Overview
This lecture explains the biochemistry of the ketogenic diet by detailing how metabolism, hormones, and energy pathways shift when carbohydrate intake is low.
Hormonal Regulation of Blood Glucose
- Insulin lowers blood sugar by promoting glucose uptake into cells.
- Glucose in cells is stored as glycogen (glycogenesis) or converted to fat (lipogenesis).
- Glycogenesis occurs in skeletal muscles and liver; lipogenesis in fat cells and liver.
- Glucagon raises blood sugar by promoting glycogenolysis (glycogen breakdown) and gluconeogenesis (creation of glucose from non-carbs).
Energy Sources and Metabolic Pathways
- Glycogen stores last about 12-14 hours or 2 hours of moderate exercise.
- Low-carb diets, fasting, or prolonged exercise deplete glycogen stores.
- Gluconeogenesis uses glycerol from fat and glucogenic amino acids from muscle/protein.
- Prolonged fasting can lead to muscle breakdown to provide amino acids for glucose production.
Ketogenic Amino Acids and Fat Metabolism
- Ketogenic amino acids can be converted directly to acetyl-CoA, leading to ketone body production.
- Fatty acids, released by lipolysis, are oxidized to acetyl-CoA and enter the Krebs cycle for energy.
- Triglycerides are the main form of body fat; their breakdown releases fatty acids and glycerol.
Ketone Bodies and the Brain
- In absence of carbs, the liver produces ketone bodies from fatty acids and amino acids.
- Ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) can cross the blood-brain barrier and fuel the brain.
- Ketone bodies are converted to acetyl-CoA, then enter the Krebs cycle.
The Ketogenic Diet Explained
- The keto diet shifts the body from glycolysis (burning glucose) to ketosis (burning ketones).
- Diet composition: roughly 5% carbs, 15-30% protein, remainder from fat.
- Takes several days for the body to adapt to ketosis.
- Insulin drops and ketone levels rise during adaptation.
- Rapid initial weight loss is mostly water and electrolyte loss, causing “keto flu” symptoms.
- Electrolyte replenishment and hydration help relieve keto flu.
- After adaptation, reported benefits include improved mental clarity, stable energy, and reduced appetite.
- Another side effect is fruity or nail polish-like breath from ketone breakdown.
Key Terms & Definitions
- Insulin — hormone lowering blood sugar by enabling glucose uptake into cells.
- Glucagon — hormone raising blood sugar by promoting glycogen breakdown and gluconeogenesis.
- Glycogenesis — formation of glycogen from glucose.
- Lipogenesis — conversion of glucose to fat.
- Glycogenolysis — breakdown of glycogen to glucose.
- Gluconeogenesis — creation of glucose from non-carbohydrate sources.
- Ketogenic amino acids — amino acids converted directly into acetyl-CoA and ketone bodies.
- Lipolysis — breakdown of fat (triglycerides) into fatty acids and glycerol.
- Ketone bodies — alternative energy molecules (acetoacetate, beta-hydroxybutyrate, acetone) produced in low-carb states.
- Krebs cycle — cellular process converting acetyl-CoA into energy.
Action Items / Next Steps
- Research further before considering the ketogenic diet.
- Track electrolyte and water intake if attempting keto.
- Review metabolic pathways: glycolysis, Krebs cycle, gluconeogenesis, and ketosis.