditions can cause BChE levels to rise above the normal range, such as hyperthyroidism, nephrotic syndrome, and metabolic disorders like obesity and type 2 diabetes.
Detoxification Against Environmental Toxins
A separate function of BChE is its role in protecting the body from external chemical threats, specifically organophosphate compounds. These chemicals are commonly found in agricultural pesticides, and they exert their toxic effects by irreversibly inhibiting acetylcholinesterase (AChE). BChE acts as a protective barrier in the blood before these toxins can reach the nervous system.
The BChE enzyme serves as a “sacrificial sink” or “bioscavenger” because it reacts with and binds to the organophosphate molecules in the circulation. This reaction inactivates both the toxin and the BChE enzyme. While the BChE enzyme is destroyed in the process, its inactivation has no immediate adverse effects on the body, unlike the inhibition of AChE, which can be lethal.
A significant drop in BChE activity in a patient’s blood can be a clear indicator of recent exposure to organophosphate chemicals. This detoxification role highlights BChE’s function as a biological buffer, protecting the more functionally critical enzyme, AChE, from chemical injury.