Ketogenesis

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Ketogenesis is a biochemical process in which an organism produces a group of substances that are collectively known as ketone bodies by the breakdown of fatty acids and ketogenic amino acids. This process supplies energy to certain organs (especially the brain) under conditions such as fasting, but inadequate gluconeogenesis can lead to hypoglycemia and the overproduction of ketone bodies leads to a dangerous state known as ketoacidosis.

Video Ketogenesis

Produksi

Ketone bodies are produced primarily in the mitochondria of liver cells, and synthesis can occur in response to the unavailability of blood glucose, such as during fasting. Other cells are able to do ketogenesis, but they are not effective at doing so. Ketogenesis occurs constantly in healthy individuals.

Ketogenesis occurs in the setting of low glucose levels in the blood, after fatigue from other cell carbohydrate stores, such as glycogen. This can also occur when there is insufficient insulin (eg, type 1 diabetes (but not 2), especially during periods of "ketogenic stress" such as coexisting illness.

The production of the ketone body then begins to make available energy stored as fatty acids. Enzymatic fatty acids are detailed in? -oxidation to form acetyl-CoA. Under normal conditions, acetyl-CoA is more oxidized by the citric acid cycle (TCA/Krebs cycle) and then by the mitochondrial electron transport chain to release energy. However, if the amount of acetyl-CoA produced in fatty acids? -oxidation challenges TCA cycle processing capacity; ie if activity in the TCA cycle is low because of the low intermediate amounts such as oxaloacetate, acetyl-CoA is then used instead of the biosynthesis of the ketone body via acetoacyl-CoA and -hydroxy--s-methylglutaryl-CoA (HMG-CoA). Furthermore, since there are only a limited number of coenzymes A in the liver, the production of ketogenesis allows some conzonymes to be liberated to continue the fatty acids? Oxidation. The depletion of glucose and oxaloacetate can be triggered by rapid, vigorous exercise, high-fat diets or other medical conditions, all of which increase ketone production. Typically degraded amino acids, such as leucine, also feed the TCA cycle, forming acetoacetate & amp; ACoA and therefore produce ketones. In addition to its role in ketone body synthesis, HMG-CoA is also an intermediate in cholesterol synthesis, but the steps are compartmentalized. Ketogenesis occurs in the mitochondria, whereas cholesterol synthesis occurs in the cytosol, so the two processes are regulated independently.

Maps Ketogenesis

Ketone bodies

The three bodies of ketones, each synthesized from the acetyl-CoA molecule, are:

• Acetoacetate, which can be changed by the heart to be? -hydroxybutyrate, or spontaneously changed to acetone
• Acetone, produced by acetoacetate decarboxylation, either spontaneously or via acetoacetate enzyme decarboxylase. It can then be further metabolized either by CYP2E1 to hydroxyacetone (acetol) and then through propylene glycol to pyruvate, lactate and acetate (used for energy) and propionaldehyde, or via methylglyoxal to pyruvate and lactate.
• ? - hydroxybutyrate (not technically a ketone according to the IUPAC nomenclature) is generated through the action of the enzyme D -? - hydroxbutir dehydrogenase in acetoacetate.

? -Hydroxybutyrate is the most abundant of the ketone body, followed by acetoacetate and finally acetone. ? -Hydroxybutyrate and acetoacetate can pass through the membrane easily, and are therefore an energy source for the brain, which can not directly metabolize fatty acids. The brain receives 60-70% of the energy it needs from the body of the ketone when blood glucose levels are low. These bodies are transported to the brain by the monocarboxylate transporters 1 and 2. Therefore, the ketone body is a way to transfer energy from the heart to another cell. The liver does not have an important enzyme, succinyl CoA transferase, to process the ketone body, and therefore can not undergo ketolisis. The result is that the liver produces only ketone bodies, but does not use significant amounts.

