The conversion of pyruvate to acetyl-CoA by the pyruvate dehydrogenase complex is a pivotal step linking glycolysis to the citric acid cycle. This reaction involves the decarboxylation of pyruvate, releasing carbon dioxide (CO₂). When studying metabolic pathways using radiolabeled glucose, identifying which carbon atoms are released as CO₂ helps trace the biochemical fate of glucose carbons.

This article explains which carbon atoms in glucose must be radiolabeled to observe the evolution of ¹⁴CO₂ during pyruvate decarboxylation.

Background: Glycolysis and Pyruvate Structure

Glucose is a six-carbon sugar (C1 to C6). During glycolysis, it is split into two molecules of pyruvate, each containing three carbons (numbered C1, C2, C3 in pyruvate).

• The carbons in glucose are rearranged during glycolysis, but the numbering in pyruvate corresponds as follows:

  • Glucose C1, C2, and C3 become pyruvate carbons C3, C2, and C1 respectively in one molecule.

  • The other pyruvate molecule contains glucose carbons C4, C5, and C6.

Pyruvate Decarboxylation and CO₂ Release

The pyruvate dehydrogenase complex catalyzes the oxidative decarboxylation of pyruvate:

• The carboxyl group (C1) of pyruvate is removed as CO₂.

• The remaining two carbons form acetyl-CoA.

Thus, only the C1 carbon of pyruvate is released as CO₂ during this step.

Mapping Back to Glucose Carbons

Since pyruvate is derived from glucose, to track the carbon released as CO₂, the radiolabel must be on the glucose carbon that becomes C1 of pyruvate.

• This corresponds to C3 or C4 of glucose, depending on which pyruvate molecule is considered.

Therefore, labeling carbon 3 or carbon 4 of glucose will result in the release of ¹⁴CO₂ during pyruvate decarboxylation.

Summary of Options

Conclusion

To observe the evolution of ¹⁴CO₂ during the conversion of pyruvate to acetyl-CoA, the third or fourth carbon of glucose must be radiolabeled prior to glycolysis.

Correct answer: (3) C3 or C4