Over 90% of alcohol consumed is oxidized in the liver; much of the remainder is excreted through the lungs and in the urine.
Two major pathways of alcohol metabolism to acetaldehyde have been identified.
Acetaldehyde is then oxidized by a third metabolic process.
Figure: Metabolism of ethanol by alcohol dehydrogenase and the microsomal ethanol-oxidizing system (MEOS).
Alcohol dehydrogenase and aldehyde dehydrogenase are inhibited by fomepizole and disulfiram, respectively.
The primary pathway for alcohol metabolism involves alcohol dehydrogenase (ADH), a cytosolic enzyme that catalyzes the conversion of alcohol to acetaldehyde. This enzyme is located mainly in the liver, but it is also found in other organs such as brain and stomach.
During conversion of ethanol to acetaldehyde, hydrogen ion is transferred from alcohol to the
cofactor nicotinamide adenine dinucleotide (NAD+) to form NADH. As a net result, alcohol
oxidation generates an excess of reducing equivalents in the liver, chiefly as NADH.
Another pathway is the Microsomal Ethanol Oxidizing System (MEOS). It uses NADPH as a cofactor in the metabolism of ethanol.
At blood concentrations below 100 mg/dL (22 mmol/L), the MEOS system, which has a relatively high Km for alcohol, contributes little to the metabolism of ethanol. However, when large amounts of ethanol are consumed, the alcohol dehydrogenase system becomes saturated owing to depletion of the required cofactor, NAD+. As the concentration of ethanol increases above 100 mg/dL, there is increased contribution from the MEOS system, which does not rely upon NAD+ as a cofactor.
During chronic alcohol consumption, MEOS activity increases. As a result, chronic alcohol
consumption results in significant increases not only in ethanol metabolism but also in the clearance of other drugs eliminated by the MEOS system.
Much of the acetaldehyde formed from alcohol appears to be oxidized in the liver in a reaction
catalyzed by mitochondrial NAD-dependent aldehyde dehydrogenase. The product of this reaction is acetate which can be further metabolized to CO2 and water.
Lavoro svolto da Alessandro Malatesta ed Emanuele Turbil