Acetylcholinesterase: Reaction & Mechanism of Action

Instructor: Laura Foist

Laura has a Masters of Science in Food Science and Human Nutrition and has taught college Science.

Acetylcholinesterase is one of the fastest enzymes in the body. In this lesson, we will learn what it does and the mechanism by which the reaction occurs.

Sending Messages to the Muscles

Going about your day-to-day life, you walk around, you pick up objects, and you open doors. We don't typically stop to think about everything that our body is doing every single day. But how do your legs know to move, how do they know when to stop moving? How does your hand pick up and then later release the pen you used to write notes? The brain is able to send signals through the nervous system. One of the neurotransmitters in the nervous system, acetylcholine transfers the signals from the nervous system to your muscles, telling them to contract, this allows us to move.

But, if the acetylcholine neurotransmitters stayed around then they would get in the way of new messages to the muscles. So they must be quickly destroyed to prevent this interference. Acetylcholinesterase is the enzyme that breaks down the acetylcholine as soon as it completes its message to the muscles. This reaction needs to happen quickly, and thus this enzyme facilitates one of the fastest reactions in the body - breaking up the molecule in about 80 microseconds. Do you know how long a microsecond is? There are a million microseconds in a single second! Just think about it, in 80 millionths of a second the enzyme has already broken apart the acetylcholine!

This reaction proceeds by breaking the acetylcholine into acetic acid and choline. These pieces can then be used to make new acetylcholine neurotransmitters.

Acetylcholinesterase Mechanism and Active Site

The active site of acetylcholinesterase contains a serine (at residue 203), a glutamic acid (at residue 334), and a histidine (at residue 447).

The active site of acetylcholinesterase contains a glutamic acid, serine, and histidine
Active site

The general reaction mechanism proceeds by first having the serine bind to the acetylcholine. It binds to the acetyl group on the acetylcholine, breaking the bond between the acetyl group and the choline group. This releases choline.

Water can then replace the acetyl group attached to the serine, releasing the acetyl group and reforming serine.

This reaction occurs in two steps. First, the choline is broken from the acetyl, then the acetyl is broken off from the serine

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