**5. Byproducts of oxidative metabolism**

#### **5.1 Acetaldehyde**

Acetaldehyde has the power to cause tremendous damage regardless of its short life. This is particularly evident in the liver, where major alcohol metabolism occurs [17]. Minor alcohol metabolism also takes place in the pancreas [24] and the brain, causing damage to cells and tissues [13]. Additionally, small amount of alcohol is metabolized to acetaldehyde in the gastrointestinal tract, exposing it to damaging effects [22]. The International Agency for Research on Cancer [25] asserts that acetaldehyde should be classified as a carcinogen, it promotes cancer in several ways, for example, by interfering with replication of DNA and by inhibiting a process by which the body repairs damaged DNA [22]. Studies have shown that people who are exposed to large amounts of acetaldehyde are at greater risk for developing cancer of the mouth and throat [22].

Acetaldehyde possesses the ability to bind to various proteins like enzymes, microsomal proteins and microtubules. It combines with neurotransmitter dopamine and form salsolinol that cause alcohol dependence and also form DNA adducts, for example, 1,N2 -propanodeoxyguanosine which is carcinogenic [17]. However it is also reported that acetaldehyde concentrations in the brain are not high enough to produce these effects [26]. This is because the brain has a unique blood–brain barrier, which protects it from toxic products circulating in the bloodstream. However, it is possible that due to alcohol metabolism, acetaldehyde is produced in the brain by catalase [27, 28] and CYP2E1 [29].

Acetaldehyde may also be responsible for some of the behavioral and physiological effects previously attributed to alcohol [30]. For example, when acetaldehyde is administered to lab animals, it leads to in-coordination, memory impairment and sleepiness effects often associated with alcohol [26]. Deficiency of aldehyde dehydrogenase (ALDH2) leads to accumulation of acetaldehyde which results in facial flushing or blotches associated with erythema on the face, neck, shoulders, and in some cases, the entire body [31].

#### **5.2 Acetate**

Oxidation of acetaldehyde produce acetate which is later oxidized to carbon dioxide (CO2) in the heart, brain and skeletal muscles. Acetate is also metabolized

**127**

*Genetic Polymorphism and Alcohol Metabolism DOI: http://dx.doi.org/10.5772/intechopen.88907*

**6. Non-oxidative metabolism**

**7. The genetics of alcohol metabolism**

African-American people [40].

**8. Genetic polymorphism**

**8.1 Alcohol dehydrogenase (ADH)**

to acetyl CoA, which is involved in lipid and cholesterol biosynthesis in the mitochondria of peripheral and brain tissues. Acetate causes depression in the central

Ethanol is non-oxidatively metabolized by two pathways; first reaction is catalyzed by the enzyme fatty acid ethyl ester (FAEE) synthase leads to the formation of molecules known as FAEEs. In the second pathway, reaction with the enzyme phospholipase D (PLD) results in the formation of a phospholipid known as phosphatidyl

Alcohol metabolism involves both oxidative and non-oxidative inter related pathways. When ethanol oxidation is inhibited through enzyme inhibition, non-oxidative metabolism is increased along with increase in FAEEs in the liver and pancreas [33].

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the main enzymes of alcohol metabolism. Both the enzymes have several forms encoded by different genes. Enzymes with different characteristics having different ethnic distributions are because of variants of these genes. Since these enzyme variants work efficiently than others suggesting some people can metabolize alcohol more quickly, for example, a fast ADH enzyme or a slow ALDH enzyme may increase acetaldehyde level resulting in deleterious health effects including alcohol dependence [34]. A null allele is a mutant copy of a gene at a locus that completely lack normal function. This can result in to complete absence of the gene product (protein, RNA), or the expression of a non-functional gene product. At the phenotypic level,

Because of genetic difference in these enzymes, alcohol related problems are either higher or lower in some ethnic groups, for example, *ADH1B\*2*, a variant of ADH is common in people of China, Japan and Korea but rare in Europe and Africa [36]. Another version of the ADH enzyme *ADH1B\*3*, occurs in 15–25% of African Americans [37]. These enzymes protect against alcoholism [38] by elevating the level of acetaldehyde that make drinking unpleasant [39]. Two variations of the ALDH enzyme, *ALDH1A1\*2* and *ALDH1A1\*3*, may be associated with alcoholism in

Along with genetic factors, environmental factors are also important for alcoholism and alcohol-related health problems, for example, alcohol consumption increased from 2.5 to 13% in Japanese alcoholics who carried the protective ADH1B\*2 gene [41]. There is no difference in the rate of alcohol metabolism and enzyme pattern between Native Americans and Whites, more Native American people die of alcoholism than any other ethnic group in the United States [42]. This suggests that a rate of alcoholism and alcohol-related problems depends on environmental and genetic factors.

The major pathway of oxidative metabolism of ethanol in the liver involves ADH present in the cytosol. During oxidation an electron carrier nicotinamide adenine

a null allele is indistinguishable from a deletion of the entire locus [35].

ethanol [32]. This pathway is a critical component in cellular communication.

nervous system and also affects various metabolic processes [17].

*The Recent Topics in Genetic Polymorphisms*

**5. Byproducts of oxidative metabolism**

*Oxidative pathway of alcohol metabolism [17].*

Acetaldehyde has the power to cause tremendous damage regardless of its short life. This is particularly evident in the liver, where major alcohol metabolism occurs [17]. Minor alcohol metabolism also takes place in the pancreas [24] and the brain, causing damage to cells and tissues [13]. Additionally, small amount of alcohol is metabolized to acetaldehyde in the gastrointestinal tract, exposing it to damaging effects [22]. The International Agency for Research on Cancer [25] asserts that acetaldehyde should be classified as a carcinogen, it promotes cancer in several ways, for example, by interfering with replication of DNA and by inhibiting a process by which the body repairs damaged DNA [22]. Studies have shown that people who are exposed to large amounts of acetaldehyde are at greater risk for developing cancer of the mouth and throat [22]. Acetaldehyde possesses the ability to bind to various proteins like enzymes, microsomal proteins and microtubules. It combines with neurotransmitter dopamine and form salsolinol that cause alcohol dependence and also form DNA

However it is also reported that acetaldehyde concentrations in the brain are not high enough to produce these effects [26]. This is because the brain has a unique blood–brain barrier, which protects it from toxic products circulating in the bloodstream. However, it is possible that due to alcohol metabolism, acetaldehyde is

Acetaldehyde may also be responsible for some of the behavioral and physiological effects previously attributed to alcohol [30]. For example, when acetaldehyde is administered to lab animals, it leads to in-coordination, memory impairment and sleepiness effects often associated with alcohol [26]. Deficiency of aldehyde dehydrogenase (ALDH2) leads to accumulation of acetaldehyde which results in facial flushing or blotches associated with erythema on the face, neck, shoulders, and in

Oxidation of acetaldehyde produce acetate which is later oxidized to carbon dioxide (CO2) in the heart, brain and skeletal muscles. Acetate is also metabolized

produced in the brain by catalase [27, 28] and CYP2E1 [29].


**5.1 Acetaldehyde**

**Figure 1.**

adducts, for example, 1,N2

some cases, the entire body [31].

**126**

**5.2 Acetate**

to acetyl CoA, which is involved in lipid and cholesterol biosynthesis in the mitochondria of peripheral and brain tissues. Acetate causes depression in the central nervous system and also affects various metabolic processes [17].
