From the Research
During prolonged fasting, acetyl-CoA is the product that allosterically activates pyruvate carboxylase for gluconeogenesis. This process is crucial for maintaining blood glucose levels, especially for glucose-dependent tissues like the brain. When fasting extends beyond 24 hours, the body shifts to using fatty acids as its primary fuel source, resulting in increased fatty acid oxidation and high levels of acetyl-CoA in the liver.
Key Points
- Acetyl-CoA serves as an allosteric activator by binding to pyruvate carboxylase, significantly enhancing its activity 1.
- This activation is crucial because pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate, which is the first committed step in gluconeogenesis.
- The regulatory mechanism of acetyl-CoA on pyruvate carboxylase represents an elegant metabolic adaptation that links increased fat metabolism during fasting directly to enhanced glucose production, helping to preserve homeostasis during periods of food deprivation 2, 3.
- The most recent and highest quality study on this topic, published in 2022, provides mechanistic insight into the allosteric activation of human pyruvate carboxylase by acetyl-CoA, further supporting the importance of this regulatory mechanism 1.