Made in the liver from acetyl-CoA, used by brain, heart and muscle
Expansion
Three ketone bodies: acetoacetate, beta-hydroxybutyrate (the most abundant) and acetone (volatile, giving the characteristic breath).
Produced in hepatic mitochondria from acetyl-CoA when:
- Fatty acid oxidation is high
- Oxaloacetate is depleted by gluconeogenesis, so acetyl-CoA cannot enter the Krebs cycle
The liver cannot use ketones, lacking succinyl-CoA transferase, so it exports them all.
Used by brain, heart, skeletal muscle and renal cortex. The brain adaptation is critical: after several days of fasting, ketones supply up to two-thirds of cerebral fuel, sparing muscle protein and greatly extending survival.
Clinical states
- Physiological ketosis: fasting, ketogenic diet, prolonged exercise. Ketones rise modestly and pH is maintained
- Diabetic ketoacidosis: unrestrained lipolysis from absolute insulin deficiency, with ketones high enough to overwhelm buffering
- Alcoholic ketoacidosis and starvation ketoacidosis
Bedside meters measure beta-hydroxybutyrate, whereas urine dipsticks detect acetoacetate, which is why urine ketones can appear to rise during treatment as beta-hydroxybutyrate is converted back.