The catabolism of heme is a vital biochemical pathway for B. Pharm students to master, linking pharmacology, physiology and clinical biochemistry. This introduction explains heme catabolism, key enzymes like heme oxygenase and biliverdin reductase, bilirubin formation and conjugation by UGT1A1, transport (albumin, MRP2), and clinical correlations such as jaundice, Crigler–Najjar and Gilbert syndromes. Understanding bilirubin types, laboratory tests (Van den Bergh reaction), and drug interactions that affect bilirubin metabolism is crucial for drug safety and therapy. Solid knowledge of this pathway aids interpretation of liver function tests and management of hyperbilirubinemia. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What is the immediate product formed when heme is cleaved by heme oxygenase?
- Biliverdin
- Bilirubin
- Protoporphyrin IX
- Urobilinogen
Correct Answer: Biliverdin
Q2. Which enzyme converts biliverdin to bilirubin?
- Biliverdin oxidase
- Biliverdin reductase
- Heme oxygenase
- UDP-glucuronosyltransferase (UGT1A1)
Correct Answer: Biliverdin reductase
Q3. Where does the initial heme catabolism (heme to biliverdin) primarily occur?
- Renal proximal tubule
- Splenic macrophages (reticuloendothelial system)
- Pancreatic acinar cells
- Hepatocyte smooth endoplasmic reticulum
Correct Answer: Splenic macrophages (reticuloendothelial system)
Q4. Which cofactor is required by biliverdin reductase for the reduction of biliverdin to bilirubin?
- ATP
- NADH
- NADPH
- FAD
Correct Answer: NADPH
Q5. Carbon monoxide produced during heme catabolism is generated by which enzymatic action?
- UGT1A1 conjugation
- Biliverdin reduction
- Heme oxygenase cleavage of heme
- Cytochrome P450 oxidation of bilirubin
Correct Answer: Heme oxygenase cleavage of heme
Q6. Which form of bilirubin is water-soluble and directly excreted into bile?
- Unconjugated bilirubin
- Conjugated (direct) bilirubin
- Delta bilirubin
- Free bilirubin (non-albumin bound)
Correct Answer: Conjugated (direct) bilirubin
Q7. Unconjugated bilirubin is transported in plasma primarily bound to which protein?
- Transferrin
- Albumin
- Haptoglobin
- Alpha-1 acid glycoprotein
Correct Answer: Albumin
Q8. UDP-glucuronosyltransferase (UGT1A1) catalyzes which reaction in bilirubin metabolism?
- Oxidation of bilirubin to biliverdin
- Conjugation of bilirubin with glucuronic acid
- Transport of bilirubin into bile canaliculi
- Reduction of heme to biliverdin
Correct Answer: Conjugation of bilirubin with glucuronic acid
Q9. Which clinical condition is caused by complete absence of UGT1A1 activity?
- Gilbert syndrome
- Crigler–Najjar syndrome type I
- Dubin–Johnson syndrome
- Rotor syndrome
Correct Answer: Crigler–Najjar syndrome type I
Q10. Dubin–Johnson syndrome is characterized by a defect in which step of bilirubin handling?
- Conjugation of bilirubin
- Hepatic uptake of unconjugated bilirubin
- Canalicular excretion of conjugated bilirubin (MRP2/ABCC2)
- Intestinal bacterial conversion of bilirubin
Correct Answer: Canalicular excretion of conjugated bilirubin (MRP2/ABCC2)
Q11. Which laboratory test distinguishes conjugated from unconjugated bilirubin by a direct color reaction?
- Serum transaminases
- Van den Bergh reaction
- Prothrombin time
- Serum albumin concentration
Correct Answer: Van den Bergh reaction
Q12. In hemolytic anemia, which bilirubin fraction is predominantly elevated?
- Conjugated bilirubin
- Unconjugated bilirubin
- Delta bilirubin
- Direct bilirubin bound to albumin
Correct Answer: Unconjugated bilirubin
Q13. Which product of intestinal bacterial metabolism of bilirubin is reabsorbed and can enter the enterohepatic circulation?
