Alcohol metabolised in brain, not liver

A paper published in Nature Metabolism has revealed new information about an enzyme in the brain that’s responsible for some of the effects of alcohol intoxication.

Alcohol (or ethanol) does a range of things to the human body. Ethanol blocks and affects some receptors in the brain itself and also turns into other psychoactive molecules through metabolism.

Key research points

  • Acetate is an alcohol metabolite linked to motor impairment.
  • It’s produced by ALDH2, normally seen in the liver.
  • New research finds it in the brain.
  • Removing ALDH2 from mouse brains made the mice more resistant to motor impairment when they consumed alcohol.

This research focused on one of the metabolites from ethanol: acetate. Acetate is partially responsible for some behavioural effects of alcohol intoxication, because it interacts with the inhibitory GABA neurotransmitter. This can affect motor function, among other things.

Acetate is made by an enzyme, called ALDH2. People who experience a ‘blush’ from small amounts of alcohol often have a deficiency of ALDH2, which means they can’t make acetate as quickly and thus end up with a build-up of other metabolites.

The ALDH2 enzyme is abundant in the liver. Acetate can travel from the liver to the brain via the bloodstream and it was thought that this journey was the source of motor impairment from excess alcohol consumption.

But this research showed that ALDH2 is also present in the brain: in cells called astrocytes, which appear in the cerebellum. The researchers examined mouse brains and tissue from human brains and found ALDH2 in the astrocytes of both.

They then examined mice that had been bred to have no ALDH2 in their astrocytes (though they still had some in their livers). The study found that these mice were more resistant to the effects of alcohol consumption, because ALDH2 was not converting alcohol to acetate that accumulated in the brain. Mice without astrocytic ALDH2 also had lower levels of acetate GABA in their brains after consuming alcohol.

The authors conclude that the ALDH2 enzyme has different effects in the liver and in the brain, and they propose further examination of the enzyme in humans. They also suggest that astrocytic ALDH2 could be a useful target for treating alcoholism, and possibly other illnesses.

“Astrocytic ALDH2 is an important target not only for alcohol use disorders but also for other neurological diseases,” concludes the paper.

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