Part 3

CHO Metabolism ALCOHOL

Metabolism

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 ALCOHOL
A class of organic compounds containing hydroxyl groups (OH) e.g.
glycerol, methanol.
Alcohol in alcoholic beverages is ethyl alcohol (ethanol), a small molecule
with a hydrophilic -OH group and a hydrophobic CH3 CH2-
chain.

Glucose
Pyruvate decarboxylase
2 Pyruvate 2 Acetaldehyde
2CO2
2 NADH + H+
Ethanol fermentation: the Alcohol
production of ethanol by strains dehydrogenase
of yeast and other 2 NAD+
microorganisms from CHOs.
2 Ethanol 2
 ALCOHOL – ABSORPTION &
TRANSPORT

As it is small and lipid-soluble, alcohol passes through the cell

membrane quickly by simple diffusion.
STOMACH
About 20% of alcohol is absorbed from the empty stomach
(food delays gastric emptying and its absorption). The
stomach begins to break down alcohol with its alcohol
dehydrogenase enzyme.

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ALCOHOL – ABSORPTION & TRANSPORT
This action can reduce the amount of alcohol
entering the blood by 20%
Women have less of this enzyme compared
to men.

Type of food in the stomach

– does it have any effect on
alcohol intake?

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ALCOHOL – ABSORPTION &
TRANSPORT
SMALL INTESTINES
About 80% of alcohol is absorbed here. Alcohol-laden
blood is carried via the portal vein to the liver where it
is metabolized to acetyl CoA.

Alcohol that is not metabolized by the liver is

excreted in the sweat, urine, or given off in one’s
breath (the basis of the breathalyzer test).
Alcohol diffuses uniformly into all body water, both ECF
and ICF.

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Why do women get more intoxicated on
alcohol than men ?
1. Less total body water. Alcohol diffuses
uniformly into all body water, ICF and ECF. For
a same amount of alcohol, a women would
have higher levels in her blood than a man
2. Effects of gonadal hormones – still being
researched. Women are less able to predict
the effects of consuming a given amount of
alcohol – more susceptible just before
menstruation
3. Less stomach enzyme alcohol
dehydrogenase – more alcohol enters the
blood stream
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 2 pathways

ALCOHOL MICROSOMAL
DEHYDROGENASE ETHANOL
PATHWAY OXIDISING SYSTEM
(MEOS)
(CYTOSOL of liver
cells) (SMOOTH
ENDOPLASMIC
RETICULUM)-1/5th of
alcohol is oxidized here
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 Alcohol dehydrogenase
Acetaldehyde

NAD+ NADH + H+
CoA
NAD+
High doses of alcohol
MEOS NADH+
H+

Acetyl CoA
NADPH + H+ NADP
Note: Whenever body breaks down alcohol NAD+
diminishes and NADH accumulates 8
Alcoholism: Biochemical and Metabolic
Alterations

Excessive alcohol consumption may lead to

the following metabolic effects:
1. Acetaldehyde Toxicity
2. Elevated NADH:NAD+ ratio
3. Other Metabolic Effects

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 EFFECTS OF ALCOHOL METABOLISM

Acetaldehyde toxicity
• 30 times more toxic than alcohol, acetaldehyde forms cross-
links with cellular macromolecules like enzymes, impairing
their activity.
• Acetaldehyde damages liver cells. The wound-healing
response to this injury causes fibrous material to be
deposited (fibrosis), leading eventually to cirrhosis
(extensive/late stage scarring) and loss of liver function.

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EFFECTS OF ALCOHOL METABOLISM
Elevated NADH:NAD+ ratio  lactic acidemia
Whenever the body breaks down alcohol, NAD+ diminishes and
NADH accumulates.
Glucose

Glyceraldehyde 3-phosphate (G3P) (2)

2 NAD+
2 NADH
1,3-biphosphoglyceric acid (2)
Lactate
dehydrogenase
PYRUVATE (2) LACTATE (2)
2 NAD+
2 NADH + 2 NAD+
2 H+
2 NADH
Acetyl CoA(2) 11
 Lactic acidemia
(high blood lactate levels)
This causes a metabolic shift in the reaction favoring lactate
formation (uses NADH, generates NAD+). Build up of lactate
reduces the pH = acidemia/Lactic acidemia (can be life-
threatening).

NADH + H+ NAD+

PYRUVATE LACTATE
LDH

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EFFECTS OF ALCOHOL METABOLISM
ALCOHOL
DEHYDROGENASE
PATHWAY
Elevated NADH:NAD+
Ethanol
NAD+NADH
Acetaldehyde ratio  Fatty liver

NAD+NADH
MEOS
The accumulation of
PATHWAY NADH prevents the
entry of acetyl CoA into
Fatty Acetyl-CoA the TCA Cycle (as more
acids NADH will be
generated).
TCA Cycle Instead acetyl CoA is
NAD+ NADH channeled to fatty acid
Triglycerides
synthesis.
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EFFECTS OF ALCOHOL METABOLISM
Fatty liver Glucose

Dihydroxyacetone Glyceraldehyde 3-phosphate (G3P)

phosphate (DHAP) 2 NAD+
Glycerol 3-phosphate 2 NADH
dehydrogenase
NADH 1,3-biphosphoglyceric acid (2)
Glycerol 3-phosphate Lactate
dehydrogenase
PYRUVATE (2) LACTATE (2)
Glycerol 2 NADH + 2 NAD+
2 H+

The increased NADH:NAD+ ratio also favors the activity

of the enzyme glycerol 3-phosphate dehydrogenase
which leads to glycerol synthesis. Glycerol, together
with fatty acids make triglycerides. 14
EFFECTS OF ALCOHOL METABOLISM

Liver cells prefer fatty acids as their fuel. They also

package excess fatty acids into triglycerides and
transport them to other tissues (VLDL).
•In the presence of alcohol,
•alcohol gets oxidized first
•fatty acids are not packaged and transported out
•Fatty acids accumulate (fatty liver) damaging liver cells.

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EFFECTS OF ALCOHOLISM ON LIVER
Fatty liver Steatohepatitis
reversible (inflammation)

Cirrhosis:
Acute & chronic alcoholic
when extensive/late
hepatitis (inflammation)
stage scarring
(fibrosis) damages
the liver.
scarring This scarring
Jaundice, ascites, replaces healthy
hepatic tissue and prevents
encephalopathy, the liver from
cirrhosis
coma working normally.
Alcoholism will ultimately affect the Cirrhosis usually
liver’s functions e.g. activating vitamin develops after years
D, producing bile, gluconeogenesis,
protein synthesis, etc of liver inflammation.16
 OTHER METABOLIC EFFECTS

Alcohol generates free radicals while inhibiting G6PD activity. This

significantly reduces active glutathione, causing oxidative damage. It can
cause ethanol-induced hemolysis in G6PD deficient individuals.
Alcohol depresses the production of anti-diuretic hormone (ADH) by the
pituitary gland. Results in large amounts of urine (and minerals lost) 
dehydration.
By damaging the cells lining the GIT, alcohol affects the absorption of some
nutrients. It also impacts the utilization of nutrients by affecting their transport,
storage and excretion.
Other consequences : CNS, socio-economic, etc

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