Question

Succinylcholine is a fast-acting, short-duration muscle relaxant that is used when a tube is inserted into a patient's trachea or when a bronchoscope is used to examine the trachea and bronchi for signs of cancer. Within seconds of the administration of succinylcholine, the patient experiences muscle paralysis and is placed on a respirator while the examination proceeds. Succinylcholine is a competitive inhibitor of acetylcholinesterase, a nervous system enzyme, and this inhibition causes paralysis. However, succinylcholine is hydrolyzed by blood-serum cholinesterase, which shows broader substrate specificity than does the nervous system enzyme. Paralysis lasts until the succinylcholine is hydrolyzed by the serum cholinesterase, usually several minutes later. (a) As a safety measure, serum cholinesterase is measured before the examination takes place. Explain why this measurement is good idea. (b) What would happen to the patient if the serum cholinesterase activity were only 10 units of activity per liter rather than the normal activity of about 80 units? (c) Some patients have a mutant form of the serum cholinesterase that displays a \(K_{M}\) of \(10 \mathrm{mM},\) rather than the normal 1.4 mM. What will be the effect of this mutation on the patient?

Short answer

Measuring serum cholinesterase checks if patients can recover from paralysis. Low activity or mutant enzyme prolongs paralysis.

Step-by-step solution

Understanding the Role of Enzymes in the Process

Succinylcholine functions as a competitive inhibitor of acetylcholinesterase, leading to muscle paralysis which allows for medical procedures like bronchoscopy. Serum cholinesterase is responsible for hydrolyzing succinylcholine, enabling the return of normal muscle function.

Importance of Measuring Serum Cholinesterase Activity

Measuring serum cholinesterase before the examination ensures that the patient can effectively hydrolyze succinylcholine and regain muscle function after the procedure. Low enzyme activity could prolong paralysis and potentially cause complications.

Exploring the Effect of Low Serum Cholinesterase Activity

If serum cholinesterase activity is 10 units instead of the normal 80 units, succinylcholine hydrolysis will be slower, leading to an extended duration of paralysis. This could put the patient at risk for complications due to prolonged paralysis.

Investigating the Effect of Mutant Serum Cholinesterase

A mutant serum cholinesterase with a higher K_M of 10 mM (as opposed to the normal 1.4 mM) indicates a decreased affinity for succinylcholine. This reduced affinity means succinylcholine is hydrolyzed much more slowly, resulting in prolonged muscle paralysis.

Key concepts

Enzyme Inhibition

Enzyme inhibition is a process by which a molecule binds to an enzyme, decreasing its activity. Enzymes are biological molecules that speed up chemical reactions in our body. By blocking these, inhibitors can control the reaction speed or stop it entirely. In the context of biochemistry, there are several types of inhibition. One common type is competitive inhibition, where the inhibitor resembles the enzyme's natural substrate. This means they "compete" for the same active site on the enzyme. If the inhibitor binds to the enzyme, it prevents the true substrate from attaching, thus slowing down the enzyme's activity.

This mechanism is crucial in many biological processes, including drug action, like muscle relaxants used during surgeries, where controlling enzyme activity is vital for patient safety. Understanding how enzyme inhibition works allows scientists and doctors to manipulate it for therapeutic and medical uses.

Muscle Relaxants

Muscle relaxants are drugs that reduce tension in muscles. They are often used during surgeries or medical procedures to prevent any movement. The patient remains still, which is crucial for the precision required in procedures like intubation. One well-known example of a muscle relaxant is succinylcholine. It acts very quickly, within seconds of administration. This speed is beneficial in emergency settings where time is critical.

Muscle relaxants can work in various ways, but many of them inhibit enzymes that are responsible for muscle contractions. By blocking these enzymes, the muscles temporarily lose their ability to contract, resulting in paralysis. It's important to note that this paralysis is meant to be temporary, and monitoring must be done to ensure that these relaxants are removed from the patient's body effectively after the procedure.

Cholinesterase Activity

Cholinesterase activity involves enzymes that break down acetylcholine, a substance that transmits nerve signals. This breakdown is necessary to stop the signal and allow muscles to relax after they have contracted. In blood, there are different types of cholinesterase with varying specificities.

In medical settings, particularly those involving muscle relaxants like succinylcholine, serum cholinesterase plays a crucial role. It hydrolyzes and removes succinylcholine after it has been used to paralyze muscles. If someone has low serum cholinesterase activity, the process will be slower, and muscle paralysis may last longer than intended.

• High enzyme activity means faster breakdown.
• Low enzyme activity results in prolonged effects.

Therefore, measuring cholinesterase levels before medical procedures ensures that muscle relaxants work as expected and safely.

Succinylcholine

Succinylcholine is a synthetic compound that mimics the natural neurotransmitter acetylcholine but acts very differently in the body. As a muscle relaxant, it temporarily causes muscle paralysis by interrupting nerve impulse transmission. Succinylcholine is categorized as a competitive inhibitor, meaning it competes with acetylcholine for the same binding sites on the enzyme acetylcholinesterase.

This competition leads to a temporary cessation in nerve signaling, resulting in muscle relaxation. Succinylcholine's effects are typically short-lived due to its rapid breakdown by serum cholinesterase. However, variations in enzyme activity or genetic mutations can alter this timeline. This makes succinylcholine an invaluable tool in medicine, helping facilitate procedures that require stillness, like tracheal intubation or bronchoscopy.

Medical Procedures

Medical procedures involve intricate tasks that often require the patient to remain absolutely still, such as surgeries or examinations using instruments like bronchoscopes. Muscle relaxants like succinylcholine are used to achieve this state of stillness. It's crucial that the timing of muscle relaxation and recovery aligns with the procedure's requirements.

• Ensures precision and safety during the procedure.
• Minimizes patient discomfort.

Before administering muscle relaxants, measurements of cholinesterase levels are often taken to predict how long the muscle relaxation will last. This helps in planning the procedure effectively. If there were any enzyme deficiencies or mutations, medical staff could prepare alternatives to safeguard patient safety. Understanding these elements can significantly reduce risks during medical procedures.