Week 5-NT synthesis pathways Flashcards Preview

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Flashcards in Week 5-NT synthesis pathways Deck (70)
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1

Categories of NTs

1. ACh
2. Biogenic Amines
3. Amino Acids
4. Neuroactive Peptides

2

Types of Biogenic Amines

1. Dopamine (DA)
2. Norepinephrine (NE)
3. Serotonin
4. Histamine

3

Types of Amino Acid NTs

1. GABA
2. Glutamate
3. Glycine

4

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

5

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

6

Dale's law

a mature neuron makes use of the same combination of NT substances in all of its synapses

7

coexistence

the use of more than 1 NT by a neuron

8

Synthesis for all NT (except neuro-active peptides) occurs in

pre-synaptic terminal

9

ACh synthesis pathway

Acetyl CoA (from metabolism) + choline (from diet)
--->free ACh via CAT (choline acetyl transferase)

10

Deactivating mechanism for ACh

AChE: in synapse, next to ACh receptor
-also in pre-synaptic terminal

11

AChE in synapse by receptor

breaks ACh as soon as it unbinds
-leaves choline + acetate
-->Acetate diffuses
-->choline recycled via transmembrane protein

12

AChE in pre-synaptic terminal

breaks up any ACh not bound or in a vesicle

13

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

14

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

15

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

16

4 transmitter transporters

1. one for ACh
2. one for biogenic amines (VMAT)
3. one for glutamate
4. one for GABA

17

Catecholamines

1. DA
2. NE
(similar synthesis pathway)

18

Indoleamines

Serotonin

19

Catecholamine synthesis

Tyrosine
-->L-Dopa via tyrosine hydroxylase
-->free dopamine via dopa decarboxylase
-->DA within vesicle becomes NE via Dopamine Beta hydroxylase

20

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

21

Synthesis of NE

same as DA except neurons that use NE have additional enzyme (Dopamine beta-hydroxylase) to convert DA to NE within vesicle

22

Deactivating mechanism for catecholamines

reuptake
-membrane transporters have high affinity for NT to draw NT back into terminal

23

types of membrane transporters

1. one for glutamate itself
2. others for GABA, glycine, NE, DA, Serotonin, and choline

24

NET

NE membrane transporter

25

DAT

DA membrane transporter

26

SERT

Serotonin membrane transporter

27

membrane transporter similarities

1. both driven by Na+ concentration gradient
2. both co-transport another ion

28

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+

29

2 enzymes needed to break down catecholamines

1. MAO
2. COMT

*both exist on pre AND post synaptic sides
-breakdown FREE NT

30

Reuptake of NT into terminal

NTs must be taken up into vesicles immediately otherwise MAO/COMT will destroy them

*Vesicles dump close to membrane transporters for efficient reuptake