A mbbs 1st year presentation about alcohol metabolism that covers some about alcohols effect its elimination in body It's long term effect of body and internal redox environment created by it And lastly about methanol poisoning And it's treatment

1. ALCOHOL
METABOLISM
ROHIT KUMAR SAINI
1STYEAR MBBS
STUDENT

2. • Alcohol absorption starts from the stomach itself, but most of it is
absorbed by duodenum and jejunum
• Only 1% of the ingested alcohol is excreted through lungs

3. Fact affecting alcohol absorption
Absorption of alcohol from the duodenum and jejunum is more
rapid than from the stomach, hence the rate of gastric emptying
is an important determinant of the rate of absorption of orally
administered alcohol
. Alcohol crosses biologic membranes by passive diffusion, down
its concentration gradient.Therefore, the higher the
concentration of alcohol, the greater is the resulting
concentration gradient, and the more rapid is the…
Gastric emptying drugs increase the alcohol absorption
(renitidine, semitidine)

4. Alcohol metabolism: general principles
• The major enzyme system(s) responsible for the oxidation of
ethanol, ADH, and, to a lesser extent, the cytochrome P450–
dependent ethanol-oxidizing system, are present to the largest
extent in the liver. Liver damage reduces the rate of alcohol
oxidation and, hence, elimination from the body.
• Ethanol is a nutrient and has caloric value (about 7 kcal (29.3
kjoules)/g; carbohydrates and protein produce 4 kcal…

5. Kinetics of alcohol elimination in vivo
• Alcohol elimination was originally thought to be a zero-order
process, meaning that alcohol was removed from the body at a
constant rate, independent of the concentration of alcohol.
Because the Michaelis constant (K ) of most ADH isozymes for
ethanol is low (about 1 mM), ADH is saturated at low
concentrations of alcohol; hence, the overall elimination process
proceeds at maximal velocity and is independent of the alcohol
concentration. However, linearity is not observed at low…

6. ADH
• ADH is a nicotinamide adenine dinucleotide (NAD+) dependent
cytoplasmic enzyme that oxidizes ethanol to acetaldehyde .the enzyme
has two Zn atom per subunit
• Zn is crucial for protein stability
• ADH is a dimer and has 6 isoenzymes in some individuals enzyme is
mutated
•
C2H5OH
ALCOHOL
DEHYDROGENASE
CH3CHO
NAD+ NADH + H+

7. ADH (ALCOHOL DEHYDROGENASE)
•Mutation rate is more in orientals
•Women are unable to process alcohol at the same rate as the
men because the expression the enzyme is less in the women
•The level of activity depends on allelic diversity among the
people in such individuals alcohol metabolism id slower and
even small quantity of alcohol may produce symptoms of
intoxication
•Unlike humans ,yeast and bacteria don’t ferment glucose to
lactate .instead ,they ferment it to ethanol and CO2
Oriental means coming from or associated
with eastern Asia, especially China and
Japan.

8. ALDEHYDE DEHYDROGENASE
• Acetaldehyde is further oxidized to acetate by a mitrochondrial
NAD+ DEPENDENT enzyme the acetate is then converted to
acetyl coenzyme A the activity of ALCOHOL
DEHYDROGENAGE is more than ALDEHYDE
DEHYDROGENASE
•
CH3CHO CH3COOH
ALDEHYDE
DEHYDROGENASE
NAD+ NADH2+

9. ALDEHYDE DEHYDROGENASE
• So acetaldehyde accumulate in the liver . Acetaldehyde is toxic
,which in excess may lead to cell death
• Activity of aldehyde dehydrogenase is less in Indians ,when
compared to europeans
• There are 19 genes in humans related to ALDH

10. Microsomal ethanol oxidizing system
• MEOS is another mechanism of detoxification of alcohol
it is cytochrome P450 dependent and it inducible
•This accounts for metabolic tolerance of alcohol
observed in chronic alcoholics
•Ethanol can be oxidized in liver microsomes to
acetaldehyde by a mixed function oxidase

11. Microsomal ethanol oxidizing system
•The electron donors are ethanol and nicotinamide
adenine dinucleotide phosphate (NADPH) by which O2
is reduced to water
CH3CH2OH CH3CHO + 2H2O
NADPH NADP+