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Rule

Ketogenesis may or may not occur, depending on the level of carbohydrates available in the cell or body. This is closely related to the acetyl-CoA pathway:

• When the body has plenty of carbohydrates available as an energy source, glucose is fully oxidized to CO ₂ ; acetyl-CoA is formed as an intermediate in this process, first entering the citric acid cycle followed by the complete conversion of its chemical energy to ATP in oxidative phosphorylation.
• When the body has excess carbohydrates, some glucose is fully metabolized, and some are stored in glycogen or, in excess of citrate, as fatty acids. (CoA is also recycled here.)
• When the body does not have free carbohydrates, the fat should be split into acetyl-CoA to gain energy. Acetyl-CoA is not recycled through the citric acid cycle because the intermediate citric acid cycle (especially oxaloacetate) has been depleted to feed the path of gluconeogenesis, and the accumulation of CoA-akumyl activates ketogenesis.

Insulin and Glucagon are the main regulating hormones of ketogenesis. Both hormones regulate hormone-sensitive lipase and carboxylase acetyl-CoA. Hormone-sensitive lipase produces diglycerides from triglycerides, liberating fatty acid molecules for oxidation. Acetyl-CoA carboxylase catalyzes the production of malonyl-CoA from acetyl-CoA. Malonyl-CoA reduces the activity of carnitine palmitoyltransferase 1, an enzyme that works to bring fatty acids into the mitochondria for? -oxidation. Insulin inhibits hormone-sensitive lipases and activates carboxylase acetyl-CoA, thereby reducing the amount of starting material for fatty acid oxidation and inhibiting their capacity to enter mitochondria. Glucagon activates hormone-sensitive lipases and inhibits acetyl-CoA carboxylases, thus stimulating the production of ketone bodies, and making parts into the mitochondria for? -oxidation is easier. In addition, HMG-CoA lyase is inhibited by insulin, reducing body ketone production. Similarly, cortisol, catecholamines, epinephrine, norepinephrine, and thyroid hormones can increase the number of ketone bodies produced because they increase the concentration of fatty acids available for oxidation.

Peroxisome Proliferator Activated Receptor alpha (PPAR?), Also has the ability to regulate ketogenesis, as it has some control over a number of genes involved in Ketogenesis. For example, Monocarboxylate transporter 1, which is involved in transporting the ketone body through the membrane, is regulated by PPAR ?, thus affecting the transport of the ketone body to the brain. Carnitine palmitoyltransferase is also regulated by PPAR?, Which can affect the transport of fatty acids to mitochondria.

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Pathology

Both acetoacetate and beta-hydroxybutyrate are acidic, and, if these ketone levels are too high, the pH drops blood, resulting in ketoacidosis. Ketoacidosis is known to occur in untreated type I diabetes (see diabetic ketoacidosis) and in alcoholics after prolonged drinking without adequate carbohydrate intake (see alcoholic ketoacidosis).

Ketogenesis can be ineffective in people with beta oxidation defects.

Individuals with diabetes mellitus may experience excess body production of ketones due to lack of insulin. Without insulin to help extract glucose from the blood, the malonyl-CoA level tissue is reduced, and it becomes easier for fatty acids to be transported to the mitochondria, causing excessive acetyl-CoA accumulation. Acetyl-CoA accumulation in turn produces excess ketone bodies through ketogenesis. The result is a higher rate of ketone production, and a decrease in blood pH.

There are several health benefits for ketone bodies and ketogenesis as well. It has been suggested that low-carbohydrate, high-fat ketogenic diets can be used to help treat epilepsy in children. In addition, ketone bodies can be anti-inflammatory. Some types of cancer cells can not use ketone bodies, because they do not have the enzymes needed to engage in ketolisis. It has been proposed that being actively involved in behaviors that promote ketogenesis can help manage the effects of some cancers.

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See also

• Body ketone
• Fatty acid metabolism
• Ketosis
• The ketogenic diet

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References

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External links

• Fat metabolism at the University of South Australia
• James Baggott. (1998) Synthesis and Utilization of Ketones at the University of Utah Retrieved on May 23, 2005.
• Musa-Veloso K, Likhodii SS, Cunnane SC (July 1, 2002). "Acetone Breath is a reliable ketotic indicator in adults who consume ketogenic foods". Am. J. Clin. Nutr . 76 (1): 65-70. PMID 12081817.
• Richard A. Paselk. (2001) Fat Metabolism 2: Ketones Agency at Humboldt State University Obtained May 23, 2005.

Source of the article : Wikipedia