Neurotransmitters sytem 2: Gaba and Glycine Flashcards
what type of neurotransmitter is Gamma-aminobutyric acid (GABA)?
Inhibitory NT of the cns
what is the precursor of GABA?
Glutamate
what type of NT is glutamate and what kind of NT is GABA ?
Glutamat= excitatory
GABA= inhibitory
Describe the process of converting Glutamate into GABA.
Glutamate conversion to GABA requires the enzyme: Glutamate decarboxylase (GAD) and the use of a co-factor:Pyridoxal phosphate (derived from vitamin b6)
where is GABA synthesised?
at nerve terminals
After glutamate is converted into GABA how are they transported into the vesicles?
Using a vesicular inhibitory amino acid transporter (VIAT)
How can you differentiate between the Glycine/GABA vesicles compared to the glutamate vesicles?
1)GABA/Glycine vesicles are oval in shape
2)Glutamate=round in shape
why is there a difference in the shapes of the vesicles that contain GABA/Glycine to those that contain Glutamate?
Due to electrostatic interactions in the vesicles being different, resulting in different shapes.
what are 3 methods of termination of GABA?
1)For it to diffuse across the synapse
2)GABA re-uptake transporter
3) GABA transaminase which breaks down GABA
Describe the process of re-uptake of GABA
1)GABA re-uptaken into the pre-synaptic neuron via GAT, GABA re-uptake transporters from the synaptic cleft
are there any isoforms of GAT? name 2 examples and where they are located
1)Yes
2)GAT-1 = Neurons
3)GAT-3= Glial cells
describe the process of GABA degradation Into succinct acid
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)
What are the 2 receptor types?
1)Ionotropic= ligand gated ion channels
2)Metabotropic= GPCR
On what types/types of receptor does GABA bind to?
both metabotropic and ionotropic
what are the names of the ionotropic and metabotropic receptors that GABA binds to?
1)Ionotropic=GABAA receptor
2)Metabotropic= GABAB receptor
Describe the GABAA receptor and what affect there is after binding of GABA to it.
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)
at which subunit does GABA bind to on GABAA receptor for the ion channel to open?
To the alpha interface of the alpha between alpha and beta
What is Benzodiazepine?where does it bind on the GABAA receptor?what affect does this have?
1)Agnoist that enhances the influx of Cl- through the ion Chanel, resulting in greater inhibition
2)Between the alpha and gammasubunits
what subunits make up the GABAA receptor?
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)
what type of modulator is Benzodiazepine?
Allosteric modulator- as it binds to the allosteric binding site on GABAA receptor
Describe GABAB receptors
1)metabotropic receptor= GPCR
2)structure=extracellular venus flytrap domain, internal c doman and this interacts with the G proteins, Gi protein.
When GABA binds to GABAB receptor what mechanism occurs?
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
what kind of drug is benzodiazepine
depressants that produce sedation and hypnosis, relieve anxiety and muscle spasms, and reduce seizures (anti-epileptic)
What condition is GABA associated with?
epilepsy
The cerebrum controls fine movement and balance. It contains purkinje cells. what type of neurons are these?
purkinje cells are are a class of GABAergic neurons that comprise the principle projection neurons of the cerebellar cortex.
in the brain GABA and Glutamate work together and need to be balanced. How do they change from inhibition to excitation?
conversion of GABA to glutamate In the brain
what is epilepsy?
Epilepsy is a brain disorder characterised by periodic and unpredictable seizures mediated by the rhythmic firing of large groups of neurons
what is anxiety?
Anxiety can be defined as a feeling of unease (e.g. worry or fear), which can range from mild to severe
what is the relationship between GABA and anxiety.
1)GABA can lessen anxiety and result in a calming effect
what is the name of the drugs that bind to GABA receptors to lessen anxiety?
Anxiolytics e.g benzodiazepine
what type of NT is Glycine?
Inhibitor of the CNS
Describe the process of synthesis of Glycine (hint start from 3-phosphoglycerate from glycolysis) Name both the enzyme and co-factor involved.
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
Where is Glycine made?
Nerve terminal
Once Glycine has been made at the nerve terminals it gets transported into vesicles with the help of what?
Transported into vesicles by vesicular
inhibitory amino acid transporters
(VIAAT)
what type of receptor is there for Glycine?
LGICR
Describe the structure of Glycine receptor
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
Alkaloid strychnine does what to the glycine receptor?
blocks the ion channel
what terminates Glycine?
re-uptake into the pre-synaptic neuron
What transporter is used for the re-uptake of glycine into the pre-synaptic neuron?
Sodium dependent Glycine re-uptake transporter (GlyT)
what are the names of the Glycine re-uptake transporters found in neurons and in glial cells?
1)Neurons= GlyT-1
2)Glial cells=GlyT-2
describe the process of degradation of Glycine
Glycine is converted into serine via the enzyme =hydroxy-methyl transferase
what is hyperekplexia?
Hyperekplexia is a rare disorder characterised by hypertonia (increased muscle tone) and an exaggerated startle response.
what is the relationship between hyperekplexia and glycine?
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
