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, see below.
This means that small molecule neurotransmitters can be 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 the muscle fiber. In the presynaptic terminal, acetylcholine is synthesized from acetyl coenzyme A 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 VAChT.
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 then 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 enzyme 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 hydroxymethyltransferase 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. 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. Acetylcholine is found in both the central and peripheral nervous systems.
Choline is taken up by the neuron. When the enzyme called choline acetyltransferase is present, choline combines with acetyl coenzyme A CoA to produce acetylcholine. Dopamine, norepinephrine and epinephrine are a group of neurotransmitters called "catecholamines". Norepinephrine is also called "noradrenalin" and epinephrine is also called "adrenalin". Each of these neurotransmitters is produced in a step-by-step fashion by a different enzyme.
Neurotransmitters are made in the cell body of the neuron and then transported down the axon to the axon terminal. Molecules of neurotransmitters are stored in small "packages" called vesicles see the picture on the right. Neurotransmitters are released from the axon terminal when their vesicles "fuse" with the membrane of the axon terminal, spilling the neurotransmitter into the synaptic cleft. Unlike other neurotransmitters, nitric oxide NO is not stored in synaptic vesicles.
Rather, NO is released soon after it is produced and diffuses out of the neuron. NO then enters another cell where it activates enzymes for the production of "second messengers.
Neurotransmitters will bind only to specific receptors on the postsynaptic membrane that recognize them. Neurotransmitters and Neuroactive Peptides Communication of information between neurons is accomplished by movement of chemicals across a small gap called the synapse.
Discovery of Neurotransmitters In , an Austrian scientist named Otto Loewi discovered the first neurotransmitter. Otto Loewi's Experiment Neurotransmitter Criteria Neuroscientists have set up a few guidelines or criteria to prove that a chemical is really a neurotransmitter.
The chemical must be produced within a neuron. The chemical must be found within a neuron. When a neuron is stimulated depolarized , a neuron must release the chemical. When a chemical is released, it must act on a post-synaptic receptor and cause a biological effect. After a chemical is released, it must be inactivated. Inactivation can be through a reuptake mechanism or by an enzyme that stops the action of the chemical. If the chemical is applied on the post-synaptic membrane, it should have the same effect as when it is released by a neuron.
Neurotransmitter Types There are many types of chemicals that act as neurotransmitter substances. Transport and Release of Neurotransmitters Neurotransmitters are made in the cell body of the neuron and then transported down the axon to the axon terminal. Inactivation of Neurotransmitters The action of neurotransmitters can be stopped by four different mechanisms: 1.
Diffusion: the neurotransmitter drifts away, out of the synaptic cleft where it can no longer act on a receptor. Diffusion 2. Enzymatic degradation deactivation : a specific enzyme changes the structure of the neurotransmitter so it is not recognized by the receptor. For example, acetylcholinesterase is the enzyme that breaks acetylcholine into choline and acetate. Enzymatic degradation 3. Glial cells: astrocytes remove neurotransmitters from the synaptic cleft. Glial Cells Astrocyte Image courtesy of Biodidac 4.
Reuptake: the whole neurotransmitter molecule is taken back into the axon terminal that released it.
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