Which ONE of the following statements about the transmitter glutamate is CORRECT?

Question

Which ONE of the following statements about the transmitter glutamate is CORRECT?

BlackTom AI · Accepted Answer

Glutamate in the CNS is mainly synthesized from glutamine and from glucose-derived TCA cycle intermediates.

1. Relevant knowledge points and concepts
- Glutamate is the principal excitatory neurotransmitter in the brain.
- Two major synthetic routes: the glutamate–glutamine cycle between neurons and astrocytes, and de novo synthesis from glucose via the tricarboxylic acid (TCA) cycle (alpha‑ketoglutarate).
- Key enzymes: glutamine synthetase (astrocytes), phosphate‑activated glutaminase (neurons), glutamate dehydrogenase and aminotransferases (for TCA-derived synthesis).

2. Step‑by‑step reasoning process
- Neurons release glutamate into the synapse during neurotransmission.
- Astrocytes rapidly take up synaptic glutamate to prevent excitotoxicity.
- In astrocytes, glutamate + NH4+ + ATP is converted to glutamine by glutamine synthetase.
- Glutamine is transported back to neurons where phosphate‑activated glutaminase converts it to glutamate, replenishing the neuronal pool.

3. Biochemical intermediate steps (detailed)
- From glucose: glucose → glycolysis → pyruvate → pyruvate dehydrogenase → acetyl‑CoA → TCA cycle → formation of alpha‑ketoglutarate.
- Alpha‑ketoglutarate + NH4+ + NAD(P)H → glutamate (via glutamate dehydrogenase) OR
- Alpha‑ketoglutarate + amino acid ↔ glutamate + corresponding ketoacid (via aminotransferases, e.g., aspartate aminotransferase).
- Glutamate in astrocytes + ATP + NH4+ → glutamine (glutamine synthetase); glutamine → glutamate in neurons (glutaminase).

4. Why the correct answer is correct
These pathways show that neuronal glutamate is predominantly supplied either by reconversion of glutamine provided by astrocytes or by synthesis from glucose carbon skeletons through alpha‑ketoglutarate. Dietary glutamate and peripheral pools do not significantly supply brain glutamate because the blood–brain barrier limits direct uptake.

5. Why other possible statements would be incorrect
- Claiming glutamate is mainly imported from blood is false (BBB restricts uptake).
- Saying glutamate is synthesized primarily from GABA is incorrect: GABA is produced from glutamate, not the reverse as a primary source.
- Asserting neurons lack a glutamine supply ignores the astrocyte–neuron glutamine shuttle that is well established.

6. Conclusion
This reasoning confirms the correct answer: In the brain, glutamate is predominantly derived from glutamine or glucose.

Which ONE of the following statements about the transmitter glutamate is CORRECT?Single choice

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