hard · MCAT bio-biochem

Which reasoning best resolves the apparent contradiction?

1. Succinyl-CoA enters as a cycle intermediate, but for net carbon to leave as oxaloacetate for gluconeogenesis the cycle must still regenerate the oxaloacetate it consumed, so only the small propionyl-derived increment is anaplerotically net-gluconeogenic.
2. Propionyl-CoA carbons are fully oxidized to CO_2 within a single turn of the citric acid cycle before oxaloacetate can be withdrawn, meaning essentially none of them can ever appear in newly synthesized glucose molecules under normal conditions.
3. Succinyl-CoA itself cannot directly cross the inner mitochondrial membrane on its own without prior conversion, so its carbons remain permanently trapped inside the matrix and can never reach the cytosolic gluconeogenic enzymes required for net glucose synthesis.
4. Because acetyl-CoA derived from the even-numbered carbons cannot itself be converted into glucose under any physiological circumstances, the propionyl-CoA carbons are also therefore fully and permanently blocked at the pyruvate carboxylase step of gluconeogenesis.

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