PS271 Lecture Notes - Tryptophan Hydroxylase, Respiratory Failure, Cholinergic

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1 Feb 2013
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Neurotransmitter Chemistry
Most of the known neurotransmitter molecules are either:
o Amino acids
o Amines derived from amino acids
o Peptides constructed from amino acids
ACh is an exception; but it is derived from acetyl CoA,
Choline which is important for fat metabolism throughout the body
Amino acid and amine transmitters are generally each stored in and released by separate sets of neurons
Dale’s principle- idea that a neuron has only one neurotransmitter
Many peptide containing neurons violate Dale’s principle because these cells usually release more than one
neurotransmitter: an amino acid or amine and a peptide
Co-transmitters- two or more transmitters released from one nerve terminal
But still most neurons release only a single amino acid or amine neurotransmitters
Cholinergic Neurons:
Acetylcholine (ACh)- is the neurotransmitter at the neuromuscular junction and therefore is synthesized by all the
motor neurons in the spinal cord and brain stem
ACh synthesis requires a specific enzyme, choline acetyltransferase (ChAT)
ChAT is manufactured in the soma and transported to the axon terminal like all presynaptic proteins
Only cholinergic neurons contain ChAT, therefore this enzyme is a good marker to identify cells that use ACh as it’s
neurotransmitter
ChAT synthesizes ACh in the cytosol of the axon terminal, and the neurotransmitter is concentrated in synaptic vesicles
by the actions of an ACh transporter
o ChAT transfers an acetyl group from acetyl CoA to choline
o Source of choline is the extracellular fluid, where it exists in low micromolar concentrations
o Choline is taken up by the cholinergic axon terminals via specific transporter
o Because the availability of choline limits how much ACh can be synthesized in the axon terminal, transport of
choline into the neuron is said to be the rate-limiting step in ACh synthesis
Rate-limiting Step- in a biochemical reaction that leads to the production of a chemical, the one step that limits the rate
of synthesis.
Cholinergic neurons also manufacture the ACh degradative enzyme acetylcholinesterase (AChE)
o AChE is secreted into the synaptic cleft and is associated with cholinergic axon terminal membranes
o AChE is also manufactured by some noncholinergic neurons, so this enzyme is not as useful a marker for
cholinergic synapses as ChAT
AChE degrades ACh into choline and acetic acid
o This happens very quickly because AChE has one of the fastest catalytic rates among all known enzymes
Inhibition of AChE prevents the breakdown of ACh, disrupting transmission at cholinergic synapses on skeletal muscle
and heart muscle
o Deaths from the irreversible inhibition of AChE is typically a result of respiratory paralysis
Catecholaminergic Neurons
Amino acid tyrosine is the precursor for three different amine neurotransmitters that contain a chemical structure
called a catechol
These neurotransmitters are called catecholamines
o Catecholamine neurotransmitters are:
Dopamine (DA)
Norepinephrine (NE)
Epinephrine (Adrenaline)
Catecholaminergic neurons are found in regions of the nervous system involved in the regulation of movement, mood,
attention, and visceral function
All catecholaminergic neurons contain the enzyme tyrosine hydroxylase (TH), which catalyzes the first step in
catecholamine synthesis, the conversion of tyrosine to a compound called dopa
Activity of TH is rate limiting for catecholamine synthesis
The enzyme’s activity is regulated by various signals in the cytosol of the axon terminal
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Document Summary

Most of the known neurotransmitter molecules are either: amino acids, amines derived from amino acids, peptides constructed from amino acids. Ach is an exception; but it is derived from acetyl coa, Choline which is important for fat metabolism throughout the body. Amino acid and amine transmitters are generally each stored in and released by separate sets of neurons. Dale"s principle- idea that a neuron has only one neurotransmitter. Many peptide containing neurons violate dale"s principle because these cells usually release more than one neurotransmitter: an amino acid or amine and a peptide. Co-transmitters- two or more transmitters released from one nerve terminal. But still most neurons release only a single amino acid or amine neurotransmitters. Acetylcholine (ach)- is the neurotransmitter at the neuromuscular junction and therefore is synthesized by all the motor neurons in the spinal cord and brain stem. Ach synthesis requires a specific enzyme, choline acetyltransferase (chat)

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