4.1 BCHM - GABA/Glycine Biochemistry

Question 1

GABAa and GABAb receptors. Ionotropic or metabotropic?

Answer 1

GABAa = ionotropic.

GABAb = metabotropic.

Question 2

Which of the following molecules is an inhibitory neurotransmitter, which is an excitatory neurotransmitter? What channels do they activate? Which is most prevalent? What are their names?

Answer 2

1) GABAa = inhibitory, activates cl- channels, most prevalent.
2) Glycine = inhibitory, activates cl- channels.

Question 3

What are the two confirmational forms that GABA can be in?

Answer 3

Cis and trans.

In cis the positive NH3+ and negative O- are attracted and interact.

Question 4

What enzyme pulls this off? Where does this occur?

Answer 4

Glutamate decarboxylase.

Presynaptic neuron.

Question 5

What type of receptor does GABA bind, ionotropic or metabotropic? What does it do at these channels (what ions involved)?

Answer 5

Both.

Let’s Cl- in cell.

Question 6

What enzyme degrades GABA in both astrocytes and presynaptic neurons? What does it get degraded into? Where can it go next?How does GABA get transported to these cells?

Answer 6

GABA transaminase degrades GABA into succinate.

GABA can be recycled into glutamate, glutamine, and alpha-ketoglutarate, or back to GABA.

If recycled into glutamate in an astrocyte it must first go to glutamine to be transferred to presynaptic neuron then to glutamate (remember this little detail?).

GABA is picked up via GABA transporters.

Question 7

What cofactor is necessary for GABA transaminase (and any transaminase for that matter)? What does this cofactor always do?

Answer 7

Pyridoxal-5-phosphate = Vitamin B-6.

Interchanges amines and aldehydes by acting as an electron sink first to accept then to donate an amine group.

Question 8

What is happening here, oxidation or reduction? Where will this succinate intermediate be used (what pathway)?

Answer 8

Oxidized.

Succinate is an intermediate in the Citric Acid Cycle.

Question 9

Check this out. Make sure to trace the pathway by which the Citric Acid Cycle converts:

glutamate -> aspartate

aspartate -> glutamate

GABA -> aspartate

aspartate -> GABA

GABA -> glutamate

Question 10

Valproic acid is the most widely prescribed anti-epileptic drug worldwide. What affects does it have on GABA, aspartate, glutamate?

Answer 10

Increase GABA.

Decrease aspartate.

No effect glutamate.

Question 11

What is the mechanism of action of Valproate? What will these actions have on the concentration of GABA?

Answer 11

Binds and inhibits GABA transaminase and alpha-ketoglutarate dehydrogenase.

Increase GABA.