Metabolism of xenobiotics

Q-1. Which of the following is not Phase-I reaction
a) Oxidation
b) Reduction
c) Hydrolysis
d) Conjugation

Answer: Conjugation
Explanation:
Phage-I Reaction:
Hydroxylation
Reduction
Deamination, de-halogenation, and de-sulfuration
Epoxidation and per-oxygenation
Important points:
In Phase-I, the major reaction involved is hydroxylation catalysed mainly by mono-oxygenase or CYP-450. Cytochrome P-450 mono-oxygenase is the main enzyme responsible for activation of xenobiotics.
Cytochrome-450 is located in the smooth endoplasmic reticulum or in mitochondria and considered as the most versatile bio-catalyst known.

Q-2. The main enzyme responsible for activation of xenobiotics is
a) Cytochrome P-450
b) Glutathione S-transferase
c) NADPH cytochrome P-450-reductase
d) Glucuronyl transferase

Answer: Cytochrome P-450
Explanation:
See above explanation.
Phase-II Reaction: Conjugation
Glucuronidation
Sulfation
Conjugation with glutathione
Acetylation
Methylation
Glucuronidation is probably the most frequent conjugation reaction.
Important point:
Purpose of two phase of metabolism of xenobiotics is to increase their water solubility (Polarity) and thus excretion from body.

Q-3. All are true about glutathione except: (AIIMS Nov 2008 and May 2008)
a) It converts hemoglobin to methemoglobin
b) It scavenges free radicals and superoxide ions
c) It is tri-peptides
d) It conjugates xenobiotics

Answer: It converts hemoglobin to methemoglobin
Explanation:
A number of potentially toxic electrophilic xenobiotics are conjugated to the nucleophilic GSH.
The enzyme catalyzing this reaction is called glutathione-S-transferase and present in high amounts in liver cytosol and in lower amount in other tissues.
GSH is an important defense mechanism against certain toxic compounds.
Important point:
Glutathione (GSH) is a tri-peptide consisting of Glutamic acid, cysteine and glycine.

Q-4. Which of the following enzymes are associated with breakdown of H2O2? (PGI May 2011)
a) Catalase
b) Oxidase
c) Peroxidase
d) Oxygenase
e) Hydrolase

Answer: a and c
Explanation:
Generation of H2O2:
Oxidase and super-oxide dismutase
Breakdown of H202:
Catalase and peroxidase

Q-5. H2O2 is beaked and formed by which of the following enzyme? (PGI June 2003)
a) Catalase
b) Oxidase
c) Peroxidase
d) Oxygenase
e) Hydrolase

Answer: a, b and c
Explanation:
See above explanation.

Q-6. What is metabolized like xenobiotics?
a) Myoglobin
b) Bilirubin
c) Biliverdin
d) Hemoglobin

Answer: Bilirubin
Explanation:
Bilirubin is metabolized like xenobiotics. It is conjugated with beta glucuronic acid in liver to convert a hydrophobic bilirubin to a hydrophilic one which is readily excreted in bile.

Q-7. Bile salts undergo xenobiotics
a) After conjugation with taurine and glycine
b) After conjugation with lysine
c) After conjugation with beta glucuronic acid
d) After conjugation with derived proteins

Answer: After conjugation with beta glucuronic acid
Explanation:
See above explanation.

Q-8. The conjugation of bilirubin to glucuronic acid in the liver
a) Converts a hydrophilic compound to a hydrophobic one
b) Converts a hydrophobic compound to a hydrophilic one
c) Enables the bilirubin molecules to cross the cell membrane
d) In increased during neonatal jaundice

Answer: Converts a hydrophobic compound to a hydrophilic one
Explanation:
See above explanation.