ADH1B is mainly known for its involvement in the major human ethanol metabolic pathway (Figure 4). There are four distinct human ethanol degradation pathways, three oxidative pathways and one non-oxidative pathway [Zakhari 2006]. The oxidative mechanisms differ for the first step where ethanol is converted to acetaldehyde: 1) cytosolic ADH (e.g., ADH1B); 2) Cytochrome P450 2E1 (CYP2E1); 3) Peroxisomal catalase. Acute ethanol consumption induces the hepatic oxidative pathways, predominantly the ADH-mediated pathway [Zakhari 2006]. Conversely, chronic ethanol consumption increases the contribution of hepatic CYP2E1 activity and non-oxidative pathways with respect to ADH. Inhibition of oxidative ethanol metabolism increases FAEE levels, indicating that oxidative and non-oxidative mechanisms are alternative metabolically linked pathways [Zakhari 2006]. In all oxidative pathways, the second step, where acetaldehyde is converted to acetate, is mediated by mitochondrial aldehyde dehydrogenase (ALDH). The non-oxidative metabolism is not completely understood, but its final products are fatty acid ethyl esters (FAEEs) and phosphatidyl ethanol. Ethanol metabolic mechanisms have been observed mainly in hepatic tissue, but also occurs in other organs, including stomach, pancreas, lung, and brain [Deitrich and others 2006; Zakhari 2006].
