**2. Metabolism of alcohol**

When an alcoholic beverage is consumed, it passes through the stomach into the small intestine where the ethanol is rapidly absorbed and distributed throughout the body and more ethanol is found in the blood and the brain than in muscle or fat tissue. Around 2–8% of consumed alcohol is lost through urine, sweat, or the breath and the other 92–98% is metabolized in the liver. Alcohol is metabolized by several pathways. These pathways involves four enzymes—alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), catalase and microsomal ethanol oxidizing system (MEOS). These enzymes help break apart the alcohol molecule, making it possible to eliminate it from the body. In the first step, the primary pathway for alcohol metabolism involves alcohol dehydrogenase (ADH), a cytosolic enzyme that catalyzes the conversion of alcohol to acetaldehyde, a highly toxic substance and known carcinogen [2] (**Figure 1**). ADH is found mainly in the liver but can also be found in other organs of the body such as brain and stomach. During the process of conversion of ethanol to acetaldehyde, ethanol binds to alcohol dehydrogenase enzyme and loses some of its electrons in the form of hydrogen atoms to a coenzyme nicotinamide adenine dinucleotide (NAD) to form NADH. Ethanol oxidation generates an excess of reducing equivalents in the liver, mainly as NADH. NADH participates in numerous metabolic reactions in the body and for proper functioning of the body; the ratio of NAD to NADH must be tightly controlled. The conversion of ethanol to acetaldehyde by alcohol dehydrogenase enzyme reduces the cellular NAD to NADH ratio and this has profound effects on other liver metabolic pathways that require NAD or are inhibited by NADH. Decreased NAD/NADH ratio inhibits important reactions in the body such as glycolysis, tricarboxylic acid cycle (TCA cycle), fatty acid oxidation, pyruvate

**37**

**Figure 2.**

*Ethanol*

*DOI: http://dx.doi.org/10.5772/intechopen.79861*

more severe stage of liver disease.

consumption than others [7].

*Acetaldehyde dehydrogenases in ethanol and pyruvate metabolism.*

dehydrogenase and gluconeogenesis. Altered NAD/NADH ratio/elevated cellular NADH levels may lead to several metabolic disorders. Elevated levels of NADH could lead to the formation of abnormally high levels of lactic acid, which in turn reduces the capacity of the kidney to excrete uric acid. Excessive uric acid in the body can lead to gout, a disorder characterized by extremely painful swelling of joints [3]. Increased NADH promotes the generation of the building blocks of fat molecules (fatty acids) and reduces the breakdown of fats in the liver, thereby contributing to fat accumulation in that organ [4]. The resulting fatty liver is the earliest stage and the most common form of alcohol-induced liver disease. The elevation in NADH levels resulting from the ADH-mediated breakdown of alcohol also may play a role in the formation of scar tissue that characterizes fibrosis, a

Another pathway is the microsomal ethanol oxidizing system (MEOS). The primary component of the MEOS is the cytochrome P450, which exists in several variants. The variant most important for alcohol metabolism is cytochrome P450 2E1 (CYP2E1) [5]. This pathway uses NADPH as a coenzyme in the metabolism of ethanol and results in the formation of NADP and water (**Figure 1**). The cytochrome CYP2E1/MEOS pathway is only active after a person has consumed large amounts of alcohol [6]. Alcohol breakdown by microsomal ethanol oxidizing system generates several highly reactive oxygen-containing molecules called reactive oxygen species (ROS). These reactive oxygen species can damage liver cells by inactivating essential enzymes and altering the breakdown of fat molecules and when there is an imbalance between ROS and antioxidant systems, a condition known as oxidative stress sets in which can cause liver cell damage. Alcohol and its metabolism have been shown to reduce the levels of both glutathione (GSH) and vitamin E (α-tocopherol) which protects the body against ROS [6]. The catalase pathway metabolizes only a small fraction of alcohol in the body [2]. In the second step, acetaldehyde is further metabolized down by aldehyde dehydrogenase (ALDH) to another less active by product called acetate (**Figures 2** and **3**) which in turn is broken down into carbon dioxide and water. Ethanol is mainly eliminated from the body via metabolism into carbon dioxide and water. Acetate/acetic acid combine with Coenzyme A to form acetyl-CoA. The acetyl-CoA enters the tricarboxylic acid (TCA) cycle/Krebs cycle. In the Krebs cycle, acetate in the form of acetyl CoA is broken down into carbon dioxide and in this process ATP is formed (**Figure 3**) [2]. Some individuals have less effective forms of ethanol metabolizing enzymes and can experience more marked symptoms from ethanol

**Figure 1.** *Metabolism of ethanol to acetic acid/acetate.*

### *Ethanol DOI: http://dx.doi.org/10.5772/intechopen.79861*

*Psychology of Health - Biopsychosocial Approach*

gases emanation from use of fossil fuels.

**2. Metabolism of alcohol**

fuel sources is that it does not cause pollution to the environment thereby reducing global warming which is caused by relentless emission of dangerous greenhouse

When an alcoholic beverage is consumed, it passes through the stomach into the small intestine where the ethanol is rapidly absorbed and distributed throughout the body and more ethanol is found in the blood and the brain than in muscle or fat tissue. Around 2–8% of consumed alcohol is lost through urine, sweat, or the breath and the other 92–98% is metabolized in the liver. Alcohol is metabolized by several pathways. These pathways involves four enzymes—alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), catalase and microsomal ethanol oxidizing system (MEOS). These enzymes help break apart the alcohol molecule, making it possible to eliminate it from the body. In the first step, the primary pathway for alcohol metabolism involves alcohol dehydrogenase (ADH), a cytosolic enzyme that catalyzes the conversion of alcohol to acetaldehyde, a highly toxic substance and known carcinogen [2] (**Figure 1**). ADH is found mainly in the liver but can also be found in other organs of the body such as brain and stomach. During the process of conversion of ethanol to acetaldehyde, ethanol binds to alcohol dehydrogenase enzyme and loses some of its electrons in the form of hydrogen atoms to a coenzyme nicotinamide adenine dinucleotide (NAD) to form NADH. Ethanol oxidation generates an excess of reducing equivalents in the liver, mainly as NADH. NADH participates in numerous metabolic reactions in the body and for proper functioning of the body; the ratio of NAD to NADH must be tightly controlled. The conversion of ethanol to acetaldehyde by alcohol dehydrogenase enzyme reduces the cellular NAD to NADH ratio and this has profound effects on other liver metabolic pathways that require NAD or are inhibited by NADH. Decreased NAD/NADH ratio inhibits important reactions in the body such as glycolysis, tricarboxylic acid cycle (TCA cycle), fatty acid oxidation, pyruvate

**36**

**Figure 1.**

*Metabolism of ethanol to acetic acid/acetate.*

dehydrogenase and gluconeogenesis. Altered NAD/NADH ratio/elevated cellular NADH levels may lead to several metabolic disorders. Elevated levels of NADH could lead to the formation of abnormally high levels of lactic acid, which in turn reduces the capacity of the kidney to excrete uric acid. Excessive uric acid in the body can lead to gout, a disorder characterized by extremely painful swelling of joints [3]. Increased NADH promotes the generation of the building blocks of fat molecules (fatty acids) and reduces the breakdown of fats in the liver, thereby contributing to fat accumulation in that organ [4]. The resulting fatty liver is the earliest stage and the most common form of alcohol-induced liver disease. The elevation in NADH levels resulting from the ADH-mediated breakdown of alcohol also may play a role in the formation of scar tissue that characterizes fibrosis, a more severe stage of liver disease.

Another pathway is the microsomal ethanol oxidizing system (MEOS). The primary component of the MEOS is the cytochrome P450, which exists in several variants. The variant most important for alcohol metabolism is cytochrome P450 2E1 (CYP2E1) [5]. This pathway uses NADPH as a coenzyme in the metabolism of ethanol and results in the formation of NADP and water (**Figure 1**). The cytochrome CYP2E1/MEOS pathway is only active after a person has consumed large amounts of alcohol [6]. Alcohol breakdown by microsomal ethanol oxidizing system generates several highly reactive oxygen-containing molecules called reactive oxygen species (ROS). These reactive oxygen species can damage liver cells by inactivating essential enzymes and altering the breakdown of fat molecules and when there is an imbalance between ROS and antioxidant systems, a condition known as oxidative stress sets in which can cause liver cell damage. Alcohol and its metabolism have been shown to reduce the levels of both glutathione (GSH) and vitamin E (α-tocopherol) which protects the body against ROS [6]. The catalase pathway metabolizes only a small fraction of alcohol in the body [2].

In the second step, acetaldehyde is further metabolized down by aldehyde dehydrogenase (ALDH) to another less active by product called acetate (**Figures 2** and **3**) which in turn is broken down into carbon dioxide and water. Ethanol is mainly eliminated from the body via metabolism into carbon dioxide and water. Acetate/acetic acid combine with Coenzyme A to form acetyl-CoA. The acetyl-CoA enters the tricarboxylic acid (TCA) cycle/Krebs cycle. In the Krebs cycle, acetate in the form of acetyl CoA is broken down into carbon dioxide and in this process ATP is formed (**Figure 3**) [2]. Some individuals have less effective forms of ethanol metabolizing enzymes and can experience more marked symptoms from ethanol consumption than others [7].

**Figure 2.** *Acetaldehyde dehydrogenases in ethanol and pyruvate metabolism.*

#### **Figure 3.**

*Metabolism of ethanol to acetyl CoA. Numbered reactions are catalyzed by the following enzymes: 1: mitochondrial pyruvate carrier; 2: pyruvate dehydrogenase complex; 3: pyruvate decarboxylase; 4: acetaldehyde dehydrogenase; 5: acetyl-CoA synthetase; 6: carnitine shuttle; 7: alcohol dehydrogenase; 8: pyruvate carboxylase.*
