As a possible compensatory response to reduced glucose utilization capacity due to chronic ethanol exposure, monocarboxylate transporters for lactate uptake are induced in neurons (Lindberg et al., 2019). Lactate is a metabolic dead-end; lactate carbons only become useful to support cellular fuel metabolism when they are converted to pyruvate via lactate dehydrogenase in the presence of cytosolic NAD+ (Brooks, 2020). In selected populations of neurons that express Class I alcohol dehydrogenase (ADH) (Wang et al., 2019, Martinez et al., 2001), cytosolic NAD+ is likely exhausted for the conversion of ethanol to acetaldehyde (Hoog and Ostberg, 2011), thereby diminishing the utilization of lactate for the astrocyte-neuron lactate shuttle (Lindberg et al., 2019). This, together with reduced glycolytic capacities, ultimately alters the neuronal lactate/pyruvate ratio (Wright and Marks, 1984).
