Most of the acetate resulting from ethanol metabolism escapes the liver into the blood. In cells with mitochondria that contain enzymes capable of transforming acetate to acetyl CoA, such as heart, skeletal muscle, and brain, the acetate is eventually metabolized to CO2 in the TCA cycle. As shown in figure 3, SIRT1 activates mammalian acetyl-CoA synthase through deacetylation, resulting in the formation of acetyl-CoA. The acetyl-CoA then is used to acetylate histones, resulting in gene activation. Subsequently, SIRT1 deacetylates the histones, resulting in gene silencing. Thus, SIRT1 can act as a sensor to regulate gene transcription.
