Ketogenesis 299619 220546629 2008-06-20T11:33:48Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. [[Image:Ketogenesis.png|thumb|300px|right|Ketogenesis Pathway]] '''Ketogenesis''' is the process by which [[ketone bodies]] are produced as a result of [[fatty acid metabolism|fatty acid breakdown]]. ==Production== Ketone bodies are produced mainly in the [[mitochondria]] of [[liver]] cells. Its synthesis occurs in response to low [[carbohydrate]] levels in the blood, and after exhaustion of cellular carbohydrate stores, such as [[glycogen]]. The production of ketone bodies is then initiated to make available energy that is stored as [[fatty acid]]s. Fatty acids are enzymatically broken down in [[β-oxidation]] to form [[acetyl-CoA]]. Normally, acetyl-CoA is further oxidized and its energy transferred as electrons to [[NADH]], [[FADH2|FADH<sub>2</sub>]], and [[GTP]] 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]]). Besides its role in the synthesis of ketone bodies, HMG-CoA is also an intermediate in the synthesis of [[cholesterol]]. ==Types of ketone bodies== The three ketone bodies are: * [[Acetoacetate]]; if not oxidized to form usable energy, it is the source of the two other ketone bodies below. * [[Acetone]]; is not used as an energy source, but is instead exhaled or excreted as waste. * [[Beta-hydroxybutyrate|β-hydroxybutyrate]]; it is not technically a [[ketone]] according to [[IUPAC]] nomenclature. Each of these compounds are synthesized from acetyl-CoA molecules. ==Regulation== Ketogenesis may or may not occur, depending on levels of available carbohydrates in the cell or body. This is closely related to the paths of acetyl-CoA: * When the body has ample carbohydrates available as energy source, [[glucose]] is completely oxidized to [[carbon dioxide|CO<sub>2</sub>]]; acetyl-CoA is formed as an intermediate in this process, first entering the [[citric acid cycle]] followed by complete conversion of its chemical energy to [[Adenosine triphosphate|ATP]] in [[electron transfer chain|oxidative phosporylation]]. * When the body has excess carbohydrates available, some glucose is fully metabolized, and some of it is stored by using acetyl-CoA to create [[fatty acids]]. (CoA is also recycled here.) * When the body has no free carbohydrates available, fat must be broken down into acetyl-CoA in order to get energy. Acetyl-CoA is not being recycled through the citric acid cycle because the citric acid cycle intermediates (mainly oxaloacetate) have been depleted to feed the [[gluconeogenesis]] pathway, and the resulting accumulation of acetyl-CoA activates ketogenesis. ==Pathology== Ketone bodies are created at moderate levels in everyone's bodies, such as during sleep and other times when no carbohydrates are available. However, when ketogenesis is happening at higher than normal levels, the body is said to be in a state of [[ketosis]]. It is unknown whether ketosis has negative long-term effects or not. Both acetoacetate and beta-hydroxybutyrate are [[acid|acidic]], and, if levels of these ketone bodies are too high, the [[pH]] of the blood drops, resulting in [[ketoacidosis]]. This is very rare, and, in general, happens only in untreated Type I [[diabetes]] (see [[diabetic ketoacidosis]]) and in [[alcoholic]]s after binge drinking and subsequent starvation (see [[alcoholic ketoacidosis]]). ==See also== * [[ketone bodies]] * [[fatty acid metabolism]] * [[Ketosis]] ==External links== * [http://www.unisanet.unisa.edu.au/08366/h&p2fat.htm Fat metabolism] at [[University of South Australia]] * James Baggott. (1998) [http://www-medlib.med.utah.edu/NetBiochem/FattyAcids/10_1.html Synthesis and Utilization of Ketone Bodies] at [[University of Utah]] Retrieved 23 May 2005. * {{cite journal |author=Musa-Veloso K, Likhodii SS, Cunnane SC |title=Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals |journal=Am. J. Clin. Nutr. |volume=76 |issue=1 |pages=65–70 |year=2002 |pmid=12081817 |url=http://www.ajcn.org/cgi/content/full/76/1/65}} * Richard A. Paselk. (2001) [http://www.humboldt.edu/~rap1/C431.F01/C431Notes/C431n07Dec.htm Fat Metabolism 2: Ketone Bodies] at [[Humboldt State University]] Retrieved 23 May 2005. {{Lipid metabolism enzymes}} [[Category:Metabolism]] [[de:Ketogenese]] [[fr:Cétogenèse]] [[sv:ketogenes]] [[es:Cetogénesis]]