Free Radicals, Antioxidant Defence and Xenobiotic Metabolism MCQs

Biochemistry · 51 free questions with answers & explanations.

1. Paracetamol (acetaminophen) hepatotoxicity occurs at overdose. The toxic metabolite NAPQI is formed by which CYP450 enzyme, and its detoxification requires:
2. Superoxide dismutase (SOD) catalyses dismutation of superoxide radicals. The mitochondrial isoform of SOD (MnSOD) requires which metal cofactor, and what product is formed?
3. Isoniazid (INH) is metabolised primarily by N-acetyltransferase 2 (NAT2). A patient is a slow acetylator. Which adverse effect is they at GREATEST risk of, and why?
4. Lipid peroxidation chain reaction is initiated by reactive oxygen species. The chain-terminating antioxidant that donates a hydrogen atom to lipid peroxyl radicals and is regenerated by vitamin C is:
5. Paracetamol (acetaminophen) hepatotoxicity at overdose doses is due to accumulation of which toxic metabolite, produced when glucuronidation and sulfation pathways are saturated?
6. Glutathione (GSH) is the primary intracellular antioxidant peptide. Which enzyme regenerates GSH from GSSG (oxidized glutathione), and what is the essential cofactor?
7. CYP1A1 is strongly induced by polycyclic aromatic hydrocarbons (PAH) from cigarette smoke via the aryl hydrocarbon receptor (AhR). What is the toxicological consequence of CYP1A1 induction?
8. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide (O2•−) to H2O2. Which metalloenzyme variant is located in the cytoplasm, and which is in the mitochondrial matrix?
9. A patient is prescribed isoniazid for tuberculosis. After 3 months, she develops peripheral neuropathy. CYP2E1-mediated oxidation of isoniazid produces a reactive intermediate. The antidote that prevents this toxicity by preventing isoniazid's inhibitory effect on pyridoxine phosphokinase is:
10. The hepatotoxicity of paracetamol (acetaminophen) overdose is mediated by a reactive intermediate. Which CYP450 isoform is PRIMARILY responsible for its conversion to the toxic metabolite NAPQI?
11. In the Phase II detoxification reactions, glucuronidation is the MOST quantitatively important conjugation reaction. The activated donor molecule for glucuronidation is:
12. Superoxide dismutase (SOD) catalyses the dismutation of superoxide radical. In humans, the cytosolic isoform of SOD contains which metal cofactors?
13. The Fenton reaction is a key source of highly reactive hydroxyl radicals in biological systems. Which ion is the MOST important catalyst in the Fenton reaction in vivo?
14. Paracetamol (acetaminophen) hepatotoxicity occurs when therapeutic dose is exceeded. The reactive metabolite responsible for hepatocellular necrosis is NAPQI (N-acetyl-p-benzoquinone imine). NAPQI is generated by:
15. A patient taking warfarin is prescribed rifampicin for tuberculosis treatment. The warfarin anticoagulant effect is markedly reduced. The biochemical mechanism is:
16. Superoxide dismutase (SOD) converts superoxide radical to hydrogen peroxide. The subsequent detoxification of H2O2 in erythrocytes primarily involves which enzymatic system?
17. Lipid peroxidation of polyunsaturated fatty acids (PUFAs) in cell membranes is a chain reaction. The specific initiating event that converts a PUFA to a lipid peroxy radical is:
18. Paracetamol (acetaminophen) overdose causes hepatotoxicity through NAPQI formation. NAPQI is formed by CYP2E1. The reason therapeutic doses of paracetamol are safe but overdose is toxic is:
19. Superoxide dismutase (SOD) catalyses the dismutation of superoxide to hydrogen peroxide. The type of SOD found in mitochondria (Mn-SOD) is particularly important because:
20. Phase II biotransformation reactions conjugate drugs/xenobiotics to endogenous molecules. Glucuronidation requires UDP-glucuronic acid. A newborn has physiological jaundice partly because:
21. A patient with G6PD deficiency develops hemolysis after eating fava beans. The key biochemical sequence linking G6PD deficiency to erythrocyte destruction is:
22. CYP3A4 is the most abundant hepatic CYP450 isoenzyme. Rifampicin markedly induces CYP3A4 via the pregnane X receptor (PXR). The consequence for a patient taking rifampicin together with oral contraceptives (ethinylestradiol) is:
23. Paracetamol (acetaminophen) hepatotoxicity occurs when the minor metabolic pathway producing NAPQI (N-acetyl-p-benzoquinone imine) overwhelms glutathione stores. Which CYP isoform is primarily responsible for NAPQI formation?
24. Superoxide dismutase (SOD) catalyses the reaction: 2O2•− + 2H+ → H2O2 + O2. The H2O2 produced must be further detoxified. Which enzyme and cofactor pair achieves this reduction to water in the mitochondrial matrix?
25. Phase II xenobiotic metabolism involves conjugation reactions that increase hydrophilicity for renal/biliary excretion. Which enzyme system conjugates bilirubin and many drugs with glucuronic acid in the hepatic endoplasmic reticulum?
26. G6PD deficiency predisposes patients to haemolytic anaemia upon oxidant exposure (primaquine, fava beans, infections). The underlying biochemical defect is inability to regenerate NADPH because G6PD is the rate-limiting enzyme of which pathway?
27. Rifampicin and St John's Wort both cause therapeutic failure of concurrently administered drugs (e.g., oral contraceptives, antiretrovirals) by which shared mechanism?
28. Paracetamol (acetaminophen) hepatotoxicity in overdose is due to accumulation of which reactive metabolite?
29. The primary intracellular antioxidant defence against hydrogen peroxide in erythrocytes is:
30. G6PD deficiency causes haemolytic anaemia upon exposure to oxidant drugs because:
31. Phase II biotransformation of xenobiotics involves:
32. Vitamin E (alpha-tocopherol) acts as a chain-breaking antioxidant by:
33. CYP3A4 is the most abundant hepatic CYP enzyme and is responsible for metabolising approximately 50% of drugs. Which drug is a potent inducer of CYP3A4?
34. Paracetamol (acetaminophen) hepatotoxicity results from saturation of glucuronidation and sulfation pathways, forcing excess drug through CYP2E1. Which toxic metabolite is generated and which endogenous molecule is depleted in its detoxification?
35. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide to hydrogen peroxide. Hydrogen peroxide is then detoxified by which enzyme systems, and what cofactor is critical for glutathione peroxidase activity?
36. Phase II drug metabolism (conjugation reactions) generally increases water solubility for renal excretion. Which phase II reaction is responsible for the metabolism of isoniazid (INH) and is genetically polymorphic, affecting drug toxicity?
37. Which free radical is the MOST reactive oxygen species (ROS) and is responsible for initiating lipid peroxidation chain reactions in biological membranes?
38. Acetaminophen (paracetamol) hepatotoxicity at overdose doses occurs because the major detoxification pathways are saturated. Which CYP450 enzyme produces the toxic intermediate, and what is that intermediate?
39. Superoxide dismutase (SOD) converts superoxide radical (O2•−) to hydrogen peroxide (H2O2). What enzyme then converts H2O2 to water in the liver cytoplasm, and what cofactor does it require?
40. A patient on rifampicin for tuberculosis is also taking warfarin. His INR drops significantly, requiring a warfarin dose increase. This interaction is BEST explained by:
41. In reperfusion injury following myocardial ischemia, massive superoxide generation occurs. The MOST dangerous free radical formed from superoxide in the presence of Fe2+ (Fenton reaction) is:
42. N-Acetylcysteine (NAC) is given in paracetamol (acetaminophen) overdose. Which mechanism explains its hepatoprotective action?
43. Superoxide dismutase (SOD) catalyses the dismutation of superoxide radical. Which statement correctly distinguishes the isoforms of SOD in human cells?
44. Phenobarbital is a classic inducer of cytochrome P450 enzymes. Through which nuclear receptor does phenobarbital-mediated CYP3A4/CYP2B6 induction primarily occur?
45. Glutathione S-transferase (GST) is a key Phase II detoxification enzyme. In which of the following conditions is the highest expression of hepatic GST desirable, and why?
46. Paracetamol (acetaminophen) hepatotoxicity in overdose is caused by the toxic metabolite NAPQI. This metabolite is generated by which cytochrome P450 enzyme, upregulated by chronic alcohol use?
47. Superoxide dismutase (SOD) catalyses the dismutation of superoxide radical. The reaction product that must then be removed by catalase or glutathione peroxidase is:
48. Glucose-6-phosphate dehydrogenase (G6PD) deficiency renders erythrocytes susceptible to haemolysis under oxidative stress. G6PD is critical because it is the ONLY source of which protective molecule in RBCs?
49. Phase II conjugation reactions in xenobiotic metabolism increase drug water-solubility for excretion. Which Phase II reaction conjugates bile acids, bilirubin, and many drugs using UDP-glucuronic acid?
50. Reperfusion injury after myocardial ischaemia is primarily mediated by reactive oxygen species. The enzyme responsible for the burst of superoxide generation immediately upon reperfusion is:
51. Which antioxidant vitamin is a lipid-soluble, chain-breaking antioxidant that donates a hydrogen atom to quench lipid peroxyl radicals in cell membranes, and is regenerated by vitamin C?