GABA and Glycine

Question 1

How is GABA synthesis and stored?

Answer 1

Glutamate → GABA via glutamate decarboxylase with co-factor pyridoxal phosphate from vitB6 (absent of vitB6 = decreased GABA synthesis = seizures)

Transported by vesicular inhibitory amino acid transporters (VIAAT)

Glutmate precursor is stored in rounded vesicles whereas GABA is stored in oval shaped vesicles

Question 2

How is GABA re-uptaken and degraded?

Answer 2

Re-uptake: GAT (Na2+ dependant GABA re-uptake transporters) on neurones (GAT1) and glial cells (GAT3)

GABA → Succinic semialdehyde via GABA transaminase (GABA-T)

Succinic semialdehyde → succinic acid via succinic semialdehyde dehydrogenase (SSADH)

Question 3

What are the ionotropic GABA receptors?

Answer 3

GABA-a receptors

Pentameric: 6 𝝰, 3 𝝱 and 3 𝝲

= influx of Cl- thus hyperpolarisation, leading to a need of increased stimulus for AP

Question 4

What are the metabotropic GABA receptors?

Answer 4

GABA-b receptors

GABA binding for dimerization = heteromeric of GABA-b1 and GABA-b2

Gi/o thus ↓AC and ↓cAMP and ↑K+ efflux

Also blocks Ca2+ channels

Question 5

What is the purpose of GABA projections in the cerebellum?

Answer 5

Purkinje cells are GABAergic

Sends GABAergic projections to deep cerebellar neurons

Generates an error connection signal that can modify movements, precision

Question 6

What drugs are used to enhance GABA?

Answer 6

GABAa receptor enhancers - Barbiturates & benzodiazepines

GAT blockers - tiagabine

GABA-transaminase inhibitor - vigabatrine

GAD modulators - Gabapentin & valproate

Question 7

How is glycine synthesised and stored?

Answer 7

3-phosphoglycerate → serine → glycine via serine hydroxymethyl-transferase

Transported into oval vesicles by VIAAT

Question 8

How is gycine re-uptaken and degraded?

Answer 8

GlyT (Na+ dependant glycine re-uptake transporters) glial cell GlyT-1 and neurones GlyT-2

Glycine → serine via serine hydroymethyl-transferase

Question 9

Where is the strcture of glycine receptors and where are they found?

Answer 9

Pre and post synaptic membranes

pentameric, 4 𝝰 subtypes, 1 𝝱 subtype

Question 10

What is the role of glycine

Answer 10

Regulate stimulation

decreased glycine = hypertonia (increased muscle tone) and exaggerated startle response