Most of the ethanol that is consumed is oxidized by the liver using alcohol dehydrogenase (ADH). At the high concentrations associated with chronic alcohol consumption, metabolism of ethanol to acetaldehyde increases while the subsequent conversion into acetate is decreased, leading to even higher levels of acetaldehyde. It was shown in rats that chronic consumption reduced the oxidation of acetaldehyde in the liver, thus providing an explanation for the high blood acetaldehyde levels measured after chronic use in human subjects (Lieber, 1999). Acetaldehyde is toxic and highly reactive (Zakhari, 2006), binding to nearby proteins thus creating an antibody response, decreased DNA repair, and glutathione depletion ultimately reducing the ability of the liver to clear free radicals (Lieber, 1997). As a result from the oxidation, NAD+ is reduced with the addition of an electron to form NADH (Zakhari, 2006) used by mitochondria for ATP synthesis. At high concentrations, ethanol is oxidized by ADH at a higher rate leading to an increase in the NADH/NAD+ ratio (Zakhari, 2006).
