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I understand that with large neurotransmitters, like neuropeptides, the precursor neurotransmitter and the enzymes are produced in the soma and quickly travel down the axon to be modified in the axon terminal.

With the small molecule transmitters, the enzymes are made in the soma and then transported slowly down the terminal to the terminal where they synthesize the small transmitters.

Why is it that the precursors and enzymes for large neurotransmitters travel fast down the axon, whereas the enzymes for the small transmitters travel slowly? Is there a specific reason?

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  • $\begingroup$ is their a molecular weight for "small" and "large" transmitters that you can reference? Can you add a general reference that talks about this question? $\endgroup$ Jan 19, 2017 at 18:18
  • $\begingroup$ @VanceLAlbaugh I edited the question a big to what I assume the OP was getting at, and already included some clarification in my answer. Textbooks often distinguish two major categories of neurotransmitters: small molecules vs. peptides. $\endgroup$
    – Bryan Krause
    Jan 19, 2017 at 18:22

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I presume you are referring to fast versus slow axoplasmic transport.

I presume by "small neurotransmitters," you are referring to "small molecule" neurotransmitters like GABA, glutamate, acetylcholine, and the catecholamines like dopamine.

For the "large" neurotransmitters, I assume you are referring to peptides.

(for a quick reference on these two categories you can see this book blurb)

Although local protein synthesis is possible outside the soma, particularly in dendrites, and there is even evidence for protein synthesis in axons, including neurotransmitter peptides, most protein synthesis still seems to occur in the vicinity of the nucleus, at the soma. Synthesis anywhere else means you need to transport the mRNAs and translation machinery instead, since the mRNA needs to be made at the nucleus. Even the "large" neurotransmitters, which are peptides, need to be synthesized just like bigger proteins.

Back to axoplasmic transport... There are two main mechanisms for moving things down the axon. The faster version of this transport is really for the transport of vesicles. To transport a neurotransmitter peptide in this fashion, you fill a vesicle full of the peptide and send it on its way along the microtubules via kinesin and dynein motors.

Larger, non-membrane bound proteins, however, are often not transported in vesicles, but by the slower transport mechanism. Note that this transport is still pretty fast, way faster than simple diffusion, it just isn't as fast as the "fast" transport. The exact mechanisms of slow transport are still an active area of research and not fully understood.

To get back to your question, "is there a specific reason?" The reason isn't so much about the speed, but about the mechanism of transport. Small peptides and membrane-bound proteins move in vesicles via fast transport. Large proteins not bound in membranes move via slow transport. The enzymes that synthesize the small neurotransmitters fall into this latter category. Importantly, although the neurotransmitters may be small, the enzymes themselves can be big, at least certainly bigger than the small peptides that are equivalent to the "large" neurotransmitters.

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  • $\begingroup$ Absolutely fantastic answer. Thank you so much for this! Thanks to the links as well haha, I understand everything about the answer I was looking for. Thanks again. $\endgroup$ Jan 20, 2017 at 0:30

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