In going from acetyl-CoA to succinate, two carbons have entered the cycle and two have been released as CO2. Why is the cycle not considered as complete at this point?

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Question restatement: In going from acetyl-CoA to succinate, two carbons have entered the cycle and two have been released as CO2. Why is the cycle not considered as complete at this point?

Option 1: Not enough NADH has been generated.
This option surfaces a common idea that energy carriers like NADH determine completeness. However, regardless of the amount of NADH produced so far, the krebs cycle continues as long as acetyl-CoA is fed into the cycle and oxaloacetate is regenerated for another turn. The immediate issue at this stage is not the NADH yield deficit but the need to regenerate the starting molecule, oxaloacetate, to continue running the cycle.

Option 2: The cell requires FADH2 produced in subsequent reactions of the cycle.
FADH2 is indeed produced later in the cycle (specifically at succinate dehydrogenase), but the production of FADH2 in later steps does not address why the cycle is not complete after two turns. The cycle’s completeness is not defined by a lack of FADH2 at this exact point; rather, it hinges on regenerating oxaloacetate to accept another acetyl group.

Option 3: The oxaloacetate used to initiate the cycle must be regenerated.
This is a central concept: acetyl-CoA condenses with oxaloacetate to form citrate, kickstarting the cycle. After two carbons have entered and two CO2 are released, oxaloacetate has been decarboxylated and replaced, but the cycle cannot proceed to process another acetyl-CoA until oxaloacetate is regenerated. Thus, the cycle is not complete because the starting four-carbon oxaloacetate must be reformed to continue.

Option 4: Not enough energy has been generated from the cycle at this stage.
Energy generation is a byproduct of the cycle, via NADH and FADH2 feeding into oxidative phosphorylation. The concept of the cycle being incomplete is not about reaching a threshold of energy at this exact step; rather, it’s about the regeneration of oxaloacetate to sustain continued turnover. Therefore, this option misidentifies the limiting requirement for continuing the cycle.

In summary, the critical reason the cycle isn’t complete after two carbons have entered and two have left as CO2 is because oxaloacetate, the molecule that condenses with acetyl-CoA to start the cycle, must be regenerated to allow another round of citrate formation and acetyl-CoA entry. The other options describe energy considerations or later yields that do not address the immediate biochemical prerequisite for cycle continuation.

In going from acetyl-CoA to succinate, two carbons have entered the cycle and two have been released as CO2. Why is the cycle not considered as complete at this point?

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