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Neurobiology > Inhibitory Amino Acid Neurotransmitters > Flashcards

Inhibitory Amino Acid Neurotransmitters Flashcards

0
Q

How is GABA synthesised ?

A

Made from glutamate

Glutamate is converted to GABA by glutamate decarboxylase (GAD) - gad is inhibited by allylglycine

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1
Q

What are examples of inhibitory amino acid neurotransmitters ?

A

GABA - main inhibitory one in the brain
Glycine - main inhibitory one in the spinal cord
Non-essential amino acids

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2
Q

How is GABA broken down ?

A

GABA is broken down to succinic semialdehyde by GABA aminotransferase (GABA-T) - this process requires the conversion of alpha-ketoglutarate to glutamate
GABA-T is mainly in mitochondria

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3
Q

What inhibits GABA-T ?

A

Aminooxyacetic acid and vigabatrin

- these inhibit the breakdown of GABA

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4
Q

What happens to the succinic semialdehyde ?

A

It’s broken down to succinate by succinic semialdehyde dehydrogenase
Succinate can be used as an intermediate in the Krebs cycle to produce GABA or glutamate

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5
Q

What is vigabatrin used to treat ?

A

Used to treat epilepsy because it reduces the breakdown of GABA so increases the amount of GABA

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6
Q

What 2 substances can make GABA ?

A

Glutamate or succinate

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7
Q

What are the GABA receptors ?

A

GABAa - ionotropic - Cl-
GABAb - GPCR - 7 transmembrane domain
GABAc - ionotropic - Cl- - mainly in retinas

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8
Q

What effect does GABA binding to GABAa receptors in adult cells ?

A

Hyperpolarisation because it causes an influx of Cl-

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9
Q

What are the subunits of a GABA receptor like ?

A

Each subunit is 50-60kDa and there overall molecular weight of the receptor is 275kDa so it has 5 subunits
6 classes of subunits: alpha, beta, gamma, epsilon, delta and roe
At least 19 different polypeptide subunits so there is a lot of diversity of GABA receptors

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10
Q

What is the subunit diversity like in GABAa receptors ?

A

Subunits within each group have 70% similarity and the subunits between different groups have 30% similarity

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11
Q

What loop binds GABA and what domain makes the pore ?

A

Cys loop and domain 2 is thought to make the pore lining

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12
Q

What are the 5 distinct binding sites on a GABAa receptor ?

A 
GABA site 
Benzodiazepine site 
Steroid site - anaesthetics
Barbiturate site - depressants 
Picrotoxin site -convulsants
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13
Q

What happens when benzodiazepines bind to GABAa receptors ?

A

It enhances the effects of GABA binding

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14
Q

What happens when picrotoxin binds to GABAa receptors ?

A

The binding site is within the pore of the channel and it blocks the receptor preventing its inhibitory activity

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15
Q

What effects occur when GABAb is stimulated ?

A

Inhibits adenyl Cyclase
Stimulates phospholipase a2
Activates some potassium channels - voltage gated ones
Inhibits calcium channels on presynaptic nerve terminal preventing further neurotransmitter release
Causes long slow inhibition

16
Q

What are agonists at GABAb receptors ?

A

Baclofen and saclofen

- muscle relaxant and antispastic agent

17
Q

What are antagonists for GABAb receptors ?

A

Phacolfen and 2-hydroxysaclofen

18
Q

Where are glycine receptors located ?

A 
Grey matter of spinal cord 
Medulla 
Midbrain 
Hypothalamus 
Thalamus
19
Q

How is glycine synthesised ?

A

Serine converted to glycine by serine hydroxymethyltransferase

20
Q

How is glycine taken up from the synaptic cleft ?

A

By sodium dependent transporters - GLYT 1 and GLYT 2

21
Q

How is glycine packaged into vesicles ?

A

Can’t find a specific tranpsorter for glycine so it is though that it uses GABA transporter

22
Q

From rat spinal cord what is the structure of glycine receptors like ?

A

Strychnine binding site inhibits the glycine receptor
3 proteins- alpha subunit - 48kDa, beta subunit- 58kDa and gephyrin- 93kDa
There are 3 isoforms of alpha subunit - 1, 2, and 3

23
Q

What is the structure of the glycine receptor like ?

A 
4 transmembrane domains
Part of ligand gated superfamily 
Large n terminal extracellular loop
Larger intracellular loop m3-m4 
Pentamer - adult = 3 alpha and 2 beta while fetal are alpha-2 homomers
24
Q

What is the purpose of gephyrin in the glycine receptor ?

A

Involved in anchoring the receptor to a specific place in the cell

25
Q

What is the glycine receptor involved in ?

A

Reflex response

Causes reciprocal inhibition - voluntary muscle control and sensory processing

26
Q

What happens in hyperperplexia ?

A

It’s an exaggerated reflex
Often caused by a mutation in the glycine receptor
Patients suffering from this will go into a complete state of shock for several minutes upon a shocking stimuli occurring

27
Q

What is hyperperplexia treated with ?

A

Benzodiazepine

28
Q

What increases glycine release ?

A

Tetanus toxin

Neurobiology (30 decks)

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