Ethanol Metabolism
Rhea Andrea Flores Uy
Alcohol
• Ethanol is passively absorbed by simple
diffusion into enterocyte
• Ethanol metabolism occurs primarily in
the liver, but 10-30% is estimated to
occur in the stomach.
• For the average person, the liver can
metabolize the amount of ethanol in one
drink per hour.
Depends on rate of stomach emptying
Absorbed readily by simple diffusion (no digestion
needed)
Alcohol
Absorption
Higher proof → faster absorption
Wine is faster absorbed than liquor which is faster
than beer
Food slows absorption from the stomach
Controlled by genetic factors; such as variations in
enzymes that break down alcohol
Environmental factors ; such as amount of alcohol an
individual consumes
Alcohol
Metabolism
Higher proof → faster absorption
Wine is faster absorbed than liquor which is faster
than beer
Food slows absorption from the stomach
Oxidative Metabolism
Alcohol Dehydrogenase and
Aldehyde dehydrogenase
(ADH & ALDH)
➢ Alcohol is passed through the liver by the
circulating blood, it is acted upon by ADH
present in the liver cells
➢ The alcohol molecule is converted by this action
to acetaldehyde
➢ Acetaldehyde is immediately acted upon by
another enzyme, aldehyde dehydrogenase, and
converted to acetate
➢ Most enters the bloodstream and is ultimately
oxidized to carbon dioxide and water
COENZYME:
❑nicotinamide adenine dinucleotide (NAD)
❑RATE LIMITING STEP ON ALCOHOL
METABOLISM
Microsomal ➢ An alternate pathway of ethanol metabolism that
occurs in the smooth endoplasmic reticulum
➢ MEOS activity increases after chronic alcohol
Ethanol consumption.
➢ The MEOS pathway requires the CYP2E1 enzyme,
part of the cytochrome P450 family of enzymes, to
Oxidizing convert ethanol to acetaldehyde
➢ Ethanol’s affinity for CYP2E1 is lower than its affinity
System for alcohol dehydrogenase
• Acetaldehyde has the capacity to bind to
proteins such as enzymes, microsomal
proteins, and microtubules.
• It also forms adducts with the brain signaling
chemical such as dopamine to form
salsolinol
• which may contribute to alcohol dependence
• Forms adducts with DNA to form
carcinogenic DNA adducts such as 1,N2-
propanodeoxyguanosine.
• Formation of protein adducts in hepatocytes
impairs protein secretion, which has been
proposed to play a role in enlargement of
the liver (hepatomegaly).
❖Proteins found in the membranes surrounding the red blood
cells (i.e., erythrocytes).
❖Lipoproteins that consist of a protein and a fat component
and which are associated with the risk of heart disease.
❖Tubulin, a protein found in cell structures called microtubules
that are essential for cell division and protein transport within
cells.
❖Hemoglobin, which is crucial for oxygen transport by the
erythrocytes.
❖Albumin, which is a protein found in the blood.
❖Collagen, the major protein in
connective tissue.
❖Cytochrome enzymes, such as CYP2E1,
which play a role in the metabolism of
ethanol and many other substances.
• Acetate is not an inert product; it
increases blood flow into the liver and
depresses the central nervous system,
as well as affects various metabolic
processes (Israel et al. 1994).
• Acetate also is metabolized to acetyl
CoA, which is involved in lipid and
cholesterol biosynthesis in the
mitochondria of peripheral and brain
tissues.
• It is hypothesized that upon chronic
alcohol intake the brain starts using
acetate rather than glucose as a source
of energy.
Non - Oxidative Metabolism
➢ Fatty acid ethyl ester synthases catalyze the reaction between ethanol
and a fatty acid to produce a fatty acyl ester
➢ These synthases are present in most tissues, especially the liver and
pancreas,.
➢ These esters are synthesized in the endoplasmic reticulum.
➢ Fatty acid ethyl esters can be toxic, inhibiting DNA and protein
synthesis.
➢PEth is formed by transphosphatidylation of
phospholipids with ethanol
➢PEth is detectable 2 h after acute ethanol intoxication
➢serve as biomarker of ethanol intake
Consequences of
Ethanol Metabolism
❖Alcohol consumption results in significant
hypoxia in those hepatocytes that are
located close to the vein where the
cleansed blood exits the liver (i.e., in the
perivenous hepatocytes) (Arteel et al.
1996).
❖The perivenous hepatocytes also are the
first ones to show evidence of damage from
chronic alcohol consumption (Ishak et al.
1991), indicating the potential harmful
consequences of hypoxia induced by
ethanol metabolism.
❖Changes in the cells’ redox state (i.e., in the ratio of
NADH to NAD+) as a result of ethanol metabolism
by ADH and ALDH, which results in production of
more NADH.
❖Acetaldehyde formation.
ROS ❖Induction of CYP2E1 at high alcohol levels.
❖Hypoxia related to alcohol metabolism.
❖Alcohol-induced damage to the mitochondria.
❖Activation of Kupffer cells.
❖Reduction of the levels of certain antioxidants
(e.g., mitochondrial and cytosolic glutathione).
❖Formation of the 1-hydroxyethyl radical mentioned
above.
Inebriation
- Intoxication
- Drunkenness
You feel giddy
You start to lose the thread of
Warning what you’re saying
signs You feel unsteady on your feet
You start seeing double.
