SECTION 6: KETONE BODIES & CHOLESTEROL

Ketone Bodies – What are they?

Acetoacetate, β-hydroxybutyrate, and acetone. Made from excess Acetyl CoA in the liver. Water-soluble fuel that can cross the blood-brain barrier.

Ketone Bodies – When & Why Produced

Produced during low carbohydrate states (starvation, low-carb diets, uncontrolled diabetes). Oxaloacetate is depleted (used for gluconeogenesis), so Acetyl CoA can't enter Krebs → liver makes ketone bodies instead.

Ketoacidosis

Excessive ketone bodies lower blood pH. Dangerous in uncontrolled Type 1 diabetes. Symptoms: fruity breath (acetone), nausea, confusion.

HMG-CoA & Cholesterol Synthesis

Acetyl CoA → HMG-CoA → Mevalonate → Cholesterol. Occurs in the cytoplasm (smooth ER). Key enzyme: HMG-CoA Reductase (rate-limiting step).

HMG-CoA Reductase – Hormone Control

Insulin activates it (more cholesterol synthesis when fed). Glucagon inhibits it (less synthesis when fasting).

Statin Drugs

Competitive inhibitors of HMG-CoA Reductase. Block the rate-limiting step of cholesterol synthesis → lower LDL ("bad") cholesterol. Examples: Lipitor, Crestor.