Chapter 6 Neurotransmitter Systems Flashcards
Cholinergic Neurons
Acetylcholine (ACh) is the neurotransmitter at the neuromuscular
junction and is therefore synthesized by all the motor neurons in the
spinal cord and brain stem. Requires ChAT (what are only in cholinergic neurons, good marker)
-memory, arousal, analgesia (kiputunnottomuus)
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Synthesis and degradation of ACh
synthesis: Acetyl CoA + Choline
Degradation : By AchE -> Acetic acid + Choline (in the cleft).
The lilfe cycle of ACh
ACh released-> Choline and acetic acid produced-> Cholines influx to the cell via a transporter that requires Na+ to power to movement. ->choline limits how much ACh is synthesized (transport of choline to neuron is said to be rate-limiting step in ACh synthesis)-> ACh synthesized by Acetyl CoA and choline and up to vesicles by ACh transporter.
What else do cholinergic neurons manufacture?
ACh degradative enzyme acetylcholinesterase (AChE). AChE degrades ACh into choline and acetic acid. ->Inhibition of AChE prevents the breakdown of ACh.
Catecholaminergic Neurons
Three different amine neurotransmitters are collectively called catehcholamines.
-dopamine (DA) , norepinephrine (NE), and epinephrine, also called adrenaline
-Found in nervous system involved in the regulation of movement, mood, attention, and visceral function
Catecholaminergic neurons all contain? What are the steps of catecholamines synthesis?
They all contain the ezyme tyrosine hydroxylase (TH) which catalyzes -> conversion of tyrosine to dopa.
- > Dopa is converted into the neurotransmitter DA by the enzyme dopa decarboxylase(the amount of DA synthesized depends primarily on the amount of dopa available. )
- > Neurons that use NE as a neurotransmitter contain, in addition to TH and dopa decarboxylase, the enzyme dopamine -hydroxylase (DBH) , which converts DA to NE. ( DBH is not found in the cytosol but instead is located within the synaptic vesicles.-> DA made into NE in vesicles)
- > The last in the line of catecholamine neurotransmitters is epinephrine (adrenaline). Adrenergic neurons contain the enzyme phentolamine N -methyltransferase (PNMT), which converts NE to epinephrine. (made in cytosol->back to vesicle to be relesed)
How are catcholamines recycled or degraded?
he catecholamine systems have no fast extracellular degradative enzyme. Instead, the actions of catecholamines in the synaptic cleft are terminated by selective uptake of the neurotransmitters back into the axon terminal via Na -dependent transporters.
Once inside the axon terminal, the catecholamines may be reloaded into synaptic vesicles for reuse, or they may be enzymatically destroyed by the action of monoamine oxidase (MAO) , an enzyme found on the outer membrane of mitochondria.
end-product inhibition
Regulation: For example, decreased catecholamine release by the axon terminal causes the catecholamine concentration in the cytosol to rise, thereby inhibiting TH.
Synthesis of serotonin
Tryptophan-> (5-HTP) by the enzyme tryptophan hydroxylase.
- > The 5-HTP is then converted to 5-HT by the enzyme 5-HTP decarboxylase
- Serotonin synthesis appears to be limited by the availability of tryptophan in the extracellular fluid bathing neurons.( The source of brain tryptophan is the blood, and the source of blood tryptophan is the diet (grains, meat, dairy products, and chocolate are particularly rich in tryptophan). )
How is serotonin (5-HT) removed from synaptoc cleft?
by the action of a specific transporter.
->Once it is back in the cytosol of the serotonergic axon terminal, the transmitter is either reloaded into synaptic vesicles or degraded by MAO.
Glutamate and glycine synthesis?
from glucose and other precursors by the action of enzymes that exist in all cells.
GABA synthesis?
not one of the 20 amino acids used to construct proteins, it is synthesized in large quantities only by the neurons that use it as a neurotransmitter.
->The precursor for GABA is glutamate. Synthesised by GAD.
How are to synaptic actions of the amino acid neurotransmitters terminated?
By selective uptake into the presynaptic terminals and glia, once again via specific Na -dependent transporters. Inside the terminal or glial cell, GABA is metabolized by the enzyme GABA transaminase .
Structure of receptors, nicotinic ACh receptors, GABA A and glycine, glutamate, ATP:
Nicotinic ACh receptor, GABA A, glycine:
-two alfa subunits, and one each of beta, ypsilon and sigma.=five protein subunits
-four separate segments that will coil into alpha helices
Glutamate: four sub unit
purineric ATP: three subunits
Importance of Ca2+:
trigger presynaptic neurotransmitter release, activate many enzymes, regulate the opening of a variety of channels, and affect gene expression; in excessive amounts, Ca+2 can even trigger the death of a cell