12. Hepatic redox state
•Because the ADH and ALDH2 reactions reduce NAD to
NADH, the cellular NAD /NADH redox ratio is reduced as
a consequence of ethanol metabolism.
• This reduction has profound effects on other liver
metabolic pathways that require NAD or are inhibited by
NADH. Because the ADH reactions occur in the cytosol,
the cytosolic NAD /NADH redox ratio is reduced.This
ratio is reflected by the pyruvate/lactate ratio .cause
lactic acidosis because high NADH favors pyruvate to
lactate

13. High NADH/NAD+ Pyruvate Lactate Lactic acidosis
Pyruvate
deficiency
Decreased
gluconeogenesis
Hypoglycemia
Decreased OAA
SuppressionTCA
Acetyl CO A
Accumulate Ketogenesis
Fatty acid synthesis
But not oxidizes then Fatty liver

14. Hepatic redox state
• Deficiency of pyruvate leads to inadequate formation of OAA .
This results in depression of gluconeogenesiss ,leads to
hypoglycemia
• Reduced OAA , pyruvate ,and high NADH couse suppression of
TCA cycle so ACETYL CO A which favors ketogenesis
• Increased acetyl-coa couse fatty acid synthesis but fatty acid is
not oxidized so resulting in fatty liver
• Also increase ROS ALSO couse CNS depression

15. Reoxidation of NADH generated by the
ADH reaction
• To maintain effective rates of alcohol oxidation by ADH, it is
important to regenerate NAD from the NADH produced by the
ADH reaction. Under certain conditions, the rate of oxidation of
alcohol is limited by the reoxidation of NADH.
• The major system for reoxidizing NADH is the mitochondrial
electron transfer system. By coupling NADH reoxidation to this
system, energy is produced from alcohol metabolism (7 kcal/g
ethanol)

16. Substrate shuttles
• Because intact mitochondria are not permeable to NADH, it is
necessary to transfer the reducing equivalents of NADH present
in the cytosol into the mitochondria by substrate shuttle
mechanisms.
• The 2 major substrate shuttles are the ά-glycerophosphate
shuttle and the malate-aspartate shuttle .The malate-aspartate
shuttle plays the major role in transferring reducing equivalents
into the mitochondria

17. ALDH DEFICIENCY
• When high level of acetaldehyde occurs in the blood ,facial
flushing ,palpitations, nausea and general “HANGOVER”
symptiOMS occurs .
• These symptoms are togheter known as “ALCOHOL FLUSING
REACTIONS ” OR “ORIENTAL FLUSHING SYNDROME”
• Menifested by slow aldehyde removal with low alcohol tolarence
• The patients show higher blood levels of acetaldehyde ,and
become violently ill upon consuming even small amount of of
alcohol

18. Methanol metabolism
Methyl alcohol or Methanol or MeOH is the simplest alcohol, consisting of a
methyl group linked to a hydroxyl group
Methanol is however far more toxic than ethanol.
Small amounts of methanol are found in normal, healthy individuals, about
4.5 ppm in the exhaled breath of subjects.This is produced from pectin in
fruit.
Methanol is produced naturally in the anaerobic metabolism of
certain bacteria found in the environment.

19. MethanolToxicity
As little as 10 mL of pure methanol can cause ricles are enlarged,
permanent blindness by destruction of the optic nerve, while 30 mL is
fatal.Toxic effects begin hours after ingestion, and antidotes can often
prevent permanent damage. Methanol can be fatal due to its CNS
depressant activity. Moreover, it is metabolized to formaldehyde by
the ADH in the liver.This formaldehyde is further converted to formic
acid (formate) by ALDH. Formate is toxic because it inhibits
mitochondrial cytochrome c oxidase, causing cellular hypoxia and
metabolic acidosis.

20. Methanol toxicity
Major toxicity manifestation is loss of vision. Decreased vision
may start as early as 12 hours after exposure.
This may be accompanied by vomiting, abdominal pain,
decreased consciousness. Long-term outcomes may include
blindness and kidney failure.
Death may occur even after drinking a small amount

21. Treatment
Early treatment increases the chance of a good outcome.The preferred
antidote is fomepizole.
If it is not available, ethanol can be used. Ethyl alcohol will competitively
inhibit methanol.
Ethanol will bind more effectively to the enzyme ADH, thus blocking the
metabolism of methanol.

22. Treatment
The remaining methanol is excreted by the kidneys, without
producing the toxic formic acid.
Additional treatment may include sodium bicarbonate for metabolic
acidosis, and hemodialysis to remove methanol and formate from the
blood.
Folic acid is also administered to enhance the metabolism of formate.

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