- Stercobilin
- Urobilinogen
- Biliverdin
- Conjugated bilirubin
Correct Answer: Urobilinogen
Q14. Phototherapy treats neonatal hyperbilirubinemia by converting unconjugated bilirubin into what type of product?
- Water-soluble photoisomers excretable without conjugation
- Conjugated bilirubin via UGT1A1 induction
- Biliverdin via oxidation
- Hemoglobin-bound bilirubin complexes
Correct Answer: Water-soluble photoisomers excretable without conjugation
Q15. Which isoform of heme oxygenase is inducible by oxidative stress and drugs?
- HO-1
- HO-2
- HO-3
- UGT1A1
Correct Answer: HO-1
Q16. Which genetic condition results in mild unconjugated hyperbilirubinemia, often stress-induced and benign?
- Crigler–Najjar syndrome type II
- Gilbert syndrome
- Dubin–Johnson syndrome
- Hemochromatosis
Correct Answer: Gilbert syndrome
Q17. Which transporter mediates the canalicular secretion of bilirubin glucuronides from hepatocytes?
- OATP1B1
- MRP2 (ABCC2)
- NTCP
- P-glycoprotein (MDR1)
Correct Answer: MRP2 (ABCC2)
Q18. Atazanavir causes hyperbilirubinemia by inhibiting which hepatic process?
- Heme oxygenase activity
- UGT1A1-mediated conjugation
- Canalicular excretion via MRP2
- Albumin synthesis
Correct Answer: UGT1A1-mediated conjugation
Q19. Which color change corresponds to biliverdin during bruises and heme breakdown?
- Yellow
- Green
- Brown
- Red
Correct Answer: Green
Q20. Which enzyme system provides electrons to heme oxygenase for heme degradation?
- Cytochrome c oxidase
- NADPH-cytochrome P450 reductase
- Glutathione reductase
- Peroxidase
Correct Answer: NADPH-cytochrome P450 reductase
Q21. In obstructive (cholestatic) jaundice, which bilirubin fraction is primarily elevated?
- Unconjugated bilirubin
- Conjugated bilirubin
- Delta bilirubin only
- Free bilirubin due to hypoalbuminemia
Correct Answer: Conjugated bilirubin
Q22. What is “delta bilirubin” clinically?
- Unconjugated bilirubin bound to albumin
- Conjugated bilirubin covalently bound to albumin
- Bilirubin glucuronide excreted in urine
- Biliverdin derivative in bile
Correct Answer: Conjugated bilirubin covalently bound to albumin
Q23. Which drug induces heme oxygenase-1 expression and can increase biliverdin/bilirubin formation?
- Statins (e.g., simvastatin)
- Glucocorticoids (e.g., dexamethasone)
- Heme or hemin therapy
- Metformin
Correct Answer: Heme or hemin therapy
Q24. Stercobilin, the brown pigment in feces, is produced from bilirubin metabolites in the:
- Kidney
- Intestine by bacterial oxidation of urobilinogen
- Liver via conjugation
- Pancreas through enzymatic cleavage
Correct Answer: Intestine by bacterial oxidation of urobilinogen
Q25. Which condition typically shows dark urine and pale stools due to impaired bile excretion?
- Hemolytic jaundice
- Obstructive (post-hepatic) jaundice
- Gilbert syndrome
- Crigler–Najjar syndrome type I
Correct Answer: Obstructive (post-hepatic) jaundice
Q26. What is the physiological significance of bilirubin as an antioxidant at low concentrations?
- It promotes lipid peroxidation
- It scavenges reactive oxygen species protecting cells
- It increases free radical generation
- It chelates iron preventing heme synthesis
Correct Answer: It scavenges reactive oxygen species protecting cells
Q27. Which transporter mediates hepatic uptake of unconjugated bilirubin or organic anions from blood?
