Alcohol affects most organs; more than a liver problem.
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.
Moreover, the ester concentrations mirrored the levels of blood alcohol. Chronic alcoholics with no alcohol in the blood at death also had high concentrations of esters - but only in body fat. None of the subjects had esters in organs such as the kidney and thyroid that are not susceptible to alcohol damage.
"Our results show that fatty acid ethyl esters are present in high concentrations and are synthesized in high rates in human organs frequently damaged by alcohol," says Lange.
"It seems that when one ingests alcohol, waves of fatty acid ethyl esters are made in certain organs. Then they disappear, whereas in fat tissue, they stay around. And the waves compare in magnitude and frequency roughly to the amount of ethanol ingestion. So people who drink more frequently would have potentially more tissue damage."
Meanwhile, the discovery has opened up new fields of research, raising the possibility of establishing alcohol use as a cause of death. "Individuals often have heart disease of no known cause or other diseases that may be related to alcohol ingestion," she says. "By being able to test samples of fat tissue for fatty acid ethyl esters, one could show that there has been long-term ethanol exposure. Before this, it was all word of mouth, and one could not document a history of drinking."
Such a test would also be useful to forensic scientists, says Lange. For example, some parents regularly sedate their children with alcohol. But if the children die with no alcohol in the bloodstream, such chemical abuse cannot be proven. Measuring fatty acid ethyl esters could reveal prior alcohol intake and even indicate its extent.
The researchers have not established a link between fatty acid ethyl esters and craving for alcohol. But, unlike acetaldehyde, the esters are formed in the brain. "The main problem in alcohol research is why people drink to excess, which comes down to how alcohol can affect brain function and therefore behavior," says Lange. "This pathway is the only one that can metabolize alcohol that has been described in the brain. So I would say that some basis has been laid for examining it."
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|Publication:||Nutrition Health Review|
|Date:||Jun 22, 1989|
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