THE CHEMICAL REACTIONS ALLOWING OXIDATION OF ETHANOL TO ACETALDEHYDE
The oxidation of ethanol produces acetaldehyde (see Figure). The production of acetaldehyde by catalase is limited by the availability of hydrogen peroxide, a potentially harmful byproduct of ethanol metabolism by cytochrome P450. Hydrogen peroxide also can come from a number of other sources, including the enzyme monoamine oxidase, ascorbic acid (vitamin C), and other cytochrome P450 oxidations (Sandri et al. 1990; Simonson et al. 1993; Sinet et al. 1980).
Figure Pathways of ethanol metabolism in the brain. The oxidation of ethanol produces acetaldehyde. The production of acetaldehyde by the enzyme catalase (found in internal cell components called peroxisomes) requires hydrogen peroxide (H2O2). The enzyme cytochrome P4502E1 is present in brain cell structures in the smooth endoplasmic reticulum (microsomes). Alcohol dehydrogenase (ADH) is an enzyme found in the cell’s fluid or cytosol. The enzyme aldehyde dehydrogenase (ALDH), found in the cell’s mitochondria and cytosol, converts acetaldehyde to acetate.
All studies of the oxidation of ethanol to acetaldehyde depend on the ability to measure the accumulation of acetaldehyde. This can occur only if the rate of removal of acetaldehyde is slower than its rate of formation in the system under study. Substantial amounts of acetaldehyde are oxidized to acetate in these in vitro systems. This results in an underestimation of the rate of ethanol metabolism in the brain, because acetaldehyde is metabolized to acetate nearly as quickly as it is formed. Thus, only the net amount of acetaldehyde in the system is accounted for when only acetaldehyde accumulation is measured. Studies of the oxidation of ethanol to acetaldehyde in the brain therefore need to consider these limitations.