BACKGROUND Acetyl-CoA synthetase (AceCS, EC 184.108.40.206) catalyzes the ligation of acetate with CoA to produce acetyl-CoA, an essential molecule utilized in various metabolic pathways. These pathways include fatty acid and cholesterol synthesis and the tricarboxylic acid cycle.1 The activity of the enzyme is controlled in several ways. The essential lysine residue (Lys642 in human) in the active site plays an important role in regulation of activity. The lysine molecule can be deacetylated by another class of enzyme called sirtuins, more specifically Sirt3.2
In addition to sirtuins, protein deacetylase (AcuC) can also modify acetyl-CoA at a lysine residue. While acetyl-CoA synthetase’s activity is usually associated with metabolic pathways, the enzyme also participates in regulating gene expression. In yeast, acetyl-CoA synthetase delivers acetyl-CoA to histone acetyltransferases for histone acetylation. Without correct acetylation, DNA cannot condense into chromatin properly, which inevitably results in transcriptional errors.3 Acetyl-CoA synthetase also participates in the Wood-Ljungdahl Pathway, which fixes anaerobic CO2.4
1. Starai VJ & Escalante-Semerena JC: Cell Mol Life Sci. 61:2020-30, 2004.
2. North BJ & Sinclair DA: Trends Biochem Sci. 32:1-4, 2007.
3. Takahashi H. et al.: Mol Cell. 23:207-17, 2006.
4. Hegg EL: Acc Chem. Res. 37:775-83, 2004.
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