Although these genetic factors influence drinking patterns, environmental factors also are important in the development of alcoholism and other alcohol-related health consequences. Additionally, despite the fact that more Native American people die of alcohol-related causes than do any other ethnic group in the United States, research shows that there is no difference in the rates of alcohol metabolism and enzyme patterns between Native Americans and Whites Alcohol metabolism and cancer— Alcohol consumption can contribute to the risk for developing different cancers, including cancers of the upper respiratory tract, liver, colon or rectum, and breast This occurs in several ways, including through the toxic effects of acetaldehyde Alcohol is metabolized in the body mainly by the liver.
The brain, pancreas, and stomach also metabolize alcohol. Many heavy drinkers do not develop cancer, and some people who drink only moderately do develop alcohol-related cancers.
Ironically, the very genes that protect some people from alcoholism may magnify their vulnerability to alcohol-related cancers. The International Agency for Research on Cancer 21 asserts that acetaldehyde should be classified as a carcinogen. Acetaldehyde promotes cancer in several ways—for example, by interfering with the copying i.
Studies have shown that people who are exposed to large amounts of acetaldehyde are at greater risk for developing certain cancers, such as cancers of the mouth and throat 5.
Although these individuals often are less likely to consume large amounts of alcohol, Seitz and colleagues 5 suggest that when they do drink their risk for developing certain cancers is higher than drinkers who are exposed to less acetaldehyde during alcohol metabolism. Acetaldehyde is not the only carcinogenic byproduct of alcohol metabolism.
ROS can damage proteins and DNA or interact with other substances to create carcinogenic compounds Poor nutrition may cause the mother to metabolize alcohol more slowly, exposing the fetus to high levels of alcohol for longer periods of time Increased exposure to alcohol also can prevent the fetus from receiving necessary nutrition through the placenta In rats, maternal malnutrition has been shown to contribute to slow fetal growth, one of the features of FASD, a spectrum of birth defects associated with drinking during pregnancy These findings suggest that managing nutrition in pregnant women who drink may help to reduce the severity of FASD More than 90 percent of people who drink heavily develop fatty liver, a type of liver disease.
Yet only 20 percent will go on to develop the more severe alcoholic liver disease and liver cirrhosis Alcoholic pancreatitis— Alcohol metabolism also occurs in the pancreas, exposing this organ to high levels of toxic byproducts such as acetaldehyde and FAEEs 3. Still, less than 10 percent of heavy alcohol users develop alcoholic pancreatitis—a disease that irreversibly destroys the pancreas— suggesting that alcohol consumption alone is not enough to cause the disease.
Researchers speculate that environmental factors such as smoking and the amount and pattern of drinking and dietary habits, as well as genetic differences in the way alcohol is metabolized, also contribute to the development of alcoholic pancreatitis, although none of these factors has been definitively linked to the disease Two methods that are helping researchers gain a better understanding of how alcohol is metabolized are the alcohol clamp method, in which alcohol is given intravenously, and the use of specially grown cells.
The alcohol clamp method. The speed at which people absorb, distribute, and metabolize alcohol varies as much as three or four times between individuals 1,2.
The alcohol clamp is a method of administering alcohol intravenously to subjects, allowing researchers to circumvent variations in alcohol absorption.
This technique enables researchers to administer precise doses of alcohol to achieve an exact breath alcohol concentration a measure of how much alcohol is in the body 3,4. The actual dose of alcohol is calculated for each individual based on his or her specific alcohol elimination rate, controlling for factors like gender and body mass. This allows researchers to compare the alcohol elimination or metabolism rates without complicating factors.
For example, using the alcohol clamp method researchers were able to determine that male volunteers eliminated alcohol at significantly faster rates than did female volunteers 5—8. The alcohol clamp method also helps researchers study the genetics of alcohol metabolism, including differences in how volunteers who carry different versions of the ADH and ALDH genes metabolize alcohol 9. Cultured cells.
Cells that are grown in the laboratory i. Additionally, because large quantities of cells can be cloned, researchers are able to repeat experiments many times in order to confirm findings. Variability of ethanol absorption and breath concentrations during a large-scale alcohol administration study.
Alcoholism: Clinical and Experimental Research —, Gender and ethnic differences in alcohol metabolism. Clamping breath alcohol concentration reduces experimental variance: Application to the study of acute tolerance to alcohol and alcohol elimination rate. The alcohol clamp: Applications, challenges and new directions. Gender differences in alcohol metabolism: Relationship to liver volume and effect of adjusting for body mass.
Figure 1. It diffuses into hepatic cells of the liver where it is metabolized. Metabolism of drugs by liver enzymes serves two purposes. In general, metabolites have less biological activity relative to the parent compound, although there are some exceptions to this rule, as we will see with ethanol.
