Acetoacetyl-CoA

Acetoacetyl-CoA
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 Edit this at Wikidata
MeSH acetoacetyl+CoA
  • InChI=1S/C25H40N7O18P3S/c1-13(33)8-16(35)54-7-6-27-15(34)4-5-28-23(38)20(37)25(2,3)10-47-53(44,45)50-52(42,43)46-9-14-19(49-51(39,40)41)18(36)24(48-14)32-12-31-17-21(26)29-11-30-22(17)32/h11-12,14,18-20,24,36-37H,4-10H2,1-3H3,(H,27,34)(H,28,38)(H,42,43)(H,44,45)(H2,26,29,30)(H2,39,40,41)/t14-,18-,19-,20+,24-/m1/s1 checkY
    Key: OJFDKHTZOUZBOS-CITAKDKDSA-N checkY
  • InChI=1/C25H40N7O18P3S/c1-13(33)8-16(35)54-7-6-27-15(34)4-5-28-23(38)20(37)25(2,3)10-47-53(44,45)50-52(42,43)46-9-14-19(49-51(39,40)41)18(36)24(48-14)32-12-31-17-21(26)29-11-30-22(17)32/h11-12,14,18-20,24,36-37H,4-10H2,1-3H3,(H,27,34)(H,28,38)(H,42,43)(H,44,45)(H2,26,29,30)(H2,39,40,41)/t14-,18-,19-,20+,24-/m1/s1
    Key: OJFDKHTZOUZBOS-CITAKDKDBD
  • O=C(C)CC(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n2cnc1c(ncnc12)N)[C@H](O)[C@@H]3OP(=O)(O)O
Properties
C25H40N7O18P3S
Molar mass 851.61 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Acetoacetyl CoA is the precursor of HMG-CoA in the mevalonate pathway, which is essential for cholesterol biosynthesis. It also takes a similar role in the ketone bodies synthesis (ketogenesis) pathway of the liver.[1] In the ketone bodies digestion pathway (in the tissue), it is no longer associated with having HMG-CoA as a product or as a reactant.

It is created from acetyl-CoA, a thioester, which reacts with the enolate of a second molecule of acetyl-CoA in a Claisen condensation reaction,[2] and it is acted upon by HMG-CoA synthase to form HMG-CoA.[1] During the metabolism of leucine, 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.

Mevalonate pathway
Mevalonate pathway

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 of Synechocystis.[5] Mover over, Acetoacetyl-CoA is involved with neuronal development involving lipogenesis and providing fats and cholesterol for neuronal cells.

  1. ^ a b Hasegawa, Shinya; Noda, Kazuki; Maeda, Akina; Matsuoka, Masaru; Yamasaki, Masahiro; Fukui, Tetsuya (2012-11-01). "Acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, is controlled by SREBP-2 and affects serum cholesterol levels". Molecular Genetics and Metabolism. 107 (3): 553–560. doi:10.1016/j.ymgme.2012.08.017. ISSN 1096-7192. PMID 22985732.
  2. ^ Bruice PY (2017). Organic chemistry. Pearson. ISBN 978-0-13-404228-2. OCLC 974910578.
  3. ^ Tsuda H, Shiraki M, Inoue E, Saito T (August 2016). "Generation of poly-β-hydroxybutyrate from acetate in higher plants: Detection of acetoacetyl CoA reductase- and PHB synthase- activities in rice". Journal of Plant Physiology. 201: 9–16. Bibcode:2016JPPhy.201....9T. doi:10.1016/j.jplph.2016.06.007. PMID 27372278.
  4. ^ Matsumoto K, Tanaka Y, Watanabe T, Motohashi R, Ikeda K, Tobitani K, et al. (October 2013). "Directed evolution and structural analysis of NADPH-dependent Acetoacetyl Coenzyme A (Acetoacetyl-CoA) reductase from Ralstonia eutropha reveals two mutations responsible for enhanced kinetics". Applied and Environmental Microbiology. 79 (19): 6134–6139. Bibcode:2013ApEnM..79.6134M. doi:10.1128/aem.01768-13. PMC 3811355. PMID 23913421.
  5. ^ Taroncher-Oldenburg G, Nishina K, Stephanopoulos G (October 2000). "Identification and analysis of the polyhydroxyalkanoate-specific beta-ketothiolase and acetoacetyl coenzyme A reductase genes in the cyanobacterium Synechocystis sp. strain PCC6803". Applied and Environmental Microbiology. 66 (10): 4440–4448. Bibcode:2000ApEnM..66.4440T. doi:10.1128/aem.66.10.4440-4448.2000. PMC 92322. PMID 11010896.