ALCOHOL METABOLISM

2.  Alcohol (ethanol or ethyl alcohol) is readily
absorbed by the stomach & intestine.
 Only 1% of the alcohol consumed is excreted
through lungs, urine & sweat.
 Major fraction of the alcohol is oxidized in
liver.
 Alcohol gets oxidized in the liver by alcohol
dehydrogenase to acetaldehyde.

3.  It is an NAD+ dependent cytoplasmic enzyme.
 It oxidizes ethanol to acetaldehyde.
 ADH is a dimer & has 6 isoenzymes.
 In some individuals the enzyme is mutated.
 In such individuals, alcohol metabolism is
slower & even small quantity of alcohol may
produce symptoms of intoxication.

4.  Acetaldehyde is further oxidized to acetate by
a mitochondrial NAD+ dependent enzyme
 The acetate is then converted to acetyl CoA.
 The activity of ADH is more than aldehyde
dehydrogenase.
 Acetaldehyde accumulates in liver.
 Aldehyde is toxic, excess may lead to cell
death.

6.  It is another mechanism of detoxification of
alcohol.
 It is cytochrome P450 dependent & is inducible.
 Ethanol can be oxidized in liver microsomes to
acetaldehyde by a mixed function oxidase.
 The electron donors are ethanol & NADPH by
which O2 is reduced to water.

7.  MEOS is part of the superfamily of
cytochrome P450, all of which catalyze similar
reactions.
 About 10 gene families & 100 different
cytochrome P450 molecules are available.
 The isoenzyme with highest activity towards
ethanol is designated CYP2E1 (2 refers to the
gene family, E refers to the subfamily & 1
refers to the particular enzyme).

8.  The metabolism of alcohol (by both
dehydrogenases) involves the consumption
of NAD+ & consequently a high NADH/NAD+
ratio.
 This is mostly responsible for the metabolic
alterations observed in alcoholism.

9.  Lactic acidosis:
 High concentration of NADH favours the
conversion of pyruvate to lactate which may
lead to lactic acidosis.
 Hypoglycemia:
 Deficiency of pyruvate leads to inadequate
formation of oxaloacetate.
 This results in depression of gluconeogenesis,
leading to hypoglycemia

10.  Reduced oxaloacetate, decreased pyruvate &
high NADH, causes suppression of TCA cycle.
 Acetyl CoA is accumulated, which favors
ketogenesis.
 Increased level of acetyl CoA causes
increased fatty acid synthesis; but fatty acid is
not oxidized.
 Fat is accumulated in liver, resulting in fatty
liver.

11.  Increased concentration of serum uric acid
due to its reduced excretion is observed in
alcoholism.
 This is due to lactic acidosis.
 Alcohol causes CNS depression by inhibiting
excitatory receptors (N-methyl aspartate
receptors) & by potentiating inhibitory
neurotransmitter (GABA) receptors.

12.  Alcoholism and liver:
 Accumulation of fat in liver cells leading to
fatty liver.
 Accumulated toxic effect of acetaldehyde
leads to cellular death & replacement by
fibrous tissue.
 Fibrosis of liver is called Cirrhosis.
 When liver functions are reduced hepatic
coma results.

13.  Alcoholism and Nervous Systes:
 In chronic alcoholics, the brain ventricles are
enlarged, neurons are lost, neuro-
degenerative changes.
 In alcoholics, combined thiamine deficiency
leads to Wernick's disease.
 Aldehyde inhibits pyridoxal phosphate;
neuritis is very common in alcoholics.

14.  Alcohol & Cardiovascular System:
 Mild alcohol intake (red wine less than 20 mg
per day) will marginally elevate HDL & reduce
the risk for myocardial infarction to a certain
extent.
 A small percent of alcohol is eliminated
through lungs.
 Lungs also share the deleterious effects of
alcohol.

15.  Textbook of Biochemistry-U Satyanarayana
 Textbook of Biochemistry-DM Vasudevan