AACS ligates CoA-SH to ACA, forming ACA-CoA

Stable Identifier
Homo sapiens
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Ketone bodies (KBs) are an energy source utilised by mammals, the terminal oxidation of which (termed ketogenesis) is most active during fasting states or starvation. This process normally occurs in the mitochondria of cells. Cytoplasmic de novo lipogenesis and cholesterol synthesis are nonoxidative metabolic fates of ketone bodies. Acetoacetyl-CoA synthetase (AACS) mediates the activation of acetoacetate (ACA) to the KB acetoacetyl-CoA (ACA-CoA) in the cytosol of cells of lipogenic tissues (Aquilo et al. 2010). AACS is proposed to provide an alternative supply of acetyl units from that of mitochondrial ketogenesis for de novo lipogenesis and cholesterol synthesis in the brain, based on rat experiments (Endemann et al. 1982, review Cotter et al. 2013). Human AACS mRNA is abundant in the kidney, heart and brain, but low in liver (Ohgami et al. 2003).

Literature References
PubMed ID Title Journal Year
20102333 Transcriptional regulation of the human acetoacetyl-CoA synthetase gene by PPARgamma

Aguiló, F, Camarero, N, Haro, D, Marrero, PF, Relat, J

Biochem. J. 2010
7061490 Lipogenesis from ketone bodies in the isolated perfused rat liver. Evidence for the cytosolic activation of acetoacetate

Endemann, G, Brunengraber, H, Edmond, J, Goetz, PG

J. Biol. Chem. 1982
23396451 Ketone body metabolism and cardiovascular disease

Schugar, RC, Cotter, DG, Crawford, PA

Am. J. Physiol. Heart Circ. Physiol. 2013
12623130 Expression of acetoacetyl-CoA synthetase, a novel cytosolic ketone body-utilizing enzyme, in human brain

Takahashi, N, Fukui, T, Yamasaki, M, Ohgami, M

Biochem. Pharmacol. 2003
Catalyst Activity

acetoacetate-CoA ligase activity of AACS [cytosol]

Orthologous Events
Cross References
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