Alcohol Dehydrogenase: Mechanism & Pathway

Instructor: Laura Foist

Laura has a Masters of Science in Food Science and Human Nutrition and has taught college Science.

Alcohol dehydrogenase is the first step the body uses to breakdown alcohol. In this lesson we will learn how this reaction occurs, where it occurs in the body, and what the products of the reaction are used for.

Making Alcohol Safe

Ethanol is the typical alcohol found in alcoholic drinks and is highly toxic to the body. So how can you enjoy a drink at the bar without dying? The body has a method for taking care of any ethanol that enters the body safely.

The first enzyme in this process is alcohol dehydrogenase. Alcohol dehydrogenase is a zinc based enzyme that converts ethanol into acetaldehyde. There are several different forms, but they all perform the same function with the same mechanism pathway. The different forms can be found in the stomach and liver.

Okay, so then why is drinking alcohol a concern at all? Well, the enzymes used to change alcohol into a safe substance can only handle so much at a time. Too much at once and it won't be able to process it all, and you can end up with alcohol poisoning. Let's look into the mechanism of converting alcohol in more detail.

Enzyme Mechanism

The general mechanism is simply ethanol + NAD forms acetaldehyde + NADH. In other words, ethanol is oxidized into acetaldehyde and the hydrogen atoms are added to NAD. Recall that an alcohol is any carbon chain with a carbon attached to an OH group while an aldehyde is any carbon chain with the terminal carbon forming a double bond with oxygen.

The active site of alcohol dehydrogenase includes a serine, a histidine, an isoleucine and a zinc stabilized by two cysteines, and a histidine.

The active site includes a zinc, serine, hisitidine, isoleucine, and cysteine
Active site

The oxygen in the alcohol binds to the zinc. The NAD is bound to the isoleucine. There are two main steps in the alcohol hydrogenase mechanism:

  1. Hydrogen is removed from the OH on the alcohol.
  2. A carbon-oxygen double bond forms, hydrogen is removed from the carbon and added to NAD to form NADH.

The alcohol and NAD are connected to the enzyme with the isoleucine and zinc
Connect to enzyme

In step 1 the histidine takes a hydrogen from NAD, the NAD then takes a hydrogen from serine, which in turn takes the hydrogen from the OH on the alcohol.

Histidine removes a hydrogen from NAD, which in turn removes a hydrogen from serine, which removes the hydrogen from the alcohol
Step 1

The products of step 1 includes a NAD molecule and the alcohol without a hydrogen on the oxygen
Products step 1

In step 2 the electrons from the oxygen can then form a double bond with carbon and the electrons in the carbon-hydrogen bond are added (with the hydrogen) to the 6 membered ring on NAD, forming NADH and the acetaldehyde.

In step 2 the hydrogen is removed from the carbon and put onto NAD, forming NADH, also the carbon oxygen double bond is formed.
Step 2

We end up with an aldehyde and NADH
Final products

Alcohol Dehydrogenase Pathway

The reaction takes place in several places in the body, but mostly in the stomach and liver. Acetaldehyde is actually even more toxic to the body than alcohol, but it can quickly be converted into acetic acid, which is used to make energy.

One of the reasons for feeling a hangover after drinking alcohol is due to this breakdown of alcohol in the body. Water is needed to detoxify the end products of alcohol dehydrogenase, so the body ends up dehydrated, thus accounting for hangover symptoms.

This pathway isn't only applicable to ethanol, but it is applicable to all alcohol molecules, the end products will just be slightly different. The alcohol is always converted into the aldehyde, but sometimes the aldehydes that are formed cannot be further used in the body and are highly toxic.

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