Following ethanol oxidation, acetate, the ultimate product of this reaction, produced either locally in the brain or taken up from the circulation after release by the liver, can be readily converted to acetyl-CoA via the acetyl CoA synthetase reaction, joining the tricarboxylic cycle to produce reducing equivalents of NADH and reduced flavin adenine dinucleotide (FADH2; Fig. 1B). These can eventually produce ATP via the oxidative phosphorylation (OXPHOS) reactions (Bowtell et al., 2007), enhancing the cellular [ATP]/[ADP][Pi] energy status of many brain cells, although perhaps not to the levels attained from glucose utilization on a molar basis. Therefore, ethanol can serve as a fuel metabolite directly affecting neuronal energy homeostasis and, directly or indirectly, altering the capacity to revert to glucose utilization.
