Among individuals who have alcohol dependence, the contribution of ethanol carbons to daily caloric intake could be as high as 50% or more (Dettling et al., 2007, Bach et al., 2019). As a negative feedback to this additional carbon input, downregulation in metabolic flux of physiological metabolites is observed, particularly the glucose metabolism in the brain (Volkow et al., 2013, Volkow et al., 2006, Volkow et al., 2015, Wang et al., 2000). The commitment step of glucose carbons into glycolysis is catalysed by phosphofructokinase-1 (PFK1) (Kanai et al., 2019), an allosteric enzyme controlled by various activators and inhibitors. The high intracellular [ATP]/[ADP] ratio — a condition immediately induced by ethanol oxidation — is known to inhibit this kinase, therefore inhibiting glycolytic flux, further reinforcing the use of ethanol-derived carbons (Fig. 1C) (Stine and Dang, 2013, Brüser et al., 2012).
