Amino acids transmitters Flashcards
(31 cards)
What are the different amino acid transmitter families?
Excitatory-glutamate, aspartate, N-acetylasparytyl glutamate, glycine.
Inhibitory- GABA, glycine- taurine/beta alanine.
When were GABA, glycine and glutamate discovered?
19050-1970’s
11970-1980’s
1980’s
Explain amino acid metabolism? What do they feed into?
Glutamate can be synthesises into:
- GABA-T via GAD
-glutamine via glutamine synthase and reverse back to glutamate via glutaminase.
-glutamate to alpha-ketoglutarate that enters the Krebs cycle and also can become aspartate and glycine through transaminase.
Explain the glutamine cycle (excitatory amino acid)?
- VGluT- metabolise glu so it can be transported.
- Glutaminase- gin into glu
- Glutamine synthetase- broken down in astrocytes so it can be recycled and reused.
What are the two types of glutamate recptor?
Ionotropic and Metabotropic.
Ionotropic glutamate receptors?
LG ion channles, fast, iglu, includes: AMPA, Kiante, NMDA. E.g. nAChR.
The iGluR subunits have 3 transmembrane domains and are tetramers with 4 agonist binding sites.
Explain Inotropic receptor sub unit combinations for NMDA, AMPA, Kainate.
NMDA:
glu N1/N2A/ 3A-B
AMPA:
GluA 1-4
Kainate:
GluK1-3
there heterotrimers
make up a variety if different r’s
splicing can increase this diversity.
Metabotropic glutamate receptors?
Family c of GPCR
slower
mGluR
3 groups
1-mGluR 1,5
2-mGluR 2,3
3- mGluR 4,6,7,8
Which amino acid is inhibitory?
GABA gamma-aminobutyric acid
Key feature about GABA gamma-aminobutyric acid?
wide distribution in the CNS.
stored in vesicles and release when there’s influx of ca and high ca conc.
there’s transporter proteins for uptake and add to vesicular pool.
formed from glutamate by glutamic acid decarboxylase.
There’s GABA-A and GABA-B AND GABA-C families
What happens at the GABAergic terminal?
Gaba released from vesicles diffuse across the synapse to r on the post, GAT1 recycles and reuses it for use again.
Explain GABAergic transmission?
20% all neurons are GABA
20% of all CNS transmitters
short local connections
some long projections to the striatum to the substantia nigra and globus pallidus.
also in brain tissue and synapses.
What happens when the GABA receptor is activated?
GABA binds to the GABAA receptor, it opens a cl- channel allow cl- influx into the cell. So the cell increases in chloride permeability (Pcl). Ecl is close to resting membrane potential so influx stabilises membrane potential so stays near rest and leads to inhibition.
What are the different type of GABA rectors and how many types are in each?
6x Benzodiazepine, beta-carboline site
1x Typical GABA A site
5x Neurosteroid sites
4x Barbiturate, propofol, etomidate site
3x picrotoxinin site
2x agonist binding sites
What compounds enhance and decrease GABA A fucniton?
enhance- sedatives, anxiolytics, anticonvulsants.
decrease- convulsant, anxiogenics.
What GABA A Receptor subunit genes are there ? and how many? Which are most common?
alpha 1-6
beta 1-3
gamma 1-3
delta
epsilon
pi
Theta
rho 1-3 (retinal expression for GABA C.
most common are a,b,y.
Where are the binding sites located in relation to the subunits?
between a1 and b2, b2,a1, a1,y2. in the interfaces. There’s also a benzodiazepine site that has high affinity but it needs a y2 subunit.
Key features of extra synaptic GABAA receptors?
outside the synapses
high affinity
respond to ambient gaba to produce tonic inhibition
contain delta
insensitive to benzodiazepine
targets for alcohol, Neurosteroid and some anaesthesia
involve din brain disorders
GABA B structure ?
pre or post
two subunits 1/2
GPCR family C
have VG ca channels, , open k channels and inhibit adenylyl cyclase via Gl.
What is a main inhibitory amino acid and its fucntion?
Glycine- High conc in spinal cord
acts diff on a glyR( cys-loop r) compared to NMDA r
transport proteins for reuptake. Glyt1(astrocytes)/2(sc).
get from diet and serine synthesis.
Explain the glycine receptor structure?
3 alpha ( sc, brain, brain), 1 beta.one is for gly and is between the a and b or 2 a.
What are renshaw cells?
SC interneurons, stimulated by collateral from a motor n.
release gly to motor n
neg fdbk
reg MN
antagonist (strychnine)
agonist( gly, taurine, b-alanine)
ethanol anaesthetics modulator
treat pain, epilepsy, hyperekplexia, alcoholism.
Structure of iGluR’s
Sub unit combos for NMDA: N1/2 A-D/ 3 A-B
AMPA: A 1-4
Kainate: K 1-3
4-5
AMPA receptors
mediate fast syn transmission
fast EPSP, wide spread in CNS, rel perm to na, k, ca dep on sub unit
4 subunits bind glutamate,
