Acetyl-CoA synthase and Sir2 may provide a link between the metabolic consequences of ethanol exposure and behavioral response patterns. Unique among the histone deacetylases, the sirtuins require nicotinamide adenine dinucleotide (NAD+) for activity, and therefore are tied to the metabolic state of the cell. Ethanol metabolism leads to decreases in NAD+ levels through the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase (Zakhari, 2006). Lowered NAD+ levels may lead to decreased Sir2 activity, and decreased Sir2 expression levels following ethanol exposure may reflect a means of tuning Sir2 availability to the metabolic state of cells. Additionally, acetyl-CoA, a major product of ethanol metabolism, is the source of acetyl groups for the histone acetyltransferases. The net effect of ethanol metabolism may favor histone acetylation over deacetylation, resulting in increased gene expression following ethanol exposure. Additionally, as noted above, acetyl-CoA is an intermediate for many cellular pathways, including acetylcholine synthesis and the mevalonate pathway. The mevalonate pathway in insects leads to the synthesis of many cellular products, including prenylation that anchors proteins such as the Ras small GTPase family to lipid membranes, and
