Most brain cells are able to produce acetaldehyde via any one of these three pathways (Bowtell et al., 2007). Early immunohistochemical studies indicated that these enzymes are detected in different brain regions in both neurons and glia (Zimatkin and Deitrich, 1997, Kerr et al., 1989), with CAT- and CYP2E1-mediated reactions dominating, and the ADH reaction playing only a minor role (Zimatkin and Deitrich, 1997). While ADH can be detected immunocytochemically in brain (Buhler et al., 1983), activity studies conclude that the dominant class of enzyme in brain is the low-affinity Class III ADH, which is likely to be ineffective at ethanol concentrations found in tissues (Giri et al., 1989). Ethanol metabolized in astrocytes has been reported by others (Jin et al., 2021a, Fonseca et al., 2001), and studies have shown that astrocyte metabolism also underlies behavioral effects of ethanol (Jin et al., 2021a, Jin et al., 2021b), but we will focus here on its metabolism in neurons. Recent results from Sun and colleagues (Sun et al., 2023) agree with previous findings (Howard et al., 2003), that CYP2E1 is uniquely induced in pyramidal neurons of the prefrontal cortex upon chronic ethanol exposure.
