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I. Chemical properties of the alcohol that is in
beer (and other alcoholic beverages)
II. A few preliminaries about Blood Alcohol
Concentration (BAC)
III. The enzyme‐catalyzed reactions that are
responsible for processing the alcohol
IV. A few loose ends and a summary
Ethanol: the Alcohol in Beer
Ethanol (CH3CH2OH) is introduced
into beer through the action of yeast
Ethanol (EtOH) is a relatively small
(MW = 46), amphiphilic molecule that
forms hydrogen‐bonding interactions
with water; EtOH is miscible in water
(its solubility in water is sometimes
indicated as: H2O)
EtOH passes through cell membranes
and penetrates the blood‐brain barrier
Blood Alcohol Concentration (BAC)
Several factors determine what a person’s BAC will be
after he or she consumes an alcoholic beverage. Some of
of these factors include:
1) how rapidly the alcoholic beverage was consumed
2) how much food the person has in their stomach
3) the size of the person
4) how rapidly a person is able to metabolize the EtOH
BAC cont’d
Because enzyme parameters such as Km (which we will discuss
shortly) are given in terms of concentration such as millimolar
(mM), but alcohol concentrations are typically given in terms of
percent volume (e.g., 6 % (v/v)), it is important for you to be able
to make some basic conversions so that you can answer
questions such as:
What is the millimolar concentration of alcohol in the aqueous
portion of a human body after a person has consumed a 12 oz.
beer that contains 6% (v/v) alcohol? Assume the alcohol is fully
distributed and has not begun to be metabolized or excreted.
Hint: the human body contains approximately 40 L of water.
Please note that there are several ways to solve this problem, but
you might want to look up the density of EtOH
Where Ethanol Is
Metabolized
The liver is the primary
site of EtOH metabolism
Some EtOH metabolism
also occurs in the gastro‐
intestinal tract, pancreas,
and brain
Three enzyme systems
are responsible for the
metabolism of EtOH http://education.yahoo.com/reference/gray
/illustrations/figure?id=1224
The Three Enzyme Systems That
Metabolize Ethanol
1) Alcohol Dehydrogenase (ADH) and Aldehyde
Dehydrogenase (ALDH); processes 80 – 90% of EtOH
2) Cytochrome P450 Enzyme Complex: CytP450
Reductase and CYP2E1; processes 10 – 20% of EtOH
3) Catalase; minor processing except in the fasted
state
Alcohol Dehydrogenase (ADH)
H O
H
H C H C
C OH C H
H H
H H
+ +
3 2 3
Ethanol Acetaldehyde
ADH is found in the cytosol of hepatic cells; many isoforms
The NAD+ and NADH stand for nicotinamide adenine
dinucleotide, oxidized and reduced forms, respectively
The acetaldehyde that is produced is toxic, hence the
need for the ALDH reaction
Aldehyde Dehydrogenase (ALDH)
There are cytosolic and mitochondrial forms of ALDH
Similar to ADH, ALDH also converts NAD+ to NADH as
it converts the substrate (acetaldehyde) to the product (acetate)
The acetate that is produced can be metabolized further
to CO2 and H2O, or it can serve as a precursor for fatty
acid biosynthesis
Why do we write “NADH” or “NAD+” rather
than show the structures?
Cytochrome P450 (CYP2E1)
CYP2E1 located in the lumen of the endoplasmic
reticulum (ER) of cells; it uses a heme cofactor
CYP2E1 has a higher Km for EtOH than does ADH; thus
CYP2E1 doesn’t “come into play” until [EtOH] is relatively
high
What is Km and how does this concept help us under‐
stand why ADH metabolizes most of the EtOH?
Km is the substrate concentration
that allows the enzyme to achieve
half of its maximal velocity (Vmax)
Vmax [S]
v
K m [S]
Catalase
Catalase is found in peroxisomes; similar to CYP2E1,
catalase also contains a heme cofactor
As noted, this reaction plays a very minor role in EtOH
metabolism except in the fasted state
The Fate of Acetate
Much of the acetate that is formed as a result of the
ALDH reaction leaves the liver; it can then be taken up
by the heart, brain, and skeletal muscle where it is further
metabolized, initially by the acetyl‐CoA synthetase reaction
The acetyl‐CoA produced as a result of the acetyl‐CoA
synthetase reaction can enter the Tricarboxylic Acid (TCA)
cycle, where it can be further metabolized into H2O and CO2, or
it can serve as a precursor for fatty acid biosynthesis and
cholesterol biosynthesis
A Few Loose Ends and a Summary
There are a few nonoxidative pathways, but we opted not to
cover these.
The CYP2E1 reaction can generate reactive oxygen species
(ROS) that can damage cells by forming, for example, adducts
with proteins; acetaldehyde can also form adducts with proteins.
The liver is the 1 organ that metabolizes EtOH; ADH is the
1 enzyme that reacts with EtOH, but CYP2E1 and catalase also
play a role. The ALDH reaction converts toxic acetaldehyde to
acetate, which can be broken down further to CO2 and H2O.
Both the ADH and ALDH reactions form NADH; please
keep this in mind as we will revisit this cofactor several
times.
If You Are Curious…
Pennington, E. “Ethanol Metabolism”
http://cnx.org/content/m38478/latest/.
Zakhari, Samir. 2006. “Overview: How Is Alcohol
Metabolized by the Body?” Alcohol Research
& Health 29 (4).