A few criteria must be met for a molecule to be called a neurotransmitter. First, the transmitter must be synthesized within the presynaptic neuron. Second, the transmitter must be released by the presynaptic neuron in response to stimulation. When a postsynaptic neuron is treated with the transmitter by a researcher, the molecule must cause the same effect in the postsynaptic neuron as when it is released by a presynaptic neuron.
There are two main categories of neurotransmitters, small molecule transmitters and peptide transmitters. Synthesis and storage of these neurotransmitter groups differ. Small molecule neurotransmitters Neuropeptides are synthesized in the cell body and must be transported to the terminal, which can lead to slower release. Additionally, a neuron will typically synthesize and release only one type of small molecule neurotransmitter, but can synthesize and release more than one neuropeptide.
The small molecule transmitters can be divided into two main groups, amino acid neurotransmitters and biogenic amines, also called monoamines. In addition to acting as neurotransmitters, The amino acids glutamate and glycine are used to synthesize proteins in all cell types throughout the body. GABA is a metabolite of glutamate, but is not used in protein synthesis in the body. The biogenic amines include serotonin and histamine, and the subgroup the catecholamines, dopamine, norepinephrine, and epinephrine.
Acetylcholine does not fit into either division, but is still considered a small molecule neurotransmitter. Most small molecule neurotransmitters are synthesized by enzymes that are located in the cytoplasm. The exception is norepinephrine, which we will discuss. This means that small molecule neurotransmitters can be synthesized by enzymes that are located in the cytoplasm. synthesized and packaged for storage in the presynaptic terminal using enzymes present in the terminal.
Acetylcholine is best known for its role at the neuromuscular junction, the synapse between a motor neuron and a cell. and the muscle fiber. In the presynaptic terminal, acetylcholine is synthesized from acetyl CoA and choline via the enzyme choline acetyltransferase.
The level of enzyme activity is the rate-limiting step in the synthesis pathway. Acetylcholine is packaged into vesicles for storage in the terminal via the vesicular acetylcholine transporter. Glutamate is an amino acid transmitter and is the primary excitatory neurotransmitter in the brain.
In the presynaptic terminal, glutamine is converted into glutamate via the enzyme glutaminase, which is the rate-limiting step in the synthesis pathway. Glutamate is packaged into vesicles for storage via the vesicular glutamate transporter. Glutamate is used to synthesize GABA, another amino acid transmitter and the primary inhibitory neurotransmitter in the brain. In the presynaptic terminal, glutamate is converted into GABA via the end- glutamic acid decarboxylase, which, like the other synthesis pathways, is the rate-limiting step. GABA is packaged into vesicles for storage in the terminal via the vesicular inhibitory amino acid transporter.
Glycine is another inhibitory amino acid neurotransmitter, but unlike GABA, it is more common in the spinal cord than in the brain. Serine hydroxy methyl transferase converts the amino acid serine into glycine in the presynaptic terminal. The rate-limiting step for glycine synthesis occurs earlier in the pathway prior to serine synthesis. Glycine is packaged into vesicles.
by the vesicular inhibitory amino acid transporter like GABA. Dopamine, a catecholamine transmitter, plays many roles in the nervous system, but it is best known for its roles in reward and movement. In the presynaptic terminal, the amino acid tyrosine is converted into dopa via tyrosine hydroxylase, which is the rate-limiting step in the synthesis of all the catecholamines. Dopa is then converted to dopamine, by dopa-decarboxylase. Dopamine is packaged into synaptic vesicles by the vesicular monoamine transporter.
In neurons that release norepinephrine, which is another catecholamine transmitter, once dopamine is packaged into the synaptic vesicles, a membrane-bound enzyme called dopamine beta-hydroxylase converts dopamine into norepinephrine. Therefore, unlike the other small molecule neurotransmitters, norepinephrine is synthesized within the vesicles, not in the cytoplasm. Like dopamine, the rate-limiting step of this synthesis pathway is the activity of tyrosine hydroxylase. Epinephrine, also called adrenaline, is a catecholamine, but it is often considered a hormone instead of a neurotransmitter. Epinephrine is primarily released by the adrenal medulla into the circulation.
It is used as a neurotransmitter in only a small number of neurons. Epinephrine is synthesized from norepinephrine in the cytoplasm by the enzyme phenylethanolamine N-methyltransferase. So epinephrine synthesis requires norepinephrine to exit the vesicles where it was synthesized.
After synthesis in the cytoplasm, epinephrine is repackaged into vesicles via the vesicular monoamine transporter. Serotonin, a biogenic amine neurotransmitter, is known for its role in mood. Tryptophan is converted into 5-hydroxytryptophan by tryptophan hydroxylase.
This is also the rate-limiting step of the synthesis pathway. Then, aromatic L-amino acid decarboxylase converts the 5-hydroxytryptophan into serotonin. Serotonin is packaged into vesicles by the vesicular monoamine. transporter, similar to the other monoamine neurotransmitters, dopamine and epinephrine.
Finally, histamine is another biogenic amine transmitter that is synthesized from histidine through the action of histidine decarboxylase, the rate-limiting step of the pathway. Like other monoamine neurotransmitters, it is packaged into synaptic vesicles via the vesicular monoamine transporter. Neuropeptides are a short string of amino acids and are known to have a wide range of effects from emotions to pain perception. Unlike small molecule neurotransmitters, neuropeptides are synthesized in the cell body. and transported to the axon terminal.
Like other proteins, neuropeptides are encoded by the genes on the DNA located in the nucleus. Messenger RNA is translated into an amino acid cell sequence for a precursor molecule called a pre-propeptide in the rough endoplasmic reticulum. The pre-propeptide is processed further to the propeptide stage.
The remaining processing and packaging of the final neuropeptide into a vesicle occurs in the Golgi apparatus. The peptides are packaged into vesicles that are significantly larger than the vesicles that store the sperm. small molecule transmitters.
These large vesicles must then move from the soma to the terminal. The packaged peptides need to be transported to the presynaptic terminal to be released into the synaptic cleft. Organelles, vesicles, and proteins can be moved from the cell body to the terminal via entero grade transport, or from the terminal to the cell body via retrograde transport.
Interior grade transport can be either fast or slow. The packaged neuropeptides are transported to the synaptic terminals via fast, anterograde axonal transport mechanisms.