Figure 3 |. Intracellular acetate metabolism and the flow of acetate carbons.

Acetate is taken up by the cell through the mechanisms described in FIG. 2. Intracellular acetate is quickly converted into acetyl-CoA by acetyl-CoA synthetase 2 (ACSS2; nucleocytosolic) or ACSS1 (mitochondrial). Cytosolic acetyl-CoA can be used in various biosynthetic pathways, including those that produce fatty acids, isoprenoids and sterols, ketones and N-acetyl-glucosamines (top). Alternatively, acetyl-CoA can be used by lysine acetyltransferases (KATs) to acetylate metabolites and proteins, including histones (bottom right). Conversely, histones, as well as other proteins, and metabolites can be deacetylated by specific lysine deacetylases (KDACs), such as Zn²⁺-containing KDACs (Zn-KDACs), or metabolite deacetylases to regenerate acetate. Mitochondrial acetyl-CoA enters the tricarboxylic acid (TCA) cycle and condenses with oxaloacetate to form citrate (bottom left). Citrate can be further oxidized through the TCA cycle, generating reducing equivalents for ATP production, or citrate can be exported to the cytosol and cleaved back into acetyl-CoA and oxaloacetate. Ac, acetylation; ACCα, acetyl-CoA carboxylase-α; ACLY, ATP citrate lyase; ACOT12, acyl-CoA thioesterase 12; FASN, fatty acid synthase; HMG-CoA, hydroxymethylglutaryl-CoA; HMGCS, hydroxymethylglutaryl-CoA synthase; (S)MCT, (sodium-coupled) monocarboxylate transporter.