Ethanol metabolism
Have you guys met Dieter? He's the face of Chalk Talk! Now Dieter is celebrating something
very special today. He's celebrating Carnival, which is known in some countries as Mardi
Gras. During Carnival, people come together to celebrate before the start of Lent, the
forty day period before Easter. They often wear costumes and indulge in large quantities
of alcohol. Now, Dieter is drinking a beer with all of his friends. The ingested alcohol
from the beer is almost completely absorbed by Dieter’s body. It quickly enters the
bloodstream, spreads throughout his body, and eventually reaches the brain, where it
initiates its classical intoxicating effect. As the alcohol disseminates, it also starts
to metabolize. The primary site of ethanol metabolism is the liver. However, other organs
are also able to metabolize alcohol, but to a lesser degree. These include the kidneys,
lungs, and digestive organs.
Let’s take a closer look at the process of ethanol metabolism. In the first step,
ethanol is oxidized to acetaldehyde. By doing so, Dieter’s body makes things worse, as
acetaldehyde is even more toxic to cells than ethanol. In the cell, this reaction can occur
in three different ways. Most of the ethanol is oxidized by alcohol dehydrogenase. This
enzyme requires nicotinamide adenine dinucleotide, in short NAD+, as a cofactor.
A very small amount of ethanol can also be converted to acetaldehyde in other ways: by
catalase or by cytochrome-P450 dependent monooxygenase. The metabolic pathway via monooxygenase becomes
increasingly important with regular alcohol consumption since monooxygenase expression
is induced by ethanol. A large amount of reactive oxygen species is produced during the conversion
process involving monooxygenase, contributing to liver damage.
In the second step, acetaldehyde is converted into nontoxic acetate. This conversion is
catalyzed by acetaldehyde dehydrogenase and also requires NAD+ as a cofactor. Therefore,
the rate of ethanol metabolism is limited primarily by the recycling of NAD+.
During alcohol metabolism, the cell is in a special metabolic state with increased fatty
acid synthesis. This is because both NADH and acetate inhibit fatty acid degradation.
In addition, acetate is converted to acetyl-coenzyme A and can, therefore, be used as a building
block in energy metabolism, for example, in fatty acid synthesis. If Dieter would celebrate
carnival on a regular basis, he would eventually develop a beer belly.
The next day, Dieter has a very bad hangover from all that alcohol. This is due to the
build-up of acetaldehyde in the body and the dehydration associated with alcohol consumption.
As ethanol reduces anti-diuretic hormone release, this causes an increase in the amount of water
excreted by the kidneys.
If Dieter would develop an alcohol addiction as a result of regular consumption, Dieter’s
physician could also take advantage of the negative effects of acetaldehyde. The drug
disulfiram inhibits aldehyde dehydrogenase and slows the breakdown of acetaldehyde. As
a result, continued alcohol consumption causes increased discomfort. If large volumes of
alcohol are consumed despite disulfiram use, the result is a disulfiram-ethanol reaction
with moderate to severe adverse effects due to increased levels of acetaldehyde in the
blood.
Fortunately, Dieter only drinks alcohol occasionally. He hopes that you have fun celebrating Carnival.