ALCOHOL METABOLISM

Introduction:
Alcohol is the favorite mood-altering drug 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.

Prepared by: JE PEPITO-May '09

Introduction:

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.

Prepared by: JE PEPITO-May '09

Alcohol Metabolism Summary

Prepared by: JE PEPITO-May '09

Metabolic Fates of NADH:

The metabolic pathways for the disposal of excess NADH and the consequent
blocking of other normal metabolic pathways is shown in the graphic.
1. Pyruvic Acid to Lactic Acid:
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.
2. Synthesis of Lipids:
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.

Prepared by: JE PEPITO-May '09

Metabolic Fates of NADH:
3. Electron Transport Chain:
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.

Prepared by: JE PEPITO-May '09

Alcoholism Effects:
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.

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.

Prepared by: JE PEPITO-May '09