22.3.6. Ketone Bodies Are a Major Fuel in Some Tissues

The major site of production of acetoacetate and 3-hydroxybutyrate is the liver. These substances diffuse from the liver mitochondria into the blood and are transported to peripheral tissues. These ketone bodies were initially regarded as degradation products of little physiological value. However, the results of studies by George Cahill and others revealed that these derivatives of acetyl CoA are important molecules in energy metabolism. Acetoacetate and 3-hydroxybutyrate are normal fuels of respiration and are quantitatively important as sources of energy. Indeed, heart muscle and the renal cortex use acetoacetate in preference to glucose. In contrast, glucose is the major fuel for the brain and red blood cells in well-nourished people on a balanced diet. However, the brain adapts to the utilization of acetoacetate during starvation and diabetes (Sections 30.3.1 and 30.3.2). In prolonged starvation, 75% of the fuel needs of the brain are met by ketone bodies.