ketogenes

Ketogenes is a term sometimes used to describe the set of genes that encode the enzymes and regulatory proteins involved in ketogenesis, the hepatic production of ketone bodies. Ketogenesis occurs primarily in liver mitochondria during fasting, prolonged exercise, or carbohydrate restriction, when fatty acids are mobilized and converted into ketone bodies that can provide energy to extrahepatic tissues.

The core ketogenesis pathway involves several enzymes. Thiolase (ACAA2) condenses two acetyl-CoA units to acetoacetyl-CoA. 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) then converts acetoacetyl-CoA to HMG-CoA, which is cleaved by 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) to acetoacetate. Acetoacetate can be reduced to beta-hydroxybutyrate by beta-hydroxybutyrate dehydrogenase 1 (BDH1); some acetoacetate may be decarboxylated to acetone. Regulatory inputs include transcriptional programs driven by PPAR-alpha, PGC-1alpha, and energy-sensing pathways such as AMPK, which coordinate expression and activity of the ketogenesis enzymes.

Regulation and physiology: Ketogenesis is tightly regulated to balance energy supply and glucose homeostasis. In humans, congenital deficiencies of HMGCS2 or HMGCL disrupt ketone production and can cause hypoketotic hypoglycemia with metabolic crises. Under normal conditions, ketogenes respond to fasting, prolonged exercise, and ketogenic diets, supporting brain and other tissues when glucose is scarce.

Terminology and usage: The term ketogenes is not uniformly used in the literature; more common references describe the ketogenesis enzymes (ACAA2, HMGCS2, HMGCL, BDH1) and their regulatory genes. The concept remains useful as a concise way to refer to the gene set coordinating hepatic ketone-body production.