 | |
| Names | |
|---|---|
| IUPAC name 3′-O-Phosphonoadenosine 5′-[(3R)-3-hydroxy-2,2-dimethyl-4-oxo-4-{[3-oxo-3-({2-[(3-oxobutanoyl)sulfanyl]ethyl}amino)propyl]amino}butyl dihydrogen diphosphate] | |
| Systematic IUPAC name O1-{[(2R,3S,4R,5R)-5-(6-Amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]methyl}O3-[(3R)-3-hydroxy-2,2-dimethyl-4-oxo-4-{[3-oxo-3-({2-[(3-oxobutanoyl)sulfanyl]ethyl}amino)propyl]amino}butyl] dihydrogen diphosphate | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChemSpider |
|
| ECHA InfoCard | 100.014.378 |
| MeSH | acetoacetyl+CoA |
| |
| |
| Properties | |
| C25H40N7O18P3S | |
| Molar mass | 851.61 g·mol−1 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Acetoacetyl CoA is the precursor ofHMG-CoA in themevalonate pathway, which is essential forcholesterol biosynthesis. It also takes a similar role in theketone bodies synthesis (ketogenesis) pathway of theliver.[1] In the ketone bodies digestion pathway (in the tissue), it is no longer associated with havingHMG-CoA as a product or as a reactant.
It is created fromacetyl-CoA, a thioester, which reacts with theenolate of a second molecule of acetyl-CoA in aClaisen condensation reaction,[2] and it is acted upon byHMG-CoA synthase to formHMG-CoA.[1] During the metabolism ofleucine, this last reaction is reversed. Some individuals may experience Acetoacetyl-CoA deficiency.[3] This deficiency is classified as a disorder ketone body and isoleucine metabolism that can be inherited.[citation needed] Additional mutations include those with the enzymes within pathways related to Acetoacetyl CoA, including Beta-Ketothiolase deficiency and Mitochondrial 3-hydroxy-3-methylglutaryl-CoA Synthase mutation.
Additionally, it reacts with NADPH-dependent acetoacetyl-coenzyme A reductase, also known as PhaB, in a pathway that produces polyester polyhydroxyalkanoate (PHA). The reduction of acetoacetyl-coA by Pha creates (R)-3-hydroxybutyryl-CoA, which polymerizes to PHA.[4] The pathway is present in bacteria such as Ralstonia eutropha and the PCC6803 strain ofSynechocystis.[5] Mover over, Acetoacetyl-CoA is involved with neuronal development involvinglipogenesis and providing fats and cholesterol for neuronal cells.
Mitochondrialacetoacetyl-CoA thiolase, also known as thiolase II, the enzyme responsible for catalyzing the synthesis of acetoacetyl-CoA within ketogenesis as mentioned, is also involved within acetoacetyl-CoA cleavage in ketolysis. It is observed to play a role within cleavage of acetyl-CoA from acetoacetyl-CoA and 2-methylacetoacetyl-CoA. The enzyme is involved in an autosomal recessive disorders that impacts the catabolism of ketone bodies and isoleucine:beta-ketothiolase deficiency, leading to their deficiency within mitochondria. The mutation takes place within the acetoacetyl-CoA thiolase (ACAT) gene mapped on chromosome 11q22.3-23.1.[6]
Mutations in mitochondrial3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) is another inherited autosomal recessive disorder affecting the catabolism of ketone bodies and can lead to the build-up of acetoacetyl-CoA.[7]
Acetoacetyl-CoA also behaves as a product ofacetoacetyl-CoA synthetase (AACS) within the cytosol, using acetoacetate as the substrate, the reaction provides acetyl groups forlipogenesis.[8] Understanding acetoacetyl-CoA is important in cholesterol development and lipogenesis and Acetoacetyl-CoA synthetase playing a role in its development, it also plays a significant role within the brain. Cholesterol and fats have been observed in high concentrations withinneuronal tissue, as well as high AACS mRNA expression levels within cells of thehippocampus andcortical region. In addition, they play a significant role in neuronal development during the early embryonic and fetal developmental stages.[9]
