Ketogenesis

Ketogenesis is the production of ketone bodies from acetyl-CoA, primarily in liver mitochondria when carbohydrate availability is low. It converts fatty-acid-derived carbon into fuels that other tissues can use.

Acetyl-CoA: A two-carbon molecule that carries acetyl groups into metabolic pathways, including the citric acid cycle and ketogenesis. It supplies the carbon atoms that ketogenesis assembles into ketone bodies.
Fatty acid oxidation: The breakdown of fatty acids into acetyl-CoA, NADH, and FADH2, chiefly in mitochondria. It supplies much of the acetyl-CoA and reducing power used during fasting ketogenesis.
Ketone bodies: The water-soluble metabolites acetoacetate, beta-hydroxybutyrate, and acetone produced during ketogenesis. Ketogenesis is the pathway that produces this family of metabolites.
Gluconeogenesis: The synthesis of glucose from non-carbohydrate precursors, especially during fasting. It competes for oxaloacetate as the liver simultaneously increases ketone production.
HMG-CoA synthase 2: A mitochondrial enzyme that catalyzes formation of HMG-CoA from acetyl-CoA and acetoacetyl-CoA. It catalyzes the rate-limiting step of hepatic ketogenesis.
Lipolysis: The hydrolysis of stored triacylglycerols into fatty acids and glycerol. It releases fatty acids that the liver can oxidize to support ketogenesis.
Ketolysis: The use of ketone bodies by extrahepatic tissues, converting them into acetyl-CoA for energy. It completes ketone-body fuel use after the liver exports its products.
Citric acid cycle: A cyclic mitochondrial pathway that oxidizes acetyl-CoA and generates reducing equivalents for ATP production. When its capacity to use acetyl-CoA is constrained, more acetyl-CoA can enter ketogenesis.
HMG-CoA lyase: A mitochondrial enzyme that cleaves HMG-CoA to form acetoacetate and acetyl-CoA. Its cleavage of HMG-CoA produces the first ketone body.
Glucagon: A pancreatic hormone that raises blood glucose and promotes fuel mobilization during fasting. Its fasting signals favor fatty-acid delivery and hepatic ketone production.

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