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Lecture

Neurotransmitter Chemistry.docx

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Department
Psychology
Course
PSYC 4750
Professor
Linda Hunter
Semester
Fall

Description
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  End-product inhibition- decreased catecholamine release by the axon terminal causes the catecholamine concentration in the cytosol to rise  Dopa is converted into the neurotransmitter dopamine by the enzyme dopa decarboxylase o Dopa decarboxylase is abundant in catecholaminergic neurons, so the amount of dopamine synthesized primarily depends on the amount of dopa available  Neurons that use norepinephrine (NE) as a neurotransmitter contain, besides TH and dopa decarboxylase, they contain the enzyme do
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