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==Biochemistry== Under typical physiological conditions, acetoacetic acid exists as its [[conjugate base]], '''acetoacetate''': :{{chem2|[[Acetyl|Ac]]CH2CO2H -> AcCH2CO2- + H+}} Unbound acetoacetate is primarily produced by [[liver]] [[mitochondria]] from its [[thioester]] with [[coenzyme A]] (CoA): :{{chem2|AcCH2C(O)\sCoA + OH- -> AcCH2CO2- + H\sCoA}} The [[acetoacetyl-CoA]] itself is formed by three routes: *[[HMG-CoA|3-hydroxy-3-methylglutaryl CoA]] releases acetyl CoA and acetoacetate: *:{{chem2|-O2CCH2\sC([[Methyl|Me]])(OH)\sCH2C(O)\sCoA -> -O2CCH2\sAc + Ac\sCoA}} *Acetoacetyl-CoA can come from [[beta oxidation]] of [[butyryl-CoA]]: *:{{chem2|[[Et]]\sCH2C(O)\sCoA + 2NAD+ + H2O + FAD -> Ac\sCH2C(O)\sCoA + 2NADH + FADH2}} *Condensation of pair of acetyl CoA molecules as catalyzed by [[thiolase]].<ref name=Stryer1981>{{cite book|author=Lubert Stryer|author-link=Lubert Stryer|title=Biochemistry|date=1981 |edition=2nd|title-link=Biochemistry (Stryer)}}</ref>{{rp|393}} *:{{chem2|2Ac\sCoA -> AcCH2C(O)\sCoA + H\sCoA}} In mammals, acetoacetate produced in the liver (along with the other two "[[ketone bodies]]") is released into the bloodstream as an energy source during periods of [[fasting]], exercise, or as a result of [[type 1 diabetes mellitus]].<ref name=stryer2>{{cite book |last1= Stryer |first1= Lubert | title=Biochemistry. | edition= Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages= 510β515, 581β613, 775β778 |isbn= 0-7167-2009-4 }}</ref> First, a CoA group is enzymatically transferred to it from [[succinyl CoA]], converting it back to acetoacetyl CoA; this is then broken into two acetyl CoA molecules by thiolase, and these then enter the [[citric acid cycle]]. Heart muscle and renal cortex prefer acetoacetate over glucose. The brain uses acetoacetate when glucose levels are low due to fasting or diabetes.<ref name=Stryer1981/>{{rp|394}}
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