Oxidation of ethanol in the brain and its consequences

Abstract

Acetaldehyde, a toxic byproduct of alcohol (i.e., ethanol) metabolism, has long been suspected of causing at least some of the central nervous system actions of ethanol. However, the data to support such a hypothesis have been difficult to obtain. One roadblock is the very low blood levels of acetaldehyde following ethanol intake and the finding that even elevated acetaldehyde levels in the blood do not easily gain access to the brain. The recent discovery of the oxidation of ethanol to acetaldehyde in the adult brain may help explain the acute effects of ethanol.

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.