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

Stable Identifier
R-HSA-5694494
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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
7061490 Lipogenesis from ketone bodies in the isolated perfused rat liver. Evidence for the cytosolic activation of acetoacetate

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

J. Biol. Chem. 1982
20102333 Transcriptional regulation of the human acetoacetyl-CoA synthetase gene by PPARgamma

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

Biochem. J. 2010
23396451 Ketone body metabolism and cardiovascular disease

Cotter, DG, Schugar, RC, 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

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

Biochem. Pharmacol. 2003
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
acetoacetate-CoA ligase activity of AACS [cytosol]
Physical Entity
Activity
Orthologous Events
Cross References
Rhea
Authored
Reviewed
Created