e

e
m

m
m
co

Free Radicals, Xenobiotics and Metabolism of Alcohol

  | 415

Conjugation with Glycine Metabolic Changes Following Ingestion of

Benzoic acid conjugated with Glycine to form Hippuric Alcohol
Acid (Benzoyl Glycine) High concentration of NADH leads to high NADH/NAD+
ratio. This is the basic cause of all metabolic alteration in
Conjugation with Glutamine alcoholism.
Phenyl Acetic Acid is conjugated with Glutamine to form • Favor conversion of Pyruvate to Lactate ( This leads
Phenyl Acetyl Glutamine.
m

to Lactic acidosis)
• Deficiecy of Pyruvate leads to deficiency of Oxaloac-
co

METABOLISM OF ALCOHOL etate. This leads to decrease in Gluconeogenesis

Topics included
• Metabolism of Alcohol
• Metabolic alterations following ingestion of alcohols
Metabolism of Alcohol
• NAD+ Dependent Cytoplasmic Alcohol Dehydro-
genase oxidises Ethanol to Acetaldehyde.
• Acetaldehyde is further oxidized to Acetate by
mitochondrial NAD+ dependent Aldehyde Dehy-
drogenase. Activity of Alcohol Dehydrogenase is
m
which causes hypoglycemia.
• Decreased availability of NAD+ and decreased
Oxaloacetate lead to decreased TCA Cycle leads to
accumulation of Acetyl CoA
• Accumulation of Acetyl CoA leads to Ketogenesis
and Lipogenesis and Fatty Liver.
• Lactic Acidosis leads to decreased Uric Acid excretion
and hence gout.
Protective Mechanism of Microsomal Ethanol Oxidizing System
(MEOS)

• Some metabolism of ethanol takes place via a cytochrome P450-

more than Aldehyde dehydrogenase. dependent microsomal ethanol oxidizing system (MEOS) involving
co

NADPH and O2.

• So, Acetaldehyde accumulates in the liver
• So NADH/NAD+ ratio is not altered hence account for metabolic
• Aldehyde is toxic and causes cell death. tolerance in chronic alcoholics.
• This system is inducible hence increases in activity in chronic
alcoholism.
• In some Asian populations and Native Americans, alcohol
consumption results in increased adverse reactions to
acetaldehyde owing to a genetic defect of mitochondrial aldehyde
dehydrogenase.
Fig. 18.4: Metabolism of alcohol

REVIEW QUESTIONS
m
co

Free Radicals 2. Most powerful chain breaking antioxidant:

1. Free radical with highest activity: a. Glutathione peroxidase
a. O2– b. Alpha tocopherol
b. OH• c. Superoxide dismutase
c. Hypochlorite d. Vitamin C
d. Peroxynitrite Ans. b. Alpha tocopherol
Ans. b. OH•
3. Enzyme which catalyze the reaction H2O2 give
Points to Remember H2O + O2:
• Most powerful oxygen free radical is Hydroxyradical a. Catalase
(OH•)Q
b. Glutathione reductase
m

• Least powerful Reactive Oxygen species is Hydrogen

c. Glutathione peroxidase
co

peroxide (H2O2).
d. Glutathione s transferase
• Precursor of all reactive Oxygen species is Superoxide
radical (O2– ) Ans. a. Catalase
 e

e
m

m
m
co

416 |  
Self Assessment and Review of Biochemistry

Catalase b. Decreased lactate/Pyruvate ratio

It is a hemoprotein with four hemegroups. Causes decom- c. Inhibition of Gluconeogenesis
position of peroxides to yield water and oxygen. Highest d. Stimulation of fatty acid oxidation
concentration of Catalase is present in Peroxisomes.
Ans. a. Increased NADH/NAD+ ratio
         Catalase
2H2O2 2H2O + O2 High concentration of NADH leads to high NADH/NAD+
m

ratio. This is the basic cause of all metabolic alteration

Remember
co

H2O2 is not free radical but can generate free radical. in alcoholism.

4. Which of the following is not a free radical?

a. Hydroxyl radical 6. Best explained pathogenesis of fatty liver in
b. Hydrogen Peroxide alcoholic liver disease: (Jipmer 2013)
c. Superoxide a. Increased hydrolysis of fat from adipocytes
d. O2● b. Decreased synthesis of fatty acids
Ans. b. Hydrogen Peroxide.
c. Decreased [NADH]/[NAD+] ratio
It is a reactive oxygen species, not a free radical.
d. Impaired beta oxidation of fatty acids
Alcohol Metabolism Ans. d. Impaired beta oxidation of fatty acids
5. Toxicity of Ethanol is due to: (Jipmer 2012)
m

Impaired beta oxidation leads to increased TAG in the

a. Increased NADH/NAD+ ratio
co

liver, which leads to fatty liver.

m
co
m
co