The importance of acetaldehydein the metabolism and mechanismof ethyl alcohol action

Acetaldehyde is the first metabolite of ethanol and may be formed by alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1) and catalase. ADH is an essential pathway that oxidises alcohol in peripheral tissues (primarily in the liver).

Acetaldehyde is oxidised to acetic acid by the aldehyde dehydrogenase (ALDH) enzyme. Acetaldehyde passes into the brain from the peripheral blood with difficulty, due to the blood-brain metabolic barrier, which is ALDH in the brain blood vessels. Acetaldehyde can be formed directly in the brain, mainly by catalase enzyme. Another important enzyme metabolising ethanol in central nervous system is CYP2E1.

The gene mutation (ALDH2*2) causes an increase in the level of acetaldehyde in the blood during alcohol drinking. Increased level of acetaldehyde in the peripheral blood may clearly protect against alcohol abuse by producing severe adverse effects (tachycardia, headache, facial flushing, nausea). Central acetaldehyde may be responsible for alcohol-enhancing effects that support alcohol consumption.

Anxiolytic alcohol properties are associated with the action of acetaldehyde. Acetaldehyde also has depressive properties on locomotor activity after peripheral administration, while it has a stimulating effect after administration to the brain.

The reinforcement properties of acetaldehyde are the effect of dopamine release in the nucleus accumbens and other structures of the limbic and the reward systems.

The International Agency for Research on Cancer has identified acetaldehyde as the 1st carcinogenic group of the esophagus and/or head and neck.