Regulation

Ketogenesis has to be regulated as every time fatty acids are released by the lipolysis of triglycerides, there exists the potential for unlimited ketone body formation. Control is achieved by:

• limiting hepatic blood supply. In exercise, blood is shunted away from the liver to muscle. This ensures fatty acids are utilized for energy rather than conversion to ketone bodies.
• ketone bodies providing negative feedback on the production of fatty acids:
  • promoting insulin secretion from pancreas
  • increasing sensitivity of tissue to insulin
  • inhibit lipase responsible for triglyceride breakdown in adipose tissue
• insulin acting on liver:
  • stimulates esterification to triglyceride
  • retarding transport of fatty acids into mitochondria for oxidation
• acetoacetyl coenzyme A, an early product of the ketogenesis pathway, inhibits both enzymes which form it and enzymes further forward in the pathway
• intracellular carbohydrate levels; reduced concentration of carbohydrate limits the formation of oxaloacetate to combine with acetyl CoA residues in the tricarboxylic acid cycle. Instead, acetyl CoA is shunted to ketogenesis.