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EAA
Excitatory Amino Acids
28
Pharmacology
Undergraduate 2
01/17/2017

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Term
What is the main excitatory amino acid neurotransmitter?
Definition
Glutamate
- estimated that over half of brain synapses release glutamate
Term
Which amino acids act as neurotransmitters
Definition
Excitatory:
Glutamate
Aspartate

Inhibitory:
GABA (g-amino butyric acid)
Glycine
Term
What is the difference between Glutamate and Aspartate?
Definition
Aspartate has one less methyl group
Term
Glutamate and aspartate are non-essential amino acids. What does that mean?
Definition
non-essential = Synthesised in the body – not required in the diet
Term
WHat is the relative abundance of Glutamate in the brain?
Definition
186 mg/100g tissue
Term
What is the relative abundance of Aspartate in the Brain?
Definition
114 mg/100g tissue
Term
What is the first pathway synthesis of Glutamate?
Definition
Glycolysis – oxidative metabolism of glucose
Glucose --> pyruvate --> Acetyl CoA --> Krebs cycle --> α-ketoglutarate -->glutamate
Term
What is the second pathway synthesis of Glutamate?
Definition
glutamine --> glutamate
Term
Which enzyme catalyses this reaction :
glutamine --> glutamate ?
Definition
Glutaminase
Term
Which pathway is prefered for release of glutamate?
Definition
Pathway 2 using enzyme Glutaminase
Term
How does glutaminase prevent glutamate overproduction?
Definition
This enzyme is subject to product inhibition
Term
Can glutamate cross the BBB?
Definition
No, therefore it is synthesized using local precursors in the neurons
Term
The glutamine cycle in neurons
Definition
Glutamine --> glutamate
using enzyme = Glutaminase
Term
The glutamine cycle in astrocytes
Definition
Glutamate ---> Glutamine
using enzyme = Glutamine synthase
Term
Reversal of transaminase reaction
Definition
glutamate --> α-ketoglutarate
Term
Glutamate dehydrogenase
Definition
glutamate --> α-ketoglutarate
Term
How is glutamine taken up into presynaptic terminal ?
Definition
Through System A transporter 2 (SAT2)
Term
Where is Glutamate synthesized?
Definition
presynaptic cytoplasm
Term
Where is glutamate stored?
Definition
In vesicles at the terminal
Term
How is glutamate packaged into vesicles?
Definition
Through Vesicular Glutamate transporter (VGLUT) and use the proton antiporter system
Term
VGLUT are highly specific for ... but have low affinity of ....
Definition
L-glutamate
1-2mM Km
Term
There are 3 genes identified with three different types of VGLUT. What are the 3 types?
Definition
neuronal, cerebellar, astrocytic
Term
Which disorder shows abnormality in Glutamate transporter ?
Definition
amyotrophic lateral sclerosis (ALS)
Term
How many transmembrane proteins are there in Glutamate transporters?
Definition
6 - 10 transmembrane proteins
Term
Which transporter removes Glutamate from the synaptic cleft?
Definition
Excitatory Amino Acid transporter (EAAT) family of 5 Na dependent glutamate co-transporters
Term
Distribution of subtypes of EAAT
Definition
EAAT1 (GLAST) – neurons and astroglia, particularly Bergmann glia, cortex, hippocampus and cerebellum
EAAT2 (GLT1) – astroglia
EAAT3 (EAAC1) – neurons
EAAT4 – cerebellar Purkinje cells in rat and human CNS
EAAT5 – primarily expressed in the retina – only cloned from human
Term
What are the metabotropic receptors for Glutamate?
Definition
mGluR1 – mGluR8
They have Slow, modulatory effects
Term
What are the ionotropic receptors for Glutamate?
Definition
AMPA, kainate, NMDA
Fast synaptic transmission
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