Describe the formation and utilisation of ketone bodies. Add a note on ketosis.

1. 1 · Open in two lines. Ketone bodies (acetoacetate, β-hydroxybutyrate and acetone) are water-soluble fuels made in the liver from surplus acetyl-CoA. They rise when fat breakdown is high and carbohydrate is low.
2. 2 · Draw the pathway. [Diagram: in liver mitochondria, acetyl-CoA → acetoacetyl-CoA → HMG-CoA → acetoacetate, branching to β-hydroxybutyrate and acetone; arrow to muscle, where acetoacetate → acetyl-CoA → TCA cycle]
3. 3 · Ketogenesis (liver mitochondria).
   • 2 acetyl-CoA → acetoacetyl-CoA (thiolase).
   • Add acetyl-CoA → HMG-CoA (HMG-CoA synthase, the regulatory step).
   • HMG-CoA → acetoacetate + acetyl-CoA (HMG-CoA lyase).
   • Acetoacetate → β-hydroxybutyrate (dehydrogenase) or → acetone (spontaneous).
4. 4 · Ketolysis (extra-hepatic tissues). β-Hydroxybutyrate → acetoacetate; thiophorase transfers CoA from succinyl-CoA; thiolase gives 2 acetyl-CoA for the TCA cycle. The liver lacks thiophorase, so it cannot use ketone bodies.
5. 5 · Ketosis and ketoacidosis. Excess ketone bodies in blood and urine is ketosis (starvation, uncontrolled diabetes). When they lower blood pH it is ketoacidosis: fruity breath, deep breathing, dehydration. Rothera's test detects urine ketones.
6. 6 · Significance. Spare glucose in starvation. Fuel for heart and muscle, and for the brain in long fasting. Water-soluble, so they need no carrier in blood.
7. 7 · Nutrition link. Enough carbohydrate prevents starvation ketosis; good diabetes control prevents ketoacidosis; ketogenic diets need supervision.
8. 8 · Close in one line. Sum up ketone bodies as a useful fuel in fasting that becomes dangerous when uncontrolled.

Scoring tip: Show liver and muscle side by side in the diagram; it explains at a glance why the liver makes but cannot use ketone bodies.