Ketone Bodies
High-Yield Summary
- During fasting, liver acetyl-CoA accumulates because oxaloacetate is diverted to gluconeogenesis, limiting citric acid cycle capacity — this triggers ketogenesis in liver mitochondria.
- Ketogenesis: 2 acetyl-CoA → HMG-CoA (HMG-CoA synthase) → acetoacetate (HMG-CoA lyase). Acetoacetate either spontaneously becomes acetone (exhaled — fruity breath) or is converted to beta-hydroxybutyrate (uses NADH).
- Ketolysis (peripheral tissues — muscle, renal cortex, brain during fasting): beta-hydroxybutyrate → acetoacetate → acetoacetyl-CoA (via SCOT) → 2 acetyl-CoA → citric acid cycle.
- The liver lacks SCOT — it can make ketone bodies but cannot use them for its own energy, a deliberate division of labor.
- During prolonged starvation, the brain derives up to two-thirds of its energy from ketone bodies, sparing glucose and muscle protein.
Key Terms
- Ketogenesis
- Liver-mitochondria pathway converting excess acetyl-CoA into acetoacetate and beta-hydroxybutyrate.
- Ketolysis
- Peripheral-tissue pathway converting ketone bodies back into acetyl-CoA for the citric acid cycle.
- SCOT
- Succinyl-CoA:3-ketoacid CoA transferase — converts acetoacetate to acetoacetyl-CoA; absent in the liver.
Ketogenesis (Liver)
- 12 acetyl-CoA combine → HMG-CoA (HMG-CoA synthase)
- 2HMG-CoA → acetoacetate (HMG-CoA lyase)
- 3Acetoacetate → acetone (spontaneous, exhaled) OR → beta-hydroxybutyrate (uses NADH → NAD⁺)
Ketolysis (Peripheral Tissues)
- 1Beta-hydroxybutyrate → acetoacetate (generates NADH)
- 2Acetoacetate → acetoacetyl-CoA (SCOT)
- 3Acetoacetyl-CoA → 2 acetyl-CoA → citric acid cycle → NADH/FADH₂ → ATP
The Three Ketone Bodies
| Ketone Body | Formation / Fate |
|---|---|
| Acetoacetate | From HMG-CoA lyase / → acetone or beta-hydroxybutyrate |
| Beta-hydroxybutyrate | Acetoacetate + NADH / Released into blood, reconverted in tissues |
| Acetone | Spontaneous from acetoacetate / Exhaled (fruity breath) |
Common MCAT Trap
- The liver MAKES ketone bodies but cannot USE them — it lacks SCOT. Don't assume an organ benefits from what it produces.
- Acetone formation is spontaneous (non-enzymatic), not catalyzed — distinguish this from the enzyme-driven beta-hydroxybutyrate pathway.
- Ketosis (elevated ketone bodies) is a normal fasting adaptation, distinct from pathological diabetic ketoacidosis — the biochemistry note focuses on normal physiology here.
Quick Recall
Why does the liver start producing ketone bodies during fasting?
Why can't the liver use its own ketone bodies?
What causes the fruity breath odor associated with ketosis?