Ketolytic

Ketolytic is an adjective relating to ketolysis, the metabolic process by which ketone bodies are converted into usable energy in the form of acetyl-CoA. In mammalian metabolism, ketolysis happens primarily in extrahepatic tissues, because the liver itself lacks the key enzymes to fully utilize ketone bodies for energy.

During periods of fasting, prolonged carbohydrate restriction, or intense exercise, the liver produces ketone bodies—acetoacetate, 3-hydroxybutyrate (beta-hydroxybutyrate), and small amounts of acetone. These ketones are released into the bloodstream and transported to tissues such as heart, skeletal muscle, and the brain, where they can be used as a fuel source.

The main steps of ketolysis in mitochondria involve several enzymes. First, acetoacetate is activated to acetoacetyl-CoA by succinyl-CoA:acetoacetate transferase (SCOT), using succinyl-CoA as a CoA donor. In parallel, 3-hydroxybutyrate can be oxidized to acetoacetate by 3-hydroxybutyrate dehydrogenase, generating NADH. Next, thiolase cleaves acetoacetyl-CoA into two acetyl-CoA units, which enter the citric acid cycle to produce energy.

Physiologically, ketolysis provides a crucial energy supply when glucose is limited. The brain, heart, and skeletal muscles increase ketone utilization during fasting or ketogenic states. Defects in ketolysis are rare metabolic disorders and can impair ketone body utilization, potentially causing energy deficiency during fasting.