Ketone body

Ketone bodies are three related molecules made in liver mitochondria from acetyl CoA: acetoacetate, beta-hydroxybutyrate and acetone. When glucose and insulin are low, as in fasting, very low-carbohydrate diets or untreated diabetes, fat stores release fatty acids that the liver breaks down by beta oxidation faster than its citric acid cycle can use the resulting acetyl CoA. The surplus is joined into acetoacetate, much of which is converted to beta-hydroxybutyrate, the main ketone body in the blood, even though it is not strictly a ketone. A little acetoacetate breaks down into acetone, which is breathed out.

Unlike fatty acids, ketone bodies dissolve in blood and reach the brain. Heart and skeletal muscle and, after a few days of fasting, the brain take them up and turn them back into acetyl CoA to burn for energy. The liver makes ketone bodies but cannot use them, because it lacks an enzyme needed to break them down.

Acetoacetate and beta-hydroxybutyrate are acids. A steady, moderate rise, called ketosis, is normal during fasting, but a rapid buildup can overwhelm the blood's buffers and cause ketoacidosis. Diabetic ketoacidosis, seen mostly in type 1 diabetes, is a medical emergency marked by high blood glucose, acidic blood and often a fruity smell of acetone on the breath, and blood or urine ketone tests help detect it.