Question

Figure 16.6 The deadly nerve gas Sarin irreversibly inhibits acetycholinesterase. What effect would Sarin have on muscle contraction?

Short answer

Answer: The effect of sarin on muscle contraction is that it causes constant, uncontrolled muscle contraction due to the inhibition of acetycholinesterase. Sarin binds to the active site of acetycholinesterase, preventing the enzyme from breaking down acetylcholine, which leads to an accumulation of the neurotransmitter in the synaptic cleft. This results in continuous stimulation of the muscle cell, causing muscle spasms, paralysis, and eventually death.

Step-by-step solution

Understand the neuromuscular junction process

The neuromuscular junction is the site of communication between a motor neuron and a muscle cell. To initiate muscle contraction, the motor neuron releases the neurotransmitter acetylcholine (ACh) from its axon terminal. The ACh molecules diffuse across the synaptic cleft and bind to ACh receptors on the sarcolemma (muscle cell membrane), causing a depolarization and signaling the muscle cell to contract.

Identify the role of acetycholinesterase in muscle contraction

Acetycholinesterase is an enzyme present in the synaptic cleft. Its main function is to break down ACh molecules after they have transmitted the signal to the muscle cell. This breakdown of ACh allows the muscle cell to return to its resting state, making it ready for the next signal to contract.

Understand the effect of sarin on acetycholinesterase

Sarin is a powerful inhibitor of acetycholinesterase. When sarin enters the synaptic cleft, it binds to the active site of acetycholinesterase, preventing the enzyme from breaking down ACh molecules. This inhibition of acetycholinesterase is irreversible, meaning that the enzyme cannot regain its function.

Determine the effect of sarin on muscle contraction

Since sarin inhibits acetycholinesterase and the enzyme cannot break down ACh, the neurotransmitter accumulates in the synaptic cleft. This abundance of ACh causes continuous stimulation of the muscle cell, leading to constant depolarization and muscle contraction. The constant, uncontrolled muscle contraction can result in muscle spasms, paralysis, and eventually, death.

Key concepts

Acetylcholine

Acetylcholine (ACh) plays a crucial role in the process of muscle contraction at the neuromuscular junction. It acts as a chemical messenger that allows motor neurons to communicate with muscle cells. When a signal travels down a motor neuron, ACh is released from tiny sacs known as synaptic vesicles at the neuron's end.
The ACh molecules then cross a tiny gap called the synaptic cleft to reach the muscle cell's membrane. This interaction is essential for triggering muscle contraction, as ACh binds to receptors on the muscle cell, leading to depolarization, an electrical change that initiates muscle contraction. Without this critical neurotransmitter, our muscles would remain static and unresponsive.
However, the role of acetylcholine doesn't stop there. After fulfilling its duty, it needs to be removed quickly to ensure the muscle doesn't stay contracted. This removal allows muscles to relax and prepare for the next signal. Thus, the cycle of contraction and relaxation continues efficiently in response to our motor needs.

Enzyme Inhibition

Enzyme inhibition, particularly of an enzyme called acetylcholinesterase, directly impacts muscle contraction. Acetylcholinesterase is responsible for breaking down acetylcholine after it has performed its function.
This breakdown clears the neurotransmitter from the synaptic cleft, allowing the muscle cells to stop contracting and return to a relaxed state. When a substance inhibits this enzyme, it prevents acetylcholinesterase from carrying out its function. As a result, acetylcholine accumulates in the synaptic cleft.
The continued presence of acetylcholine keeps the receptors on the muscle cells engaged, which means the cells remain in a depolarized state. Ultimately, this enzyme inhibition disrupts the delicate balance of contraction and relaxation, leading to persistent muscle contraction and preventing the muscle from relaxing.

Muscle Contraction

Muscle contraction is a process that relies on the controlled action of neurotransmitters and enzymes at the neuromuscular junction. When acetylcholine binds to receptors on the muscle membrane, it causes an influx of ions, leading to depolarization.
This depolarization is the first step in a cascade of reactions inside the muscle fiber, including the release of calcium ions, which ultimately enables the muscle fibers to slide past one another and contract.
This biological event is crucial for any voluntary muscle movement we make, whether it’s blinking, walking, or lifting an arm. The ability to stop contraction through the breakdown of acetylcholine by acetylcholinesterase is, therefore, just as essential as the contraction itself.
A disruption in this balanced mechanism can result in muscles that contract without the ability to relax, causing spasms or, in severe cases, paralysis.

Nerve Gas Effects

The impact of nerve gases, like Sarin, stems from their ability to inhibit acetylcholinesterase irreversibly. By binding to this enzyme, Sarin stops it from breaking down acetylcholine, leading to an excess of this neurotransmitter in the synapse.
With acetylcholine unable to be cleared, the affected muscle receptors continue to be stimulated, resulting in perpetual muscle depolarization. This continuous stimulation causes the muscle to remain contracted, leading to severe effects such as spasms or complete paralysis.
The irreversible nature of this inhibition means normal muscle function can't be restored without medical intervention. In high concentrations, the effects are not limited to individual muscles but can affect the whole muscular system, including respiratory muscles, leading to life-threatening conditions.
Thus, understanding the effects of nerve gases highlights the importance of acetylcholine breakdown in maintaining muscle function and overall bodily control.