- OATP1B1/OATP1B3 (organic anion transporting polypeptides)
- MRP2 (ABCC2)
- NTCP (sodium taurocholate co-transporting polypeptide)
- P-glycoprotein (MDR1)
Correct Answer: OATP1B1/OATP1B3 (organic anion transporting polypeptides)
Q28. Which newborn metabolic deficiency leads to severe unconjugated hyperbilirubinemia and risk of kernicterus due to absent UGT1A1?
- Gilbert syndrome
- Crigler–Najjar syndrome type I
- Dubin–Johnson syndrome
- Rotor syndrome
Correct Answer: Crigler–Najjar syndrome type I
Q29. Which color change in urine is expected when conjugated bilirubin is elevated in plasma?
- Clear and colorless urine
- Dark (tea-colored) urine due to conjugated bilirubin/urobilinogen
- Milky urine due to fat
- Red urine due to hemoglobinuria
Correct Answer: Dark (tea-colored) urine due to conjugated bilirubin/urobilinogen
Q30. Which reagent gives a positive direct reaction in the Van den Bergh test for conjugated bilirubin?
- Diazotized sulfanilic acid without solvent (direct)
- Diazotized sulfanilic acid only after adding alcohol (indirect)
- Biuret reagent
- Folin–Ciocalteu reagent
Correct Answer: Diazotized sulfanilic acid without solvent (direct)
Q31. Which of the following drugs can increase unconjugated bilirubin by displacing bilirubin from albumin binding sites?
- Phenylbutazone
- Albumin itself
- Vitamin C
- Insulin
Correct Answer: Phenylbutazone
Q32. In adults, increased serum unconjugated bilirubin with normal liver enzymes suggests which primary cause?
- Hepatocellular necrosis
- Hemolysis or reduced conjugation (e.g., Gilbert)
- Cholestasis due to bile duct obstruction
- Acute viral hepatitis
Correct Answer: Hemolysis or reduced conjugation (e.g., Gilbert)
Q33. Which enzyme deficiency impairs bilirubin conjugation leading to increased indirect bilirubin with normal bile excretion?
- UGT1A1 deficiency
- MRP2 deficiency
- Biliverdin reductase deficiency
- Heme oxygenase deficiency
Correct Answer: UGT1A1 deficiency
Q34. Which therapeutic agent is used to treat Crigler–Najjar syndrome type I by replacing deficient conjugation activity?
- Phototherapy only
- Liver transplantation
- Oral phenobarbital induction of UGT1A1
- UDCA (ursodeoxycholic acid)
Correct Answer: Liver transplantation
Q35. Bilirubin glucuronides are examples of which biochemical process that increases solubility?
- Oxidation
- Conjugation (phase II metabolism)
- Reduction (phase I metabolism)
- Hydrolysis
Correct Answer: Conjugation (phase II metabolism)
Q36. Which organ primarily excretes conjugated bilirubin into the intestinal tract?
- Lungs
- Liver via bile
- Kidney via glomerular filtration
- Pancreas via pancreatic juice
Correct Answer: Liver via bile
Q37. Which physiological state increases heme turnover and can raise unconjugated bilirubin transiently?
- Prolonged fasting
- Hemolysis (e.g., transfusion reaction)
- High protein diet
- Dehydration
Correct Answer: Hemolysis (e.g., transfusion reaction)
Q38. Which bacterial action in the gut converts conjugated bilirubin to urobilinogen?
- Deconjugation and reduction by intestinal bacteria
- Sulfation by colonic enzymes
- Glucuronidation by gut mucosa
- Oxidation by pancreatic enzymes
Correct Answer: Deconjugation and reduction by intestinal bacteria
Q39. Which clinical test is most sensitive for detecting mild unconjugated hyperbilirubinemia seen in Gilbert syndrome?
- Serum alkaline phosphatase
- Serum total bilirubin with fractionation and fasting provocation
- Serum amylase
- Serum creatinine
Correct Answer: Serum total bilirubin with fractionation and fasting provocation
Q40. Which of the following statements about bilirubin binding to albumin is correct?
- Conjugated bilirubin binds more tightly to albumin than unconjugated
- Unconjugated bilirubin is tightly bound to albumin and not dialyzable
- Albumin-bound bilirubin is water-soluble and easily excreted by kidney
- Binding prevents bilirubin from crossing the blood–brain barrier in neonates
Correct Answer: Unconjugated bilirubin is tightly bound to albumin and not dialyzable
Q41. Which pigment is responsible for the yellow discoloration of jaundice?
- Biliverdin
- Bilirubin
- Stercobilin
- Hemoglobin
Correct Answer: Bilirubin
Q42. Which of the following decreases bilirubin conjugation leading to increased unconjugated bilirubin levels?
- Induction of UGT1A1 by phenobarbital
- Inhibition of UGT1A1 by certain drugs (e.g., atazanavir)
- Enhanced MRP2 activity
- Increased hepatic uptake via OATP
Correct Answer: Inhibition of UGT1A1 by certain drugs (e.g., atazanavir)
Q43. Which clinical manifestation indicates bilirubin has crossed the blood–brain barrier in neonates?
- Hepatomegaly
- Kernicterus (bilirubin encephalopathy)
- Pruritus without neurological signs
- Isolated dark urine
Correct Answer: Kernicterus (bilirubin encephalopathy)
Q44. Which laboratory pattern is typical of Rotor syndrome compared to Dubin–Johnson?
- Elevated conjugated bilirubin with dark liver pigment deposition like Dubin–Johnson
- Elevated conjugated bilirubin without black liver pigment and with impaired hepatic storage
- Predominant unconjugated hyperbilirubinemia
- Markedly elevated transaminases with low bilirubin
Correct Answer: Elevated conjugated bilirubin without black liver pigment and with impaired hepatic storage
Q45. Which hepatic phase II enzyme family is primarily responsible for glucuronidation reactions including bilirubin?
- Sulfotransferases
- UDP-glucuronosyltransferases (UGTs)
- N-acetyltransferases (NATs)
- Glutathione S-transferases (GSTs)
Correct Answer: UDP-glucuronosyltransferases (UGTs)
Q46. A drug that induces UDP-glucuronosyltransferase activity would likely cause which effect on bilirubin?
- Increase unconjugated bilirubin
- Decrease unconjugated bilirubin by enhancing conjugation
- Block canalicular excretion of conjugates
- Increase heme oxygenase activity
Correct Answer: Decrease unconjugated bilirubin by enhancing conjugation
Q47. Which of the following is a direct antioxidant action attributed to bilirubin at physiological levels?
- Pro-oxidant lipid peroxidation induction
- Scavenging of peroxyl radicals preventing oxidative damage
- Binding iron to promote Fenton reactions
- Stimulating NADPH oxidase to produce superoxide
Correct Answer: Scavenging of peroxyl radicals preventing oxidative damage
Q48. Which test result suggests a predominantly hemolytic cause for jaundice?
- High conjugated bilirubin with pale stools
- Elevated indirect bilirubin, increased LDH, reticulocytosis
- Very high alkaline phosphatase with pruritus
- Low urobilinogen in feces
Correct Answer: Elevated indirect bilirubin, increased LDH, reticulocytosis
Q49. Which enzyme deficiency would directly reduce production of biliverdin from heme?
- Bilirubin oxidase
- Heme oxygenase
- Biliverdin reductase
- UGT1A1
Correct Answer: Heme oxygenase
Q50. Which metabolic fate accounts for the majority of bilirubin elimination in humans?
- Renal excretion of unconjugated bilirubin
- Biliary excretion as bilirubin glucuronides and conversion to stercobilin in feces
- Metabolism to biliverdin and excretion in sweat
- Reabsorption and storage in adipose tissue
Correct Answer: Biliary excretion as bilirubin glucuronides and conversion to stercobilin in feces
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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