Glutamate

What is glutamate?

• one of the 20 proteogenic amino acids

• not an essential amino acid = can be synthesised

What codons code for glutamate?

• GAA

• GAG

What role does glutamate play in the body?

1. in clearance of excess nitrogen from body:

2. energy source:

3. synthesis of inhibitory neurotransmitter GABA

4. can act as excitatory neurotransmitter in CNS

How can glutamate be used for excess nitrogen clearance?

• each nitrogen is converted to urea = part of urea cycle

• non-toxic carrier of ammonium ions

• can provide initial nitrogen into urea cycle

How can glutamate be used as an energy source?

• can be converted into α-ketoglutarate (intermediate in citric acid cycle)

Where is glutamate utilised as an energy source?

• in cancers like glioma + glioblastoma = use glutamate for energy production

• particularly seen in tumours with an IDH1 mutation

How can glutamate be used for the synthesis of inhibitory neurotransmitter GABA?

• enzyme glutamate decarboxylase (GAD) converts glutamate into GABA

What can loss of enzyme glutamate decarboxylase (GAD) lead to?

• stiff person syndrome

What is stiff person syndrome caused by?

• neurological disorder involving antibodies against GAD

• loss of GAD results in lower levels of GABA

What are symptoms and signs of GAD:

• muscle stiffness

• spasms

• patients may develop diabetes mellitus due to GAD being present in pancreas

What is glutamate synthesised from?

• from glutamine by glutaminase enzyme

How can glutamate act as an excitatory neurotransmitter?

• it can bind to various receptors to have actions on post-synaptic membrane

• plays a role in long-term potentiation = important in memory and learning

What can high levels of glutamate lead to?

• high levels of glutamate may contribute to excitotoxicity that can be seen following a stroke

What are the different receptors glutamate can bind to?

• NMDA = voltage gated Ca2+ channel

• AMPA = Na+ and K+ channel

• Kainate = Na+ and K+ channel

• Metabotropic type I = Gq-coupled, phospholipase C activation

• Metabotropic type II/ III = Gi-coupled, adenylate cyclase inhibition