A Step Further 4.1: Pathways for Neurotransmitter Synthesis
Here we provide reference information on the chemical pathways by which the classic neurotransmitters are synthesized. By understanding these pathways, pharmacologists can target drug discoveries toward affecting specific transmitter systems. Furthermore, because enzyme action is crucial for transmitter synthesis, neuroanatomists can use the anatomical distribution of these enzymes to determine which transmitters are used by different brain regions. For example, the enzyme choline acetyltransferase (ChAT) catalyzes the synthesis of acetylcholine (ACh) from its precursor, choline:
The enzyme acetylcholinesterase (AChE) breaks down the ACh, leaving choline and acetic acid:
As it turns out, AChE is very widely distributed, but ChAT is found primarily in the nuclei shown in the cholinergic pathway in Figure 4.4 of the printed text.
All of the catecholamine transmitters (norepinephrine, epinephrine, and dopamine) are synthesized from the amino acid tyrosine, in a succession of metabolic steps:
Note that only neurons that possess the enzyme tyrosine hydroxylase have the capacity to produce any catecholamine transmitter, and that l-dopa is a precursor for all three.
The indoleamine serotonin is produced from the amino acid tryptophan in two chemical steps:
The monoamines (dopamine, norepinephrine, epinephrine, serotonin, and melatonin) are inactivated through a combination of presynaptic reuptake and enzymatic breakdown. Most of this enzymatic action is performed by a class of enzymes called monoamine oxidases (MAOs).
Neuropeptides are synthesized like any other peptide or protein—through transcription of a gene and translation of messenger RNA (mRNA)—so we can find neurons making those transmitters by looking for the appropriate mRNA transcript (see the Appendix).