Second, metabolism helps to convert the drug into a more polar water-soluble form so it can be carried in the bloodstream to the kidneys, where it is excreted in the urine water-based. During metabolism, the enzymes actually help speed up the reactions; however, the speed is different for different people. Review enzymes as catalysts. Although some alcohol is metabolized in the stomach, the primary site of metabolism is in the liver.
The cytoplasm of liver cells contain an enzyme called alcohol dehydrogenase ADH that catalyzes the oxidation of ethanol to acetaldehyde Figure 1. The oxidation occurs when ethanol binds to a site on the ADH enzyme and loses some electrons in the form of H atoms. Actually ethanol gives up 2 H atoms to another molecule that also binds to ADH.
In this case, the recipient molecule of the electrons is called a coenzyme. The primary metabolite of ethanol oxidation, is acetaldehyde. This compound is relatively toxic, and it is responsible for alcohol-related flushing, headaches, nausea, and increased heart rate.
This enzyme metabolizes acetaldehyde to acetic acid Figure 1. The acetic acid is eventually converted in the cell into carbon dioxide and water. Some people do not have the ability to metabolize acetaldehyde very well. When they drink alcohol, acetaldehyde accumulates in the blood and makes them feel sick. They have facial flushing, headaches, nausea, vomiting, and a rapid heart rate. The alternative form of ALDH is very inefficient at metabolizing acetaldehyde.
Research has shown that women may have less ADH enzyme activity in the stomach, allowing a larger percentage of alcohol to reach the blood before being metabolized. This could be one reason women who drink are more susceptible to alcohol liver disease, heart muscle damage, and brain damage than men.
Genetics can also be a factor in whether or not the person is susceptible to developing alcohol use disorders. For example, there is one variation of these enzymes that causes a build-up of acetaldehyde to the point it causes facial flushing, nausea, and a rapid heart rate. These effects can occur with even moderate alcohol consumption. This gene variant is common in people of Chinese, Japanese, and Korean descent, who may drink less because of the unpleasant side effects.
Their gene variant has a protective effect against developing alcoholism. According to the National Library of Medicine NLM , alcohol use disorder does not have a clear pattern of genetic inheritance, but the children of people with alcohol use disorder are still two to six times more likely than the general population to develop problems with alcohol use themselves.
This increased risk may, in part, be a result of some shared genetic factors, but experts also believe that shared environmental and social factors likely are at play as well. In the United States, more Native Americans die of alcohol-related causes than any other ethnic group, but researchers found there is no difference in the enzyme patterns or alcohol metabolism rates of Native Americans and Caucasians, indicating that there are other factors at play in the development of alcohol-related problems.
Heavy or chronic alcohol consumption has been linked to a long list of negative health consequences and long-term adverse effects. Some of these health problems have been directly linked to how alcohol is metabolized in the body and the production of acetaldehyde.
The toxic effects of acetaldehyde have been linked to the development of cancers of the mouth, throat, upper respiratory tract, liver, colon, and breasts.
Ironically, the genes that "protect" some individuals from developing alcoholism may actually increase their vulnerability to developing cancer. Although they are less likely to drink large amounts of alcohol, these people are at greater risk for developing cancer because their bodies produce more acetaldehyde when they do drink.
So, even some moderate drinkers are a greater risk of developing cancer. Because the liver is the organ that metabolizes most of the alcohol in the body and therefore is where most of the acetaldehyde is produced, it is particularly vulnerable to the effects of alcohol metabolism.
Because some alcohol metabolism also takes place in the pancreas, it is exposed to high levels of acetaldehyde and FAEEs. Other factors may include smoking, diet, drinking patterns and the differences in how alcohol is metabolized may play a role, but none have been definitively linked to pancreatitis.
Alcohol consumption does not necessarily lead to increased body weight, in spite of its relatively high caloric value. Although moderate alcohol consumption does not lead to weight gain in lean men or women, studies have found that alcohol added to the diets of overweight people does lead to weight gain. In men, alcohol metabolism contributes to testicular injury and impairs testosterone synthesis and sperm production. Prolonged testosterone deficiency may contribute to feminization in males, such as breast enlargement.
In women, alcohol metabolism may cause increased production of estradiol and decreased estradiol metabolism, resulting in increased levels.
Estradiol contributes to increased bone density and a reduced risk of coronary artery disease. Alcohol consumption affects the metabolism of many different medications, increasing the activity of some and diminishing the effectiveness of others.
Chronic heavy drinking has been found to activate the CYP2E1 enzyme, which can change acetaminophen into a toxic chemical that can cause liver damage even when taken in regular therapeutic doses.
National Institute on Alcohol Abuse and Alcoholism funded research continues to examine how variations in the way the body metabolizes alcohol may influence why some people drink more than others and why some develop serious alcohol-related health problems.
Researchers believe how the body breaks down and eliminates alcohol may hold the key to explaining the differences, and continued research may help in developing metabolism-based treatments for people who drink who are at risk for developing alcohol-related health problems.
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