hard · MCAT bio-biochem
During fatty acid oxidation of an odd-chain fatty acid, the final three-carbon unit yields propionyl-CoA, which is converted to succinyl-CoA and enters the citric acid cycle. A clinician notes that despite this entry, odd-chain fatty acids are NOT a meaningful source of net glucose under most conditions.
Which reasoning best resolves the apparent contradiction?
- 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.
- Propionyl-CoA carbons are fully oxidized to CO_2 within one turn of the cycle, so none of them can ever appear in glucose.
- Succinyl-CoA cannot cross the mitochondrial membrane, so its carbons are trapped and never reach the cytosolic gluconeogenic enzymes.
- Because acetyl-CoA from the even-numbered carbons cannot be made into glucose, the propionyl-CoA carbons are also blocked at the pyruvate carboxylase step.
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