Alcohol Liver Disease Essay

720 words - 3 pages

After absorption into the blood-stream, alcohol is distributed quickly throughout the body and metabolized by most tissues. However, the major site of alcohol metabolism is liver. The liver can metabolize only a certain amount of alcohol per hour, regardless of the amount that has been consumed. Ethanol metabolism occurs through oxidative (major) and non-oxidative (minor) routes. During the oxidative route ethanol is oxidized to acetaldehyde, a highly reactive and toxic byproduct, by several pathways that require the presence of specific enzymes: alcohol dehydrogenase (ADH) located in mitochondria, microsomal cytochrome P450 (CYP450) located on endoplasmic reticulum, and catalase in hepatic peroxisomes. After formation, acetaldehyde is subsequently metabolized by mitochondrial aldehyde dehydrogenases (ALDHs) to acetic acid, or acetate, which occurs endogenously in human body. Most of the acetate resulting from alcohol metabolism enters the circulation and is eventually metabolized to CO2 in cardiac, skeletal muscle, and brain cells. Non-oxidative alcohol metabolism predominantly occurs in organs where oxidative metabolism is rare or absent, such as pancreas and heart. This minor route of ethanol metabolism results in the esterification of ethanol with endogenous fatty acids or fatty acyl coenzyme A to fatty acid ethyl esters (FAEEs) under the influence of FAEE synthase, and in the formation of poorly metabolized phosphatidylethanol, a fat molecule containing phosphorus, with the help of enzyme phospholipase D (PLD). Small amounts of non-metabolized alcohol are eliminated by kidney with urine, by lungs with breath, and by skin with sweat.
The rate of alcohol metabolism depends, in part, on the functioning of metabolizing enzymes in the liver, which varies among individuals and is believed to have genetic determinants. For instance, polymorphism of ADH, responsible for the metabolism of ethanol to acetaldehyde, occurs at the ADH1B and ADH1C gene locations and is associated with varying levels of enzymatic activity. The ADH1B*1 form is found predominantly in Caucasian and Black populations, whereas ADH1B*2 frequency is higher in Chinese and Japanese populations. Individuals carrying the ADH1B*2 and ADH1B*3 alleles tend to metabolize and eliminate alcohol at a faster rate than those with the ADH1B*1 form. Genetic polymorphism of the ALDH2 gene, which together with ALDH1 catalyzes the...

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