Editing Ketone bodies (section)

==Production==
[[Image:Acetyl-CoA-2D colored.svg|thumb|300 px|[[Acetyl-CoA]] with the [[Acetyl|acetyl group]] indicated in blue.]]
Fats stored in [[adipose tissue]] are released from the [[Adipocytes|fat cells]] into the blood as [[free fatty acids]] and [[glycerol]] when [[insulin]] levels are low and [[glucagon]] and [[epinephrine]] levels in the blood are high. This occurs between meals, during fasting, starvation and strenuous exercise, when [[blood sugar level|blood glucose levels]] are likely to fall. Fatty acids are very high energy fuels and are taken up by all metabolizing cells that have [[mitochondria]]. This is because fatty acids can only be metabolized in the mitochondria.<ref name=stryer2 /><ref name="oxidation_of_fats">{{Cite web |url=http://pharmaxchange.info/press/2013/10/oxidation-of-fatty-acids/ |title=Oxidation of fatty acids |date=11 October 2013 |access-date=2015-12-17 |archive-date=2018-01-08 |archive-url=https://web.archive.org/web/20180108172703/http://pharmaxchange.info/press/2013/10/oxidation-of-fatty-acids/ |url-status=live }}</ref> [[Erythrocytes|Red blood cells]] do not contain mitochondria and are therefore entirely dependent on [[anaerobic glycolysis]] for their energy requirements. In all other tissues, the fatty acids that enter the metabolizing cells are combined with [[coenzyme A]] to form [[acyl-CoA]] chains. These are transferred into the mitochondria of the cells, where they are broken down into acetyl-CoA units by a sequence of reactions known as [[Beta-oxidation|β-oxidation]].<ref name=stryer2 /><ref name="oxidation_of_fats" />

The acetyl-CoA produced by β-oxidation enters the citric acid cycle in the mitochondrion by combining with [[Oxaloacetic acid|oxaloacetate]] to form [[citric acid|citrate]]. This results in the complete combustion of the acetyl group of acetyl-CoA (see diagram above, on the right) to CO<sub>2</sub> and water. The energy released in this process is captured in the form of 1 [[Guanosine triphosphate|GTP]] and 9 [[Adenosine triphosphate|ATP]] molecules per acetyl group (or [[acetic acid]] molecule) oxidized.<ref name=stryer2 /><ref name="oxidation_of_fats" /> This is the fate of acetyl-CoA wherever β-oxidation of fatty acids occurs, except under certain circumstances in the [[liver]]. In the liver oxaloacetate is wholly or partially diverted into the [[gluconeogenesis|gluconeogenic pathway]] during fasting, starvation, a low carbohydrate diet, prolonged strenuous exercise, and in uncontrolled [[Diabetes mellitus#Type 1|type 1 diabetes mellitus]]. Under these circumstances oxaloacetate is hydrogenated to [[Malic acid|malate]] which is then removed from the mitochondrion to be converted into glucose in the [[cytoplasm]] of the liver cells, from where the glucose is released into the blood.<ref name=stryer2 /> In the liver, therefore, oxaloacetate is unavailable for condensation with acetyl-CoA when significant gluconeogenesis has been stimulated by low (or absent) insulin and high [[glucagon]] concentrations in the blood. Under these circumstances, acetyl-CoA is diverted to the formation of acetoacetate and beta-hydroxybutyrate.<ref name=stryer2 /> Acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone,<ref>[http://watcut.uwaterloo.ca/webnotes/Metabolism/fatKetoneBodyMetabolism.html Ketone body metabolism] {{Webarchive|url=https://web.archive.org/web/20160922094349/http://watcut.uwaterloo.ca/webnotes/Metabolism/fatKetoneBodyMetabolism.html |date=2016-09-22 }}, University of Waterloo</ref> are known as ketone bodies. The ketone bodies are released by the liver into the blood. All cells with mitochondria can take ketone bodies up 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 the liver does this. Unlike free fatty acids, ketone bodies can cross the [[blood–brain barrier]] and are therefore available as fuel for the cells of the [[central nervous system]], acting as a substitute for glucose, on which these cells normally survive.<ref name=stryer2 /> The occurrence of high levels of ketone bodies in the blood during starvation, a low carbohydrate diet and prolonged heavy exercise can lead to ketosis, and in its extreme form in out-of-control type 1 diabetes mellitus, as [[ketoacidosis]].

Acetoacetate has a highly characteristic smell, for the people who can detect this smell, which occurs in the breath and urine during ketosis. On the other hand, most people can smell acetone, whose "sweet & fruity" odor also characterizes the breath of persons in ketosis or, especially, ketoacidosis.<ref>{{Cite web |url=http://www.diabetes.org/living-with-diabetes/complications/ketoacidosis-dka.html |title=American Diabetes Association-Ketoacidosis |access-date=2010-03-02 |archive-date=2010-04-29 |archive-url=https://web.archive.org/web/20100429123055/http://www.diabetes.org/living-with-diabetes/complications/ketoacidosis-dka.html |url-status=dead }}</ref>