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Reactive Oxygen Species and Antioxidant Defense

Tier 2 · #17 of 33 · high yield · topic 4.7 — every high-yield fact from the book chapter, exam-ready.

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  1. Front
    What is a reactive oxygen species (ROS) ?
    Back
    Any oxygen-containing molecule that is more chemically reactive than molecular O2 .
  2. Front
    What feature makes most ROS free radicals ?
    Back
    An unpaired electron .
  3. Front
    Which ROS produced by partial reduction of O2 is NOT a free radical ?
    Back
    Hydrogen peroxide (H2O2) — it has no unpaired electrons .
  4. Front
    The 1-electron reduction of O2 produces ______.
    Back
    Superoxide (O2•−) .
  5. Front
    The 2-electron reduction of O2 produces ______.
    Back
    Hydrogen peroxide (H2O2) .
  6. Front
    The 3-electron reduction of O2 produces ______.
    Back
    The hydroxyl radical (•OH) .
  7. Front
    The 4-electron reduction of O2 produces ______.
    Back
    Water (H2O) .
  8. Front
    Which ROS is the primary one of the body and the starting point of the cascade?
    Back
    Superoxide (O2•−) .
  9. Front
    Where in the mitochondrial electron transport chain does superoxide form?
    Back
    Complex I and complex III (electrons leak onto O2 before reaching complex IV).
  10. Front
    Why is H2O2 able to spread oxidative damage far from its site of production?
    Back
    It diffuses freely across membranes .
  11. Front
    Which ROS is the most reactive and damaging in biology?
    Back
    The hydroxyl radical (•OH) .
  12. Front
    Is there an enzyme that directly scavenges the hydroxyl radical ?
    Back
    No — defense against •OH is entirely preventive (keep H2O2 low, keep free iron sequestered).
  13. Front
    Which enzyme (complex IV) carries out the 4-electron reduction of O2 to water in normal respiration?
    Back
    Cytochrome c oxidase .
  14. Front
    Write the Fenton reaction .
    Back
    Fe2+ + H2O2 → Fe3+ + •OH + OH−.
  15. Front
    Why is the Fenton reaction clinically dangerous?
    Back
    Fe2+ converts manageable H2O2 into the hydroxyl radical (•OH) , the most destructive ROS.
  16. Front
    What does the Haber-Weiss reaction do in the iron-radical cycle?
    Back
    Reduces Fe3+ back to Fe2+ using superoxide , regenerating the catalyst for the Fenton reaction .
  17. Front
    Net reaction of the Haber-Weiss cycle (iron-catalyzed)?
    Back
    O2•− + H2O2 → •OH + OH− + O2.
  18. Front
    In what oxidation state do ferritin and transferrin keep iron , and why?
    Back
    Fe3+ (sequestered), to prevent it from driving the Fenton reaction .
  19. Front
    Which conditions amplify oxidative damage by releasing free iron ?
    Back
    Hemolysis , iron overload , and ischemia-reperfusion .
  20. Front
    What is the largest background source of ROS in the body?
    Back
    The mitochondrial electron transport chain (leaks at complex I and III ).
  21. Front
    Roughly what fraction of mitochondrial O2 consumption becomes superoxide under normal conditions?
    Back
    About 1–3% .
  22. Front
    Which enzyme is activated in the phagocyte oxidative (respiratory) burst?
    Back
    NADPH oxidase .
  23. Front
    What does NADPH oxidase produce, and from what electron source?
    Back
    Superoxide , by transferring electrons from cytosolic NADPH to O2 ( NADPH + 2O2 → NADP+ + H+ + 2O2•−).
  24. Front
    Which enzyme converts H2O2 to hypochlorous acid (HOCl) in phagocytes?
    Back
    Myeloperoxidase .
  25. Front
    A genetic defect in NADPH oxidase causes which disease?
    Back
    Chronic granulomatous disease (phagocytes engulf but cannot kill catalase-positive organisms).
  26. Front
    Why are peroxisomes rich in catalase ?
    Back
    Peroxisomal fatty acid oxidation generates H2O2 directly, so catalase neutralizes it in the same organelle .
  27. Front
    What is oxidative stress ?
    Back
    A disturbance in the balance between ROS production and antioxidant capacity , causing net oxidative damage.
  28. Front
    Lipid peroxidation of membrane PUFAs generates which secondary toxic aldehydes?
    Back
    Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) .
  29. Front
    Which DNA lesion from oxidation causes G→T transversions?
    Back
    8-hydroxyguanosine (8-OHG) .
  30. Front
    Which oxidized species is the key atherogenic agent in atherosclerosis ?
    Back
    Oxidized LDL .
  31. Front
    Which neurodegenerative disease involves oxidative damage to dopaminergic neurons in the substantia nigra ?
    Back
    Parkinson's disease .
  32. Front
    Write the reaction catalyzed by superoxide dismutase (SOD) .
    Back
    2 O2•− + 2H+ → H2O2 + O2 (a dismutation).
  33. Front
    What metal cofactor does the mitochondrial SOD isoform (MnSOD/SOD2) use?
    Back
    Mn2+ .
  34. Front
    What metal cofactor does the cytosolic SOD isoform (CuZnSOD/SOD1) use?
    Back
    Cu2+/Zn2+ .
  35. Front
    Why is the SOD step critical for stopping radical chain propagation?
    Back
    It converts a free radical (superoxide) into a non-radical (H2O2) .
  36. Front
    Write the reaction catalyzed by catalase .
    Back
    2 H2O2 → 2 H2O + O2 .
  37. Front
    Does catalase require an external electron donor?
    Back
    No — it uses one H2O2 as the donor and the other as the acceptor.
  38. Front
    In which organelle is catalase concentrated?
    Back
    Peroxisomes .
  39. Front
    Catalase vs glutathione peroxidase : which works best at HIGH H2O2 concentrations?
    Back
    Catalase (GPx handles low-to-moderate concentrations better).
  40. Front
    Write the reaction catalyzed by glutathione peroxidase (GPx) .
    Back
    H2O2 + 2 GSH → 2 H2O + GSSG .
  41. Front
    What trace element makes glutathione peroxidase reactive (it is a ______-protein)?
    Back
    Selenium ( GPx is a selenoprotein).
  42. Front
    In what cell compartments is GPx present, unlike catalase ?
    Back
    Both cytoplasm and mitochondria .
  43. Front
    Which H2O2 -degrading enzyme can also reduce membrane lipid peroxides (ROOH)?
    Back
    Glutathione peroxidase (GPx) : ROOH + 2 GSH → ROH + H2O + GSSG.
  44. Front
    In the GPx reaction, what is the electron donor and what is the electron acceptor?
    Back
    GSH is the electron donor ; H2O2 is the