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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.
Depletion of glucose and oxaloacetate can be triggered by fasting, vigorous exercise, high-fat diets or other medical conditions, all of which enhance ketone production. [12] Deaminated amino acids that are ketogenic, such as leucine, also feed TCA cycle, forming acetoacetate & ACoA and thereby produce ketones. [1]
The reactions related to the urea cycle produce NADH, and NADH can be produced in two different ways. One of these uses oxaloacetate. In the cytosol there are fumarate molecules. Fumarate can be transformed into malate by the actions of the enzyme fumarase. Malate is acted on by malate dehydrogenase to become oxaloacetate, producing a molecule ...
Beta oxidation, in the mitochondrial matrix, then cuts the long carbon chains of the fatty acids (in the form of acyl-CoA molecules) into a series of two-carbon units, which, combined with co-enzyme A, form molecules of acetyl CoA, which condense with oxaloacetate to form citrate at the "beginning" of the citric acid cycle. [2]
This utilization of oxaloacetate in gluconeogenesis can make it unavailable to condense with acetyl-CoA, preventing entrance into the TCA cycle. In this scenario, energy can be harvested from acetyl-CoA through ketone production. In ketogenesis, two acetyl-CoA molecules condense to form acetoacetyl-CoA via thiolase.
The process occurs in two cellular locations: the cytosol and the mitochondria matrix. A cycle is formed by the system, ensuring that the conversion between acetylene, oxaloacetate, citrate, and malate can continue without the need for foreign molecule addition. It involves six major steps: [1] [8]
2, to interact with the saturated fatty acyl-CoA chain, forming a double bond and two molecules of water, H 2 O. Two electrons come from NADH + H + and two from the single bond in the fatty acid chain. [7] These mammalian enzymes are, however, incapable of introducing double bonds at carbon atoms beyond C-9 in the fatty acid chain. [nb 1].)
Therefore, in species that lack intra-mitochondrial PEPCK, oxaloacetate must be converted into malate or aspartate, exported from the mitochondrion, and converted back into oxaloacetate in order to allow gluconeogenesis to continue. [27] Gluconeogenesis pathway with key molecules and enzymes. Many steps are the opposite of those found in the ...