From the Research
The answer is E. Succinyl CoA. During starvation, the brain adapts to use ketone bodies (primarily acetoacetate and β-hydroxybutyrate) as alternative fuel sources to spare glucose. When ketone bodies are metabolized, they are first converted to acetoacetyl-CoA, which is then cleaved to form two molecules of acetyl-CoA. These acetyl-CoA molecules enter the TCA cycle by condensing with oxaloacetate. However, the direct connection between ketone body metabolism and the TCA cycle involves succinyl-CoA. Specifically, the ketone body acetoacetate can be metabolized to acetoacetyl-CoA, which can then be converted to acetyl-CoA and subsequently enter the TCA cycle. Additionally, the ketone body β-hydroxybutyrate is converted to acetoacetate before following this pathway. Succinyl-CoA is directly involved in this process as it can interact with acetoacetate through the enzyme succinyl-CoA:acetoacetate CoA-transferase, which is particularly active in brain tissue during starvation. This enzyme transfers the CoA group from succinyl-CoA to acetoacetate, forming acetoacetyl-CoA and succinate, thus allowing ketone bodies to enter the energy-producing pathways.
The most recent and highest quality study that supports this answer is not explicitly provided in the given evidence, but based on the information available, the role of succinyl-CoA in ketone body metabolism is well-established 1. The TCA cycle and its intermediates play a crucial role in regulating various cellular functions, including energy production and immune responses 2. During starvation, the brain's ability to utilize ketone bodies as an energy source is critical for survival, and succinyl-CoA is a key intermediate in this process.
Some key points to consider:
- The brain's adaptation to use ketone bodies during starvation is a critical mechanism for sparing glucose and minimizing muscle protein breakdown.
- The metabolism of ketone bodies involves their conversion to acetoacetyl-CoA, which can then be converted to acetyl-CoA and enter the TCA cycle.
- Succinyl-CoA is directly involved in the metabolism of ketone bodies through its interaction with acetoacetate via the enzyme succinyl-CoA:acetoacetate CoA-transferase.
- The TCA cycle and its intermediates, including succinyl-CoA, play a crucial role in regulating energy production and other cellular functions.
Overall, the evidence suggests that succinyl-CoA is the most likely intermediate of the TCA cycle to play a direct role in the utilization of ketone bodies in the brain during starvation 3, 1.