ketonebody

Ketone bodies are a group of water-soluble molecules produced by the liver mitochondria during periods of low carbohydrate availability, such as fasting, prolonged exercise, or carbohydrate-restricted diets. The three major ketone bodies are acetoacetate, beta-hydroxybutyrate, and acetone. Although they are derived from fatty acid oxidation, the liver lacks the enzyme thiophorase needed to reuse them, so they are released into the bloodstream rather than burned in the liver.

In peripheral tissues, acetoacetate and beta-hydroxybutyrate serve as alternative energy substrates. They are taken up by cells via monocarboxylate transporters and converted back to acetyl-CoA, which enters the tricarboxylic acid cycle to generate ATP. Acetone is a volatile byproduct formed from acetoacetate and is typically exhaled, sometimes producing a characteristic breath odor in ketosis.

The production and utilization of ketone bodies are regulated by hormonal and metabolic signals. Low insulin and high glucagon promote lipolysis and fatty acid oxidation, increasing acetyl-CoA supply for ketogenesis. The interconversion between acetoacetate and beta-hydroxybutyrate depends on the cellular NAD+/NADH ratio, with high NADH favoring beta-hydroxybutyrate accumulation.

Clinical relevance includes physiological ketosis during fasting and prolonged exercise, as well as pathological states such as diabetic ketoacidosis and alcoholic ketoacidosis, in which excessive ketone bodies cause acidosis. Ketone bodies can be measured in blood or urine for diagnostic and management purposes, and exogenous ketones or ketogenic diets are studied for potential therapeutic effects in various conditions.