What determines the rate of ketogenesis during starvation?

• A. The rate of gluconeogenesis
• B. The supply of fatty acids and the regulation of fatty acid oxidation, promoted by low insulin
• C. The level of circulating glucose
• D. The amount of glycogen stored

Answer: (B)

Ketogenesis during starvation is driven by the flux of fatty acids into the liver and how their oxidation is regulated, not by glucose level or glycogen storage. When insulin is low, adipose tissue lipolysis is stimulated, releasing fatty acids into the bloodstream. These fatty acids are delivered to the liver and enter mitochondria for beta-oxidation, generating acetyl-CoA. A key regulatory step is malonyl-CoA, which inhibits the enzyme that transports fatty acids into mitochondria. Low insulin lowers malonyl-CoA, lifting this brake and increasing fatty acid oxidation. The liver then has plenty of acetyl-CoA, and as oxaloacetate is diverted toward gluconeogenesis, acetyl-CoA is channeled into ketone body production. So the rate of ketogenesis hinges on the fatty acid supply and the hormonal control of their oxidation, promoted by low insulin. Glucose level or glycogen stores influence insulin and energy status but do not directly determine ketogenesis rate to the same extent.