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Ketone bodies are water-soluble molecules or compounds that contain the ketone groups produced from fatty acids by the liver (ketogenesis). [1] [2] Ketone bodies are readily transported into tissues outside the liver, where they are converted into acetyl-CoA (acetyl-Coenzyme A) – which then enters the citric acid cycle (Krebs cycle) and is oxidized for energy.
Ketogenesis is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids. [ 1 ] [ 2 ] The process supplies energy to certain organs, particularly the brain , heart and skeletal muscle , under specific scenarios including fasting , caloric restriction , sleep, [ 3 ] or others.
The resulting ketone bodies cannot be used for energy by the liver so are exported from the liver to supply energy to the brain and peripheral tissues. In addition to fatty acids, deaminated ketogenic amino acids can also be converted into intermediates in the citric acid cycle and produce ketone bodies. [11]
The ketone bodies are possibly anticonvulsant; in animal models, acetoacetate and acetone protect against seizures. The ketogenic diet results in adaptive changes to brain energy metabolism that increase the energy reserves; ketone bodies are a more efficient fuel than glucose, and the number of mitochondria is increased.
The ketones are released by the liver into the blood. All cells with mitochondria can take up ketones from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the gluconeogenic pathway in the way that this can occur in the liver.
The ketones produced become abundant in the bloodstream. Ketoacidosis is caused by the uncontrolled production of ketone bodies . Usually the production of ketones is carefully controlled by several hormones, most importantly insulin .
Ketone bodies are elevated in the blood after fasting, including a night of sleep; in both blood and urine in starvation; in hypoglycemia, due to causes other than hyperinsulinism; in various inborn errors of metabolism, and intentionally induced via a ketogenic diet, and in ketoacidosis (usually due to diabetes mellitus).
DKA results from a shortage of insulin; in response, the body switches to burning fatty acids, which produces acidic ketone bodies. [3] DKA is typically diagnosed when testing finds high blood sugar, low blood pH and keto acids in either the blood or urine. [1] The primary treatment of DKA is with intravenous fluids and insulin. [1]