Ethanol Metabolism: What does the body do with alcohol?

If you’re here reading my blog, chances are you have, at some point in your life, imbibed a few alcoholic beverages.  And if you’re anything like me, you have found yourself wondering “So what does the body do with that alcohol, anyways?”

There are a vast number of “alcohols,” a broad term for molecules with an -OH “hydroxyl” functional groupcomposed of one oxygen and one hydrogen atomattached to a central carbon atom or chain.  The primary alcohol in beer, wine, etc. is ethanol, CH3CH2OH.  Ethanol passes readily through bodily membranes, including the blood-brain barrier.

ethanol molecule

Effects of Alcohol

Once ethanol reaches the brain, it effects some areas more than others, specifically the prefrontal cortex, hippocampus, and cerebellum.  These regions control higher thinking and judgement, memory, and motor control, respectively.  They have relatively higher levels of the rare 𝛿-subunit-containing variant of the GABAA neuroreceptor, which interacts more strongly with ethanol than the standard GABAA receptor, making these regions more susceptible to the depressive effects of ethanol.

Rising ethanol levels in the body cause elation, excitement, extroversion, and an increase in norepinephrine, the neurotransmitter responsible for arousal and impulsivity.  Conversely, as levels fall, fatigue, relaxation, confusion, and depression set in.  Ethanol is actually a toxin, with the desired pleasant effects happening at very low blood alcohol levels.  Being a toxin, the body must somehow get rid of it.

Getting Rid of Ethanol

The body gets rid of ethanol in many ways.  Minor pathways include the exhalation from the lungs and excretion through the skin, but the vast majority is metabolized with the help of enzymes, primarily in the liver.

(1) Ethanol to Acetaldehyde

80-90% of ethanol metabolism starts with the alcohol dehydrogenase enzyme, or ADH.  Along with the help of a molecule called NAD (nicotinamide adenine dinucleotide, if you were curious), it turns ethanol into acetaldehyde (yes, that acetaldehyde, responsible for that green-apple off-flavor).  NAD is a helper molecule which scuttles electrons back and forth in many bio-chemical reactions, and exists in the NAD+ form, capable of receiving electrons (an oxidizing agent), and NADH form, capable of giving electrons (a reducing agent).

The net result is two hydrogen atoms are stripped from the ethanol molecule.  You might have guessed this result by looking carefully at the name of the enzyme; alcohol: active on alcohol; de-hydrogen: removing hydrogen; -ase: the suffix given to enzymes.  One hydrogen is removed from the characteristic -OH hydroxyl group (thus it is no longer an alcohol, as there is no -OH group).  The other is released from the carbon atom so it can form two bonds with the attached oxygen; oxygen likes to have two bonds, and carbon likes to have four.

Looking at the image below, you can see the four bonds on the right-most carbon in acetaldehyde are: one with the carbon to the left, one with the hydrogen (hydrogen can form only one bond), and two with the oxygen.  In ethanol, the oxygen had its own bond with a hydrogen, so could only form a single bond with the right carbon atom, so the carbon needed another hydrogen to form four bonds.   The reaction is as follows:

CH3CH2OH + NAD+ ↔ CH3CHO + NADH + H+, or
ethanol + NAD+ ↔ acetaldehyde + NADH + hydrogen ion.

Ethanol to acetaldehyde

Ethanol is converted to acetaldehyde by stripping two hydrogen atoms. Grey = carbon, red = oxygen, white = hydrogen.  Click to enlarge.

Another 10-20% of ethanol is metabolized with the cytochrome P450 enzyme complex (CytP450 reductace, aka CYP2E1).  This reaction is typically much slower, requiring a higher ethanol concentration before it can start, hence why it is responsible for less ethanol breakdown.  This reaction looks much the same as before, but requires a slightly different helper molecule, NADP (nicotinamide adenine dinucleotide phosphate).  It too exists in both reduced and oxidized states, NADPH and NADP+, respectively.  Again, acetaldehyde is the product:

CH3CH2OH + NADPH + H+ + O2 ↔ CH3CHO + NADP+ + 2H2O, or
ethanol + NADPH + hydrogen ion + oxygen ↔ acetaldehyde + NADP+ + water.

Finally, a relatively minor reaction involves the catalase enzyme.  The contribution of this enzyme is only significant in a fasted (starving) state.  As before, acetaldehyde results:

CH3CH2OH + H2O2 ↔ CH3CHO +  2H2O, or
ethanol + hydrogen peroxide ↔ acetaldehyde + water.

The body, hard at work, has now converted the toxic ethanol to acetaldehyde, which in turn must also be dealt with.

(2) Acetaldehyde to Acetate and beyond

Unfortunately, acetaldehyde is also toxic, partly because it is a reactive oxygen species (ROS) which can cause cellular damage.  D’Oh!  But fear not, the body has the answer: the aldehyde dehydrogenase (ALDH) enzyme.  This enzyme catalyzes the reaction of acetaldehyde to an acetate.  Finally, something non-toxic!  The reaction is as follows:

CH3CH2OH + NAD+ + H2O ↔ CH3COO + NADH + 2H+, or
acetaldehyde +  NAD+ + water ↔ acetate ion + NADH + hydrogen ions.

acetaldehyde to acetate

Acetaldehyde is converted to acetate, an ion of acetic acid, by exchanging a hydrogen for an oxygen atom. Grey = carbon, red = oxygen, white = hydrogen.  Click to enlarge.

Acetate, a charged ion of acetic acid, leaves the liver where is is taken up by the heart, brain, and muscle tissue.  Notice that one of the oxygen atoms cannot form the two bond it likes: the right carbon has two bonds with one oxygen and one bond with the left carbon,  so only has one bond left to form with the other oxygen.  Acetic acid would have a hydrogen bonded to one of the oxygen atoms to balance it out; without it, the molecule is a negatively charged ion.

After another reaction catalyzed by the acetyl-CoA synthetase enzyme, acetate becomes acetyl-CoA, a larger molecule composed of one molecule each of acetate and CoA (co-enzyme A), not shown here.  Again, the enzyme name says it all: acetyl-CoA is synthesized by this enzyme.  At this point, it can enter in the tricarboxylic acid cycle (aka Krebs cycle, aka citric acid cycle) and be made into usable energy for the body, or act as a precursor to fatty acid or cholesterol biosynthesis.  In other words, its finally in a form that the body can use!

Loose Ends

There are a few other minor pathways for alcohol to be processed.  The above pathways were all “redox” reactions, a general term for any reaction involving the exchange of electrons to oxidize or reduce the reactive species, but there are a few non-redox reaction paths.  An example redox reaction you are likely familiar with is rust: iron is oxidized and losses electrons to form rust, aka “iron oxide.”

As you might imagine, the human body is a wonderfully complex machine, capable of great things.  But, we must treat it right; its worth taking a moment sometimes to ponder what is actually going on, and how to act responsibly to keep ourselves well.  Even if you didn’t understand every word of the above, I hope you at least come away with some appreciation for just one minor component of what the body does every day, unsung and overlooked, to keep you going.

[2014.05.09 UPDATE: See this post for an overview of how yeast produces ethanol.]

[Atomic model source data from as .pdb files, and rendered in Mathematica as ball-and-stick models.  The acetate ion was originally given as acetic acid from which the number 5 hydrogen was removed.  Information for this post comes mainly from the Oklahoma University “Chemistry of Beer” MOOC, Health Impact of Alcohol unit, posted 24 Jan 2014.]

– Dennis,
Life, Fermented


About Dennis
Home brewer, home chef, garage tinkerer. Author of Life Fermented blog.

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