What is Choline Acetyltransferase?

Leo Zimmermann

Choline acetyltransferase is an enzyme produced in the brain. This enzyme is responsible for producing the neurotransmitter acetylcholine, which it does by joining choline and acetate. Acetylcholine is important for functions such as muscle contraction, regulating heart rate and learning. Choline acetyltransferase performs this operation inside cholinergic neurons, generating a supply of acetylcholine to release into the synapse when the neuron is activated.

Cells make choline acetyltransferase in the rough endoplasmic reticulum.
Cells make choline acetyltransferase in the rough endoplasmic reticulum.

Cells manufacture choline acetyltransferase in the rough endoplasmic reticulum, contained in the cell body of a neuron. Once produced, the enzyme moves slowly through microtubules running through the axon, the long part of a neuron through which electrical signals travel. Eventually the molecule arrives at the axon terminal, the part of the neuron closest to the synapse. Here, it begins to produce acetylcholine.

The cholingeric system is responsible for cigarette addiction.
The cholingeric system is responsible for cigarette addiction.

A large enzyme called acetyl coenzyme A (acetyl-CoA) plays an important role in the process. Acetyl-CoA supplies acetate groups to chemical reactions occurring throughout the body, most notably the citric acid cycle used by every cell in the process of metabolism. Acetyl-CoA also binds to choline acetyltransferase. When choline arrives at a nearby slot, it is attached to the acetate group, creating acetylcholine. Coenzyme A is released as a byproduct and is free to bind to a new acetate group.

The result is acetylcholine. Acetylcholine molecules are gathered into synaptic vesicles, small membranes with which the neuron can expel. When the neuron 'fires' it releases these molecules into the synaptic cleft, where they can trigger the next neuron by attaching to specific receptors. Acetylcholine is a particularly versatile neurotransmitter and can elicit different effects from different types of neurons.

The cholinergic system includes the neurotransmitter acetylcholine, the receptors to which it binds, and the neurons these receptors affect. The cholinergic system is one of the most important and well-studied systems of neurotransmission. The body relies acetylcholine and the cholinergic system for a variety of functions. Outside the brain, it helps stimulate muscle contraction and regulate heart rate. Within the brain, it plays a role in basic mental processes, such as memory, learning, and feelings of reward. It is also the system affected by nicotine and thus responsible for the potency of cigarette addiction.

Choline acetyltransferase is produced by a gene called CHAT. There are several different versions of the CHAT gene, all of which can successfully produce choline acetyltransferase. Sometimes, however, mutations in this gene result in a failure to effectively produce the intended enzyme. These mutations, along with observed deficiencies of choline acetyltransferase, appear to correlate with both Alzheimer's disease and schizophrenia.

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