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Ketogenesis takes place in the setting of low glucose levels in the blood, after exhaustion of other cellular carbohydrate stores, such as glycogen. [10] It can also take place when there is insufficient insulin (e.g. in type 1 (and less commonly type 2) diabetes), particularly during periods of "ketogenic stress" such as intercurrent illness. [4]
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.
The beginning of this process takes place in the mitochondrial matrix, where pyruvate molecules are found. A pyruvate molecule is carboxylated by a pyruvate carboxylase enzyme, activated by a molecule each of ATP and water. This reaction results in the formation of oxaloacetate. NADH reduces oxaloacetate to malate.
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.
Oxaloacetate is reduced to malate using NADH, a step required for its transportation out of the mitochondria. Malate is oxidized to oxaloacetate using NAD + in the cytosol, where the remaining steps of gluconeogenesis take place. Oxaloacetate is decarboxylated and then phosphorylated to form phosphoenolpyruvate using the enzyme PEPCK.
Ketosis is a metabolic state characterized by elevated levels of ketone bodies in the blood or urine. Physiological ketosis is a normal response to low glucose availability. . In physiological ketosis, ketones in the blood are elevated above baseline levels, but the body's acid–base homeostasis is maintain
However, drinking exogenous ketones will not trigger fat burning like a ketogenic diet. Most supplements rely on β-hydroxybutyrate as the source of exogenous ketone bodies. It is the most common exogenous ketone body because of its efficient energy conversion and ease of synthesis. [1] In the body, β-HB can be converted to acetoacetic acid.
A young adult human's fat stores average between about 15–20 kg (33–44 lb), but varies greatly depending on age, sex, and individual disposition. [10] In contrast, the human body stores only about 400 g (0.9 lb) of glycogen , of which 300 g (0.7 lb) is locked inside the skeletal muscles and is unavailable to the body as a whole.