Flashcards in Week 5-NT synthesis pathways Deck (70)
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Categories of NTs
1. ACh
2. Biogenic Amines
3. Amino Acids
4. Neuroactive Peptides
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Types of Biogenic Amines
1. Dopamine (DA)
2. Norepinephrine (NE)
3. Serotonin
4. Histamine
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Types of Amino Acid NTs
1. GABA
2. Glutamate
3. Glycine
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Types of Neuroactive peptides
1. POMC w/in beta-endorphin group
2. pro-enkephalin w/in met & leu-enkephalins
3. Pro-dynorphin in which group is dynorphin
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4 criteria for NT
1. Must be synthesized in the neuron
2. must be released in sufficient amounts upon an AP to yield PSPs
3. Exogenous (artificial) applications will mimic normal activity
4. there must be some deactivating mechanisms to terminate NT-receptor interactions
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Dale's law
a mature neuron makes use of the same combination of NT substances in all of its synapses
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coexistence
the use of more than 1 NT by a neuron
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Synthesis for all NT (except neuro-active peptides) occurs in
pre-synaptic terminal
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ACh synthesis pathway
Acetyl CoA (from metabolism) + choline (from diet)
--->free ACh via CAT (choline acetyl transferase)
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Deactivating mechanism for ACh
AChE: in synapse, next to ACh receptor
-also in pre-synaptic terminal
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AChE in synapse by receptor
breaks ACh as soon as it unbinds
-leaves choline + acetate
-->Acetate diffuses
-->choline recycled via transmembrane protein
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AChE in pre-synaptic terminal
breaks up any ACh not bound or in a vesicle
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3 critical issues in NT systems
1. vesicles are "safety zone" to protect NT from enzymes
2. vesicles not saturated (not filled to capacity)
3. how do NT molecules get into the vesicle
*filling vesicles important in synaptic plasticity
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Vesicle membrane mechanisms
1. transmitter transporters (uses energy from H+ flowing down gradient outside the cell, in exchange for NT coming into cell)
2. proton pumper-energy source for transmitter transporter (uses ATP to pump H+ against gradient)
vesicle exchanges 2H+/1NT brought in
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Vesicle NT uptake mechanism (Vesicular NT transporter)
1. H+ binds inside-->conformational change-->expose NT binding site
2. NT binds on outside
3. 2nd H+ binds inside-->another conformational change
4. NT released inside vesicle, 2 H+ released into cytoplasm
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4 transmitter transporters
1. one for ACh
2. one for biogenic amines (VMAT)
3. one for glutamate
4. one for GABA
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Catecholamines
1. DA
2. NE
(similar synthesis pathway)
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Indoleamines
Serotonin
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Catecholamine synthesis
Tyrosine
-->L-Dopa via tyrosine hydroxylase
-->free dopamine via dopa decarboxylase
-->DA within vesicle becomes NE via Dopamine Beta hydroxylase
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Tyrosine hydroxylase cofactor mechanism
*must have pteridine cofactor to become active
pteridine H4 cofactor gives 2 H+ to tyrosine hydroxylase
-->becomes pteridine H2 cofactor
-->pteridine reductase adds 2 H+ back to pteridine H2 cofactor
-->back to pteridine H4 cofactor
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Synthesis of NE
same as DA except neurons that use NE have additional enzyme (Dopamine beta-hydroxylase) to convert DA to NE within vesicle
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Deactivating mechanism for catecholamines
reuptake
-membrane transporters have high affinity for NT to draw NT back into terminal
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types of membrane transporters
1. one for glutamate itself
2. others for GABA, glycine, NE, DA, Serotonin, and choline
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NET
NE membrane transporter
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DAT
DA membrane transporter
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SERT
Serotonin membrane transporter
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membrane transporter similarities
1. both driven by Na+ concentration gradient
2. both co-transport another ion
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membrane transporters differences
1. GluT is smaller (span 6-8x)
others are larger (span 12x)
2. GluT cotransports K+ along with Na+
others cotransport Cl- along with Na+
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2 enzymes needed to break down catecholamines
1. MAO
2. COMT
*both exist on pre AND post synaptic sides
-breakdown FREE NT
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