alcohol metabolism for first mbbs students

1. ALCOHOL METABOLISM
DR.VIDHYALOGINI ,BIOCHEMISTRY

6. 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.

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

8. 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.

10. It is another mechanism of detoxification of
alcohol.
It is cytochrome P450dependent &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.

11. MEOS is part of the superfamily of
cytochrome P450,all of which catalyze similar
reactions.
About 10gene families &100different
cytochrome P450molecules are available.
The isoenzyme with highest activity towards
ethanol is designated CYP2E1(2refers to the
gene family, Erefers to the subfamily &1
refers to the particular enzyme).

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

13. 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.
Thisresults in depression of gluconeogenesis,
leading to hypoglycemia

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

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

16. 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.

17. 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.

18. Alcohol &Cardiovascular System:
Mild alcohol intake (red wine less than 20mg
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.

19. The cause of the disorder is thiamine
(vitamin B1) deficiency.
Wernicke encephalopathy and (Wernicke–Korsakoff syndrome
(WKS)are most commonly seen in people with an alcohol use
disorder.