Neurotransmitters sytem 2: Gaba and Glycine Flashcards

1
Q

what type of neurotransmitter is Gamma-aminobutyric acid (GABA)?

A

Inhibitory NT of the cns

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2
Q

what is the precursor of GABA?

A

Glutamate

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3
Q

what type of NT is glutamate and what kind of NT is GABA ?

A

Glutamat= excitatory
GABA= inhibitory

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4
Q

Describe the process of converting Glutamate into GABA.

A

Glutamate conversion to GABA requires the enzyme: Glutamate decarboxylase (GAD) and the use of a co-factor:Pyridoxal phosphate (derived from vitamin b6)

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5
Q

where is GABA synthesised?

A

at nerve terminals

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6
Q

After glutamate is converted into GABA how are they transported into the vesicles?

A

Using a vesicular inhibitory amino acid transporter (VIAT)

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7
Q

How can you differentiate between the Glycine/GABA vesicles compared to the glutamate vesicles?

A

1)GABA/Glycine vesicles are oval in shape
2)Glutamate=round in shape

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8
Q

why is there a difference in the shapes of the vesicles that contain GABA/Glycine to those that contain Glutamate?

A

Due to electrostatic interactions in the vesicles being different, resulting in different shapes.

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9
Q

what are 3 methods of termination of GABA?

A

1)For it to diffuse across the synapse
2)GABA re-uptake transporter
3) GABA transaminase which breaks down GABA

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10
Q

Describe the process of re-uptake of GABA

A

1)GABA re-uptaken into the pre-synaptic neuron via GAT, GABA re-uptake transporters from the synaptic cleft

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11
Q

are there any isoforms of GAT? name 2 examples and where they are located

A

1)Yes
2)GAT-1 = Neurons
3)GAT-3= Glial cells

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12
Q

describe the process of GABA degradation Into succinct acid

A

1)GABA converted into Succinic semialdehyde, catalysed by the enzyme = GABA transaminase (GABA-T)
2)Succinic semialdehyde converted into succinic acid, catalysed by the enzyme= Succinic Semialdehyde dehydrogenase (SSADH)

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13
Q

What are the 2 receptor types?

A

1)Ionotropic= ligand gated ion channels
2)Metabotropic= GPCR

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14
Q

On what types/types of receptor does GABA bind to?

A

both metabotropic and ionotropic

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15
Q

what are the names of the ionotropic and metabotropic receptors that GABA binds to?

A

1)Ionotropic=GABAA receptor
2)Metabotropic= GABAB receptor

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16
Q

Describe the GABAA receptor and what affect there is after binding of GABA to it.

A

1)It is a ligand-gated Cl- ion channel
2)Once GABA binds= influx of Cl-
3)Influx of Cl- results in hyperpolarisation as membrane potential drops
4)Has a pemtameric structure (made of 5 subunits)

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17
Q

at which subunit does GABA bind to on GABAA receptor for the ion channel to open?

A

To the alpha interface of the alpha between alpha and beta

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18
Q

What is Benzodiazepine?where does it bind on the GABAA receptor?what affect does this have?

A

1)Agnoist that enhances the influx of Cl- through the ion Chanel, resulting in greater inhibition
2)Between the alpha and gammasubunits

19
Q

what subunits make up the GABAA receptor?

A

1)2x alpha subunits (can be any from alpha 1-6)
2)2x beta subunits (beta 1-3)
3)one gamma subunit (gamma 1-3)

20
Q

what type of modulator is Benzodiazepine?

A

Allosteric modulator- as it binds to the allosteric binding site on GABAA receptor

21
Q

Describe GABAB receptors

A

1)metabotropic receptor= GPCR
2)structure=extracellular venus flytrap domain, internal c doman and this interacts with the G proteins, Gi protein.

22
Q

When GABA binds to GABAB receptor what mechanism occurs?

A

1)GABAB receptors form dimmers with each other due to the c domain linking
2)GABA binds to GPCR
3)Activation of G protein (Gi/o)
4) activation results in K+ channels open on membrane of neuron, resulting in efflux of k+, decreasing the membrane potential
4)Hyperpolarisation
5) The Gi activation also results in the blocking of calcium channels so no Ca2+ can enter= enhanced lvl of positive charge leaving the cell

23
Q

what kind of drug is benzodiazepine

A

depressants that produce sedation and hypnosis, relieve anxiety and muscle spasms, and reduce seizures (anti-epileptic)

24
Q

What condition is GABA associated with?

A

epilepsy

25
Q

The cerebrum controls fine movement and balance. It contains purkinje cells. what type of neurons are these?

A

purkinje cells are are a class of GABAergic neurons that comprise the principle projection neurons of the cerebellar cortex.

26
Q

in the brain GABA and Glutamate work together and need to be balanced. How do they change from inhibition to excitation?

A

conversion of GABA to glutamate In the brain

27
Q

what is epilepsy?

A

Epilepsy is a brain disorder characterised by periodic and unpredictable seizures mediated by the rhythmic firing of large groups of neurons

28
Q

what is anxiety?

A

Anxiety can be defined as a feeling of unease (e.g. worry or fear), which can range from mild to severe

29
Q

what is the relationship between GABA and anxiety.

A

1)GABA can lessen anxiety and result in a calming effect

30
Q

what is the name of the drugs that bind to GABA receptors to lessen anxiety?

A

Anxiolytics e.g benzodiazepine

31
Q

what type of NT is Glycine?

A

Inhibitor of the CNS

32
Q

Describe the process of synthesis of Glycine (hint start from 3-phosphoglycerate from glycolysis) Name both the enzyme and co-factor involved.

A

1) 3-phosphoglycerate made in glycolysis
2)this is then converted into Serine
3)Serine gets converted into Glycine, catalysed by the enzyme= Serine hydroxymethyl transferase with the help of the co-factor = Glutamate dehydroxylase

33
Q

Where is Glycine made?

A

Nerve terminal

34
Q

Once Glycine has been made at the nerve terminals it gets transported into vesicles with the help of what?

A

Transported into vesicles by vesicular
inhibitory amino acid transporters
(VIAAT)

35
Q

what type of receptor is there for Glycine?

A

LGICR

36
Q

Describe the structure of Glycine receptor

A

1) Ligand gated Cl- ion channel
2)pentameric structure- made of 5 subunits= 3 Alpha subunits and 2 beta subunits or 4 alpha subunits and 1 beta subunit
The alpha can be any variant from alpha 1-4

37
Q

Alkaloid strychnine does what to the glycine receptor?

A

blocks the ion channel

38
Q

what terminates Glycine?

A

re-uptake into the pre-synaptic neuron

39
Q

What transporter is used for the re-uptake of glycine into the pre-synaptic neuron?

A

Sodium dependent Glycine re-uptake transporter (GlyT)

40
Q

what are the names of the Glycine re-uptake transporters found in neurons and in glial cells?

A

1)Neurons= GlyT-1
2)Glial cells=GlyT-2

41
Q

describe the process of degradation of Glycine

A

Glycine is converted into serine via the enzyme =hydroxy-methyl transferase

42
Q

what is hyperekplexia?

A

Hyperekplexia is a rare disorder characterised by hypertonia (increased muscle tone) and an exaggerated startle response.

43
Q

what is the relationship between hyperekplexia and glycine?

A

1)Gene mutations (e.g. glycine receptors, glycine
transporters) can disrupt normal glycinergic
neurotransmission
2)Can lead to neuronal hyperexcitability (by impairing
glycinergic inhibition)
3)Leads to hypertonia and exaggerated startle
response

44
Q
A