Neurotransmitters sytem 2: Gaba and Glycine

Question 1

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

Answer 1

Inhibitory NT of the cns

Question 2

what is the precursor of GABA?

Answer 2

Glutamate

Question 3

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

Answer 3

Glutamat= excitatory
GABA= inhibitory

Question 4

Describe the process of converting Glutamate into GABA.

Answer 4

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

Question 5

where is GABA synthesised?

Answer 5

at nerve terminals

Question 6

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

Answer 6

Using a vesicular inhibitory amino acid transporter (VIAT)

Question 7

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

Answer 7

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

Question 8

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

Answer 8

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

Question 9

what are 3 methods of termination of GABA?

Answer 9

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

Question 10

Describe the process of re-uptake of GABA

Answer 10

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

Question 11

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

Answer 11

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

Question 12

describe the process of GABA degradation Into succinct acid

Answer 12

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)

Question 13

What are the 2 receptor types?

Answer 13

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

Question 14

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

Answer 14

both metabotropic and ionotropic

Question 15

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

Answer 15

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

Question 16

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

Answer 16

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)

Question 17

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

Answer 17

To the alpha interface of the alpha between alpha and beta

Question 18

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

Answer 18

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

Question 19

what subunits make up the GABAA receptor?

Answer 19

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)

Question 20

what type of modulator is Benzodiazepine?

Answer 20

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

Question 21

Describe GABAB receptors

Answer 21

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

Question 22

When GABA binds to GABAB receptor what mechanism occurs?

Answer 22

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

Question 23

what kind of drug is benzodiazepine

Answer 23

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

Question 24

What condition is GABA associated with?

Answer 24

epilepsy

Question 25

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

Answer 25

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

Question 26

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

Answer 26

conversion of GABA to glutamate In the brain

Question 27

what is epilepsy?

Answer 27

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

Question 28

what is anxiety?

Answer 28

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

Question 29

what is the relationship between GABA and anxiety.

Answer 29

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

Question 30

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

Answer 30

Anxiolytics e.g benzodiazepine

Question 31

what type of NT is Glycine?

Answer 31

Inhibitor of the CNS

Question 32

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

Answer 32

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

Question 33

Where is Glycine made?

Answer 33

Nerve terminal

Question 34

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

Answer 34

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

Question 35

what type of receptor is there for Glycine?

Answer 35

LGICR

Question 36

Describe the structure of Glycine receptor

Answer 36

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

Question 37

Alkaloid strychnine does what to the glycine receptor?

Answer 37

blocks the ion channel

Question 38

what terminates Glycine?

Answer 38

re-uptake into the pre-synaptic neuron

Question 39

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

Answer 39

Sodium dependent Glycine re-uptake transporter (GlyT)

Question 40

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

Answer 40

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

Question 41

describe the process of degradation of Glycine

Answer 41

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

Question 42

what is hyperekplexia?

Answer 42

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

Question 43

what is the relationship between hyperekplexia and glycine?

Answer 43

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