Editing Ketosis (section)

==Biochemistry==
The precursors of ketone bodies include fatty acids from [[adipose tissue]] or the diet and [[ketogenic amino acids]].<ref name=":0">{{cite journal | vauthors = Coelho M, Oliveira T, Fernandes R | title = Biochemistry of adipose tissue: an endocrine organ | journal = Archives of Medical Science | volume = 9 | issue = 2 | pages = 191–200 | date = 2013 | pmid = 23671428 | pmc = 3648822 | doi = 10.5114/aoms.2013.33181}}</ref><ref name=":1">{{Cite book|title=Nutrient metabolism : structures, functions, and genes|last=Kohlmeier|first=Martin|isbn=978-0-12-387784-0|oclc=913852019|date = 2015-05-22|publisher=Elsevier Science }}</ref> The formation of ketone bodies occurs via [[ketogenesis]] in the [[Mitochondrion|mitochondrial]] matrix of liver cells.

Fatty acids can be released from adipose tissue by [[adipokine]] signaling of high [[glucagon]] and [[epinephrine]] levels and low insulin levels. High glucagon and low insulin correspond to times of low glucose availability such as fasting.<ref>{{cite journal |last1=Owen |first1=Oliver E. |title=Ketone bodies as a fuel for the brain during starvation |journal=Biochemistry and Molecular Biology Education |date=July 2005 |volume=33 |issue=4 |pages=246–251 |doi=10.1002/bmb.2005.49403304246 |s2cid=11278861 |doi-access=free }}</ref> Fatty acids bound to [[coenzyme A]] allow penetration into mitochondria. Once inside the mitochondrion, the bound fatty acids are used as fuel in cells predominantly through [[beta oxidation]], which cleaves two carbons from the acyl-CoA molecule in every cycle to form [[acetyl-CoA]]. Acetyl-CoA enters the [[citric acid cycle]], where it undergoes an [[aldol condensation]] with [[Oxaloacetic acid|oxaloacetate]] to form [[citric acid]]; citric acid then enters the [[tricarboxylic acid cycle]] (TCA), which harvests a very high energy yield per carbon in the original fatty acid.<ref name="stryer32">{{cite book |title=Biochemistry |publisher=W.H. Freeman and Company |isbn=0-7167-2009-4 |edition=Fourth |location=New York|date=1995|pages=510–515, 581–613, 775–778 |last1=Stryer |first1=Lubert }}</ref>
[[File:Ketones.svg|right|frameless|420x420px|Biochemical pathway of ketone synthesis in the liver and utilization by organs]]
Acetyl-CoA can be metabolized through the TCA cycle in any cell, but it can also undergo ketogenesis in the mitochondria of liver cells.<ref name=":6">{{cite journal |last1=Laffel |first1=Lori |title=Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes |journal=Diabetes/Metabolism Research and Reviews |date=November 1999 |volume=15 |issue=6 |pages=412–426 |doi=10.1002/(SICI)1520-7560(199911/12)15:6<412::AID-DMRR72>3.0.CO;2-8 |pmid=10634967 |doi-access=free }}</ref> When glucose availability is low, oxaloacetate is diverted away from the TCA cycle and is instead used to produce glucose via [[gluconeogenesis]]. 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]]. Acetoacetyl-CoA briefly combines with another acetyl-CoA via [[Hydroxymethylglutaryl-CoA synthase|HMG-CoA synthase]] to form [[HMG-CoA|hydroxy-β-methylglutaryl-CoA]]. Hydroxy-β-methylglutaryl-CoA form the ketone body acetoacetate via [[3-hydroxy-3-methylglutaryl-CoA lyase|HMG-CoA lyase]]. Acetoacetate can then reversibly convert to another ketone body—[[D-β-hydroxybutyrate]]—via D-β-hydroxybutyrate dehydrogenase. Alternatively, acetoacetate can spontaneously degrade to a third ketone body (acetone) and [[carbon dioxide]], which generates much greater concentrations of acetoacetate and D-β-hydroxybutyrate. The resulting ketone bodies cannot be used for energy by the liver so are exported from the liver to supply energy to the brain and peripheral tissues.

In addition to fatty acids, deaminated [[ketogenic amino acids]] can also be converted into intermediates in the citric acid cycle and produce ketone bodies.<ref name=":1" />