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Enzyme Lack Lowers Women's Alcohol Tolerance

An international team of researchers may have found one of the reasons why alcohol harms women more than men: women, it appears, are deficient in an enzyme that helps metabolize alcohol. The findings appear in the April issue of Alcoholism: Clinical and Experimental Research. "It has been known for a long time that, in general, both women and female animals are more susceptible to the negative or toxic effects of alcohol," team member Steven Schenker of the University of Texas at San Antonio says. "This is true for the liver, heart muscle and skeletal muscle, and it may be true for the pancreas and the brain. In other words, there is something about the female gender that makes them more susceptible to toxic amounts of alcohol."

In the past scientists attributed this susceptibility to women's smaller body size and their relatively higher percentage of fatty tissue. For this study, however, the researchers focused on what is known as first-pass metabolism. Before alcohol reaches the blood stream, it goes through the stomach, where so-called gastric alcohol dehydrogenase (ADH) isozymes break some of it down. "In an earlier study we found that women have less of this ADH activity than men do," notes lead author Charles Lieber of the Mount Sinai School of Medicine. "Accordingly, women have a lesser first-pass metabolism and, therefore, for a given dose of alcohol, their blood level is higher than it is for men."

Following up on that research, the team recently turned their attention to the makeup of ADH. They found that one of the enzyme's three components, glutathione-dependent fomaldehyde dehydrogenase (x-ADH), is deficient in women, thus explaining their lower ADH activity levels. To Schenker, the take-home message is clear: "Women simply need to be more cautious than males in terms of the amount of drinking they do."

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