Alcohol Affects Most Organs; More Than a Liver Problem

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Alcohol Affects Most Organs

How alcohol damages the liver has been well understood for more than a decade, but its insidious harm to other organs has long perplexed medical scientists.

Now researchers at Washington University School of Medicine in St. Louis, Missouri, have evidence that a newly discovered biochemical pathway operates in organs susceptible to alcohol damage. The pathway joins alcohol to fatty acids, forming a toxin that differs from the one made from alcohol in the liver.

This discovery - described recently in the journal Science - provides the first viable explanation of how organs other than the liver sustain damage from alcohol. And it has practical implications. Detection of the toxin could help forensic scientists identify alcohol use in victims of accidents and child abuse. Studies of the pathway's pattern of inheritance may also shed light on the genetic basis of alcoholism.

Current theories about the destructive effects of alcohol metabolism focus on a compound called acetaldehyde, which is made in the liver from ethyl alcohol and reaches other organs only in minute amounts.

"Our discovery points to the fact that there have to be other agents involved.," says Louis Lange, M.D., Ph.D., the study's principal investigator. "You can't find a way for acetaldehyde, produced primarily in the liver, to explain why one alcoholic has pancreatic damage but no brain damage, or why another has heart damage but nothing in the pancreas. Applying current theory of how alcohol is metabolized in the liver and produces injury just can't explain it. Something in an organ must make it selectively susceptible to damage."

In the early 1980s, Lange, associate professor in medicine and pathology, looked at the fate of alcohol in susceptible organs. He made the intriguing observation that heart muscle cells metabolize alcohol by combining it with fatty acids to form substances called esters. He also purified the responsible enzyme - which turned out to be a relative of the enzyme that makes esters from fatty acids and a more complex alcohol - cholesterol.

He also found that concentrations of the esters in the pancreas, brain, liver, heart, and body fat were significantly higher in persons who died while acutely intoxicated than in persons who died with no alcohol in the blood or history of drinking. …