FEELING THE

EFFECTS OF
ALCOHOL QUICKLY?

THE REASON GOES
DEEPER THAN
YOU THINK! So how does your body
eliminate alcohol? Let’s take a
Sarah Rammal
Ever wondered why some of your friends
seem to be able to drink much more than
you without feeling the effects of alcohol
quickly? Why some of your friends faces
turn red after a few drinks? What’s so
different about them?
Science now has an answer and it’s
not only related to your gender or your
size. It’s in your genetic make-up! Our
genes determine the ways our bodies
break down alcohol in a process called
alcohol metabolism. But what is alcohol
metabolism, you might be wondering?
Well, it’s the way our bodies break down
the alcohol we drink and eliminate it
from our systems. Scientists have also
discovered that alcohol related problems
vary in each individual due to the
differences in alcohol metabolism that
can put people in a higher risk of alcohol’s
harmful effects.[1]
Do you want to know more? Read on!
look at the different pathways:
The Oxidative and Non-
Oxidative pathways.
After you have your first sip, the alcohol goes
through your digestive system and is
then absorbed in the bloodstream. Around
2-8% of alcohol is excreted through your
breath, urine or sweat. [1][2] The MAJORITY
of consumed alcohol is metabolised
(broken down) in the liver by an enzyme
called Alcohol Dehydrogenase (ADH) which
converts alcohol to Acetaldehyde and later to
acetate by the Acetaldehyde Dehydrogenase
enzyme (ALDH). This process is called the
Oxidative pathway. [10]
In addition to ADH, other enzymes, i.e:
Cytochrome P4502E1 (CYP2E1) and
Catalase, also participate in the production
of acetaldehyde from alcohol oxidation.
During high alcohol consumption, CYP2E1
increases the rate of alcohol clearance
which is accountable for the body’s
tolerance of alcohol consumption.
1
CYP2E1 also affects frequent alcohol
consumption in the sense that it leads to
higher acetaldehyde concentrations, and
decreased ALDH activity. Catalase is also
involved in the alcohol metabolism process.
It’s role is minor, however its role is boosted
when higher amounts of hydrogen peroxide is
present. Catalase may be another pathway for
alcohol oxidation in the brain where CYPE2E1
seem to be of lesser importance for alcohol
metabolism. But catalase’s exact role in
alcohol elimination is still a matter of debate. [8]
In the non –oxidative pathway, breakdown of
alcohol occurs in the organs that are most injured
by alcohol abuse. Studies have found that during the
non oxidative process of alcohol metabolism, alcohol
is broken down to fatty acid ethyl esters, (which is
the combination of a fatty acid with alcohol) found
in organs that lacking alcohol oxidative elimination
processes, such as the heart.[8] During the findings, it
was discovered that fatty acid ethyl esters form during
and shortly after alcohol ingestion in large quantities
in the liver, pancreas, brain and heart and stay stored
for a long time in fat tissues.[10] The findings have
suggested that because some of these organs do not
break down alcohol by the oxidative process, fatty acid
ethyl esters could play a role in organ damage caused
by large alcohol intake.[3][4]
Hang on! How does this all
relate to our genetics?
Well, since we’re all uniquely different and come
from different racial backgrounds, this means
that we have variations of genes and alleles (variants
or mutations of genes) that encode enzymes in
our bodies. Both ADH and ALDH exhibit genetic
polymorphism (variations) which affects the
frequency of breakdown of alcohol in the liver to
acetaldehyde, and of acetaldehyde to acetate. [11]
These genetic variations have been the subject
of many studies mainly the ADH1B and ADH1C
gene variants due to their possible role in the
development of alcohol abuse and alcoholism.[8]
ADH1B2, ADH1B3 and ADH1C1 variants reveal
a quicker alcohol metabolisation rate and are
believed to promote acetaldehyde build up.In most
populations, ADH1B*1 is the most prevalent
allele which is linked to the increased risk of
alcoholism.[8]
But up to 90% of people from Asian descent have
lower levels of alcoholism when compared with
other ethnicities and that is due to the ADH1B*2
allele. This allele codes for an enzyme with a
faster alcohol metabolisation rate which leads to
the accumulation of acetaldehyde thus causing
unpleasant symptoms[8] i.e: “Flush Syndrome”
which is the exhibition of intense facial flushing
in addition to headaches, nausea, vomiting, heart
palpitations and other physical unpleasantness
after a mild dose of alcohol.[5][6] Due to these
experienced symptoms, the ADH1B*2 allele protects
against alcohol abuse and alcoholism by deterring
those who have it from excessive drinking.[9]
Another example is the ADH1B*3 allele which exists
almost entirely in African Americans, Africans and
some percentage of the Native Americans. This
allele is linked to lower frequencies of excessive
drinking and alcohol abuse in Native Americans
and lower risk for the development of alcoholism
amongst African Americans.[8][9]
Also, it has been reported that ALDH2- a variant of
ALDH - is the most essential alcohol-metabolising
gene affecting susceptibility to alcoholism in
Asian populations. The predominance of the
ALDH2*2 allele is lower in alcoholics than in non-
alcoholics. However, this allele hasn’t been found
in Caucasian individuals.[11]
2
OK. Is there a way to treat
alcoholism in a similar fashion
to how our genes work?
An interesting way that alcoholism is treated is
by Antabuse, a drug made out of the compound
disulfiram. Now what’s so special about this drug? It
works by inhibiting acetyl dehydrogenase which in
turn increases acetaldehyde greatly. In other words,
this drug basically works like the enzyme that gives
the patient “Flush syndrome”, headaches, heart
palpitations, nausea and other unpleasant extreme
symptoms and makes the patient feel very sick.
This is the way the drug works by deterring them
from drinking alcohol.[8] Antabuse has harmful side
effects and should be monitored closely while on
this drug.[7] Large amounts of alcohol mixed with
Antabuse can lead to death.[4]
There you have it – you now know why some of
your friends can drink more, why some of them
blush red and what is happening to your body after
that first sip of your drink!
References
[1] A. Cederbaum, Clinics In Liver Disease 16 (2012).
[2]Alcohol Metabolism Part: Mechanisms Of Action 29
(2006).
[3] E. Laposata, L. Lange, Science 231 (1986).
[4] K. Anderson, How To Change Your Drinking, 1st ed.,
HAMS Harm Reduction Network, New York, NY, 2010.
[5] D. Agarwal, Pathologie Biologie 49 (2001).
[6] Y. Chen, G. Peng, M. Wang, T. Tsao, S. Yin, Chemico-
Biological Interactions 178 (2009).
[7] H. Kristenson, Acta Psychiatrica Scandinavica 86
(1992).
[8] E. Quertemont, Molecular Psychiatry 9 (2004).
[9] M. Y. Eng, S. E. Luczak, T. L. Wall, Alcohol Res Health 30
(2007).
[10] S. Mukherjee, OA Publishing London (2014).
[11] E. Borràs, C. Coutelle, A. Rosell, F. Fernández-Muixi,
M. Broch, B. Crosas, L. Hjelmqvist, A. Lorenzo, C. Gutiérrez,
M. Santos, M. Szczepanek, M. Heilig, P. Quattrocchi, J.
Farrés, F. Vidal, C. Richart, T. Mach, J. Bogdal, H. Jörnvall,
H. Seitz, P. Couzigou, X. Parés, Hepatology 31 (2000)
[12] Shutterstock, Stock Vector ID: 544426720, 2017.
Sarah Rammal is a student at UTS and is currently undertaking
a Bachelor of Medical Science degree.