Ketone Bodies : Alternative Fuel For Cells

Liver mitochondria have the capacity to convert acetyl CoA derived from fatty acid oxidation into ketone bodies. The compounds categorized as ketone bodies are acetoacetate, 3-hydroxybutyrate (also called β-hydroxybutyrate), and acetone (a nonmetabolized side product, Fig. 1). [Note: The two functional ketone bodies are organic acids.] Acetoacetate and 3-hydroxybutyrate are transported in the blood to the peripheral tissues. There they can be reconverted to acetyl CoA, which can be oxidized by the TCA cycle.

Ketone bodies are important sources of energy for the peripheral tissues because they 1) are soluble in aqueous solution and, therefore, do not need to be incorporated into lipoproteins or carried by albumin as do the other lipids; 2) are produced in the liver during periods when the amount of acetyl CoA present exceeds the oxidative capacity of the liver; and 3) are used in proportion to their concentration in the blood by extrahepatic tissues, such as skeletal and cardiac muscle, the intestinal mucosa, and the renal cortex. Even the brain can use ketone bodies to help meet its energy needs if the blood levels rise sufficiently. Thus, ketone bodies spare glucose, which is particularly important during prolonged periods of fasting . [Note: Disorders of fatty acid oxidation present with the general picture of hypoketosis (because of decreased availability of acetyl CoA) and hypoglycemia (because of increased reliance on glucose for energy).]

Figure 1: Synthesis of ketone bodies. [Note: The release of CoA in ketogenesis supports continued fatty acid oxidation.] CoA = coenzyme A; HMG = hydroxymethylglutarate; NAD(H) = nicotinamide adenine dinucleotide; CO2 = carbon dioxide.