Metabolic Pathways of Toxic Alcohols Panel A shows the metabolic pathways of toxic alcohols. Alcohol dehydrogenase and aldehyde dehydrogenase sequentially oxidize the toxic alcohols. Alcohol dehydrogenase catalyzes the first oxidation of the toxic alcohols and is an important target for antidotal therapy. The enclosed boxes highlight the putative toxic metabolites. Methanol is metabolized to formic acid, ethylene glycol to oxalic and glycolic acid, diethylene glycol to 2.hydroxyethoxyacetic acid and glycolic acid, and propylene glycol to D-lactic and L-lactic acid. Panel B shows the time course of changes in the osmolal and anion gaps with and without coingested ethanol. An increased osmolal gap is prominent early owing to the accumulation of the un.ionized alcohols. As metabolism proceeds, the osmolal gap declines with the formation of ionized metabolites. Conversely, the serum anion gap is lowest before the alcohol is metabolized and increases with the formation of ionized metabolites. The time course of these changes in both parameters varies among the alcohols. They typically evolve over several hours to over a day. Coingested ethanol impedes metabolism (dashed lines) and delays the onset of the high anion-gap acidosis. #Pathophysiology #Toxicology #ToxicAlcohols #Metabolism #Pathways #Osmolar #OsmolalGap #AnionGap #Timeline #NEJM
