Ketogenesis - Production

Production

Ketone bodies are produced mainly in the mitochondria of liver cells, and synthesis can occur in response to unavailability of blood glucose. This is caused by low glucose levels in the blood, after exhaustion of cellular carbohydrate stores, such as glycogen or, synthesis of ketones can occur due to excessively high levels of blood glucose that are unable to be stored as glycogen in liver and muscle. The production of ketone bodies is then initiated to make available energy that is stored as fatty acids. Fatty acids are enzymatically broken down in β-oxidation to form acetyl-CoA. Under normal conditions, acetyl-CoA is further oxidized and its energy transferred as electrons to NADH, FADH₂, and ATP in the citric acid cycle (TCA cycle). However, if the amounts of acetyl-CoA generated in fatty-acid β-oxidation challenge the processing capacity of the TCA cycle or if activity in the TCA cycle is low due to low amounts of intermediates such as oxaloacetate, acetyl-CoA is then used instead in biosynthesis of ketone bodies via acetoacyl-CoA and β-hydroxy-β-methylglutaryl-CoA (HMG-CoA). Deaminated amino acids that are ketogenic such as leucine also feed the TCA cycle, forming acetoacetate & ACoA and thereby produce ketones

Besides its role in the synthesis of ketone bodies, HMG-CoA is also an intermediate in the synthesis of cholesterol.