Overview: How Is Alcohol Metabolized by the Body? PMC

Firstly, normal metabolism increases, as shown by high blood concentrations of acetate. Secondly, the microsomal ethanol oxidising system is brought into play; this is dependent on cytochrome P450, which is normally responsible for drug metabolism, and other cofactors. This process is called enzyme induction, and the effect is also produced by other drugs that are metabolised by the liver and by smoking.​smoking. The second nonoxidative pathway requires the enzyme phospholipase D (PLD) (Laposata 1999), which breaks down phospholipids (primarily phosphatidylcholine) to generate phosphatidic acid (PA). PLD has a high Km for ethanol, and the enzymatic reaction does occur predominantly at high circulating alcohol concentrations.

Overview: How Is Alcohol Metabolized by the Body?

  • Under normal circumstances, acetate is oxidised in the liver and peripheral tissues to carbon dioxide and water.
  • This small amount of alcohol (5-10%) is eliminated unchanged in the breath as vapor or in the urine.
  • Fetal alcohol spectrum disorders are a group of disorders, the most severe of which is fetal alcohol syndrome.
  • Antibodies directed against other acetaldehyde–protein adducts also have been found in the blood of alcoholics (Lin et al. 1990; Worrall et al. 1990).
  • Alcohol inhibits NMDA receptors, which are responsible for synaptic plasticity (how neurons change the strength of their connections) and are tied to memory.

The perivenous hepatocytes also are the first ones to show evidence of damage from chronic alcohol consumption (Ishak et al. 1991), indicating the potential harmful consequences of hypoxia induced by ethanol metabolism. The relative contributions of these factors to the increase in ROS levels is unknown (Bailey 2003). Regardless of how they were generated, however, increases in ROS levels have numerous detrimental effects.

  • Can the fluctuations in cellular redox state resulting from ethanol metabolism directly influence ethanol-induced liver injury?
  • There are many reasons why drinking alcohol would result in undesirable effects.
  • Acetaldehyde–lysine adducts were detected in the plasma membrane of hepatocytes from alcohol-fed rats (Barry et al. 1987).

Behavioural effects

  • As mentioned earlier, the main pathway of alcohol metabolism, which involves ADH and ALDH, results in the generation of NADH.
  • These and other findings indicate a link between MDA, HNE, and MAA adducts and subsequent development of liver disease (Tuma and Casey 2003).
  • Alcohol also triggers neurotransmitters like dopamine and serotonin, creating a feeling of relaxation and well-being.
  • To prevent the damage these highly reactive compounds can cause, numerous defense systems have evolved in the body involving compounds called antioxidants, which can interact with ROS and convert them into harmless molecules.

These consequences and the way they contribute to tissue damage and disease will be discussed in the following sections. The body has a natural way to “get rid” of the acetaldehyde…remember, this is toxic to the body. There is a second liver enzyme, present in the mitochondria, called acetaldehyde dehydrogenase (ALDH). The acetic acid is eventually converted in the cell into carbon dioxide and water.

about 10% of all alcohol eliminated by the body comes from the lungs, kidneys and perspiration.

Formation of ROS and Decrease in Antioxidants

When this balance is disturbed and an excess of ROS is present, a state known as oxidative stress results. As mentioned earlier, ethanol metabolism by CYP2E1 and NADH oxidation by the electron transport chain generate ROS that results in lipid peroxidation. This process results in the formation of compounds known as malondialdehyde (MDA) and 4hydroxy-2-nonenal (HNE), both of which can form adducts with proteins (Worrall and Thiele 2001).

about 10% of all alcohol eliminated by the body comes from the lungs, kidneys and perspiration.

One of these molecules is prostaglandin E2, which stimulates the metabolic activity of hepatocytes—that is, it induces them to break down and synthesize many essential molecules through a variety of chemical reactions that also require oxygen. As a result, alcohol-induced Kupffer cell activation also contributes to the onset of hypoxia. The ADH gene family encodes enzymes that metabolize various substances, including ethanol. When ethanol is present, the metabolism of the other substances that ADH acts on may be inhibited, which may contribute to ethanol-induced tissue damage. Variations in the rate of alcohol absorption, distribution, and elimination contribute significantly to clinical conditions observed after chronic alcohol con sumption.

  • Figure 1.11 Ethanol is oxidized by ADH to acetaldehyde in the cytoplasm, and then the acetaldehyde is oxidized by ALDH in the mitochondria to acetic acid.
  • Today, much is known about ethanol metabolism, particularly its oxidation by ADH and ALDH in the liver.
  • As mentioned earlier, phospholipase D normally is a critical component in cellular signal transduction processes, and the presence of ethanol interferes with these pathways.
  • ROS, including superoxide (O2•−), hydrogen peroxide (H2O2), hypochlorite ion (OCl−), and hydroxyl (•OH) radicals, are naturally generated by many reactions in multiple regions of the cell.

Other factors

In addition, a deeper understanding of these processes will allow researchers to design intervention strategies that may ameliorate the harmful effects of alcohol and its metabolites. The primary enzymes involved are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2E1), and catalase. Variations in the genes for these enzymes have been found to influence alcohol consumption, alcohol-related tissue damage, and alcohol dependence. The major pathway of oxidative how does alcohol affect the kidneys metabolism of ethanol in the liver involves ADH (present in the fluid of the cell [i.e., cytosol]), an enzyme with many different variants (i.e., isozymes). Metabolism of ethanol with ADH produces acetaldehyde, a highly reactive and toxic byproduct that may contribute to tissue damage and, possibly, the addictive process. As shown in Table 1, ADH constitutes a complex enzyme family, and, in humans, five classes have been categorized based on their kinetic and structural properties.

Genetic Variation in ADH and ALDH

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