Ketogenesis

Hepatic production of ketone bodies from excess acetyl-CoA during fasting.

Overview

Ketogenesis occurs in liver mitochondria when acetyl-CoA from fatty acid oxidation exceeds the capacity of the citric acid cycle (oxaloacetate depletion). Two acetyl-CoA molecules condense to form acetoacetyl-CoA, which is converted to HMG-CoA by HMG-CoA synthase, then cleaved to acetoacetate and acetyl-CoA. Acetoacetate can be reduced to β-hydroxybutyrate or spontaneously decarboxylated to acetone.

Cellular Location

Liver mitochondria

Clinical Significance

Critical fuel source for brain during prolonged fasting; diabetic ketoacidosis is a life-threatening complication; ketogenic diets exploit this pathway.

Key Molecules

Acetyl-CoA Acetoacetyl-CoA HMG-CoA Acetoacetate β-Hydroxybutyrate Acetone

Key Enzymes

Thiolase HMG-CoA synthase HMG-CoA lyase β-Hydroxybutyrate dehydrogenase

Related Pathways

β-Oxidation of Fatty Acids

Sequential removal of 2-carbon units from fatty acids as acetyl-CoA.

Gluconeogenesis

Synthesis of glucose from non-carbohydrate precursors.