Alcohol Metabolism

http://www.elmhurst.edu/~chm/vchembook/642alcoholmet.html

Energy Summary
Serum Enzymes Alcohol Metab. Effects

Glycolysis & Citric Cycle Lipid Metabolism Protein Metabolism

Elmhurst College Chemistry Department Virtual ChemBook

Alcohol Metabolism Effects

Alcohol is the favorite mood-altering drug in the United States and its effects, both pleasant and unpleasant, are well-known. What may not be well known is the fact that alcohol is a toxic drug that produces pathological changes (cirrhosis) in liver tissue and can cause death. Alcohol is readily absorbed from the gastrointestinal tract; however, alcohol cannot be stored and therefore, the body must oxidize it to get rid of it. Alcohol can only be oxidized in the liver, where enzymes are found to initiate the process. In addition, alcohol directly contributes to malnutrition since a pint of 86 proof alcohol (not an unusual daily intake for an alcoholic) represents about half of the daily energy requirement. However, ethanol does not have any minerals, vitamins, carbohydrates, fats or protein associated with it. Alcohol causes inflammation of the stomach, pancreas, and intestines which impairs the digestion of food and absorption into blood. Moreover, the acetaldehyde (the oxidation product) can interfere with the activation of vitamins. Click for larger image The first step in the metabolism of alcohol is the oxidation of ethanol to acetaldehyde catalyzed by alcohol/dehydrogenase containing the coenzyme NAD+. The acetaldehyde is further oxidized to acetic acid and finally CO2 and water through the citric acid cycle. A number of metabolic effects from alcohol are directly linked to the production of an excess of both NADH and acetaldehyde. CH3CH2OH + NAD+ ---> CH3CH=O + NADH + H+ The red box shows the above reaction.
(Adapted from C.S. Lieber, Sci. Am. 234(3), 25(1976)

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Alcohol Metabolism

http://www.elmhurst.edu/~chm/vchembook/642alcoholmet.html

The metabolic pathways for the disposal of excess NADH and the consequent blocking of other normal metabolic pathways is shown in the graphic on the left.

The conversion of pyruvic acid to lactic acid requires NADH: Pyruvic Acid + NADH + H+ ---> Lactic Acid + NAD+ This pyruvic acid normally made by transamination of amino acids, is intended for conversion into glucose by gluconeogenesis. This pathway is inhibited by low concentrations of pyruvic acid, since it has been converted to lactic acid. The final result may be acidosis from lactic acid build-up and hypoglycemia from lack of glucose synthesis.

Click for larger image

Excess NADH may be used as a reducing agent in two pathways--one to synthesize glycerol (from a glycolysis intermediate) and the other to synthesis fatty acids. As a result, heavy drinkers may initially be overweight.

The NADH may be used directly in the electron transport chain to synthesize ATP as a source of energy. This reaction has the direct effect of inhibiting the normal oxidation of fats in the fatty acid spiral and citric acid cycle. Fats may accumulate or acetyl CoA may accumulate with the resulting production of ketone bodies. Accumulation of fat in the liver can be alleviated by secreting lipids into the blood stream. The higher lipid levels in the blood may be responsible for heart attacks.

A central role in the toxicity of alcohol may be played by acetaldehyde itself. Although the liver converts acetaldehyde into acetic acid, it reaches a saturation point where some of it escapes into the blood stream. The accumulated acetaldehyde exerts its toxic effects by inhibiting the mitochondria reactions and functions. The alcoholic is a victim of a vicious circle; a high acetaldehyde level impairs mitochondria function, metabolism of acetaldehyde to acetic acid decreases, more acetaldehyde accumulates, and causes further liver damage--hepatitis and cirrhosis.

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Alcohol Metabolism

http://www.elmhurst.edu/~chm/vchembook/642alcoholmet.html

Recent investigations have suggested that acetaldehyde may be responsible for the development of alcohol addiction. Acetaldehyde in the brain may inhibit enzymes designed to convert certain nerve transmitters from aldehydes to acids. The nerve transmitters that accumulate may then react with the acetaldehyde to form compounds which are startlingly similar to certain morphine-type compounds.

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