Overview
This lecture explains what ketones are, how and when they are produced, their role as a fuel source, the difference between ketosis and ketoacidosis, and factors that affect ketone production.
What Are Ketones?
- Ketones are energy molecules produced when the body lacks enough carbohydrates.
- They are made in the liver from excess acetyl-CoA when the Krebs cycle can't keep up.
- Common scenarios for ketone production include low-carb/ketogenic diets and uncontrolled diabetes.
Ketone Production & Metabolism
- Beta-oxidation of fatty acids increases acetyl-CoA, leading to ketone formation.
- HMG CoA is an intermediate in ketone synthesis and also a cholesterol precursor.
- The main ketone bodies are acetoacetate and beta-hydroxybutyrate.
- Beta-hydroxybutyrate is the primary circulating ketone; excess ketones produce acetone, causing fruity-smelling breath.
- Ketones are converted back to acetyl-CoA and used in the Krebs cycle for energy.
- Full oxidation of acetoacetate yields 2 GTP and 22 ATP.
Ketones as a Fuel Source
- Ketones can be used by the brain, heart, muscle, and intestines for energy.
- Some brain cells can utilize ketones similarly to how they use lactate.
- Ketones provide a significant, efficient energy source during periods of low carbohydrate intake.
Ketosis vs. Ketoacidosis
- Ketosis: safe state with low ketone levels due to fasting or ketogenic diets.
- Ketoacidosis: dangerous, high ketone levels (15–25 mM) in uncontrolled diabetes, causing acidosis and dehydration.
- Ketosis usually involves much lower ketone levels (max ~6 mM in prolonged fasting).
- Ketoacidosis requires urgent medical intervention to control glucose, ketones, and dehydration.
Factors That Affect Ketone Production
- Ketones are produced when carbohydrate intake is low and pyruvate is depleted.
- High protein intake can prevent ketosis by providing substrates for the Krebs cycle.
- Ketogenic diets require low carbs and moderate to low protein intake.
- Increased gluconeogenesis (from high stress or lack of sleep) raises blood glucose and inhibits ketone production.
- Protein, sleep, and stress all influence the body’s ability to enter or maintain ketosis.
Key Terms & Definitions
- Ketone Bodies — energy molecules (acetoacetate, beta-hydroxybutyrate, acetone) made from fat when carbs are scarce.
- Krebs Cycle — major energy-producing pathway in cells.
- Beta-oxidation — process of breaking down fatty acids into acetyl-CoA.
- Ketosis — state of elevated, but safe, ketone levels from low carbohydrate intake.
- Ketoacidosis — dangerous over-accumulation of ketones causing blood acidification, mostly in diabetics.
Action Items / Next Steps
- Monitor protein, stress, and sleep levels if attempting a ketogenic diet.
- Distinguish clearly between ketosis (safe) and ketoacidosis (dangerous).
- Review assigned readings on metabolism and ketone biochemistry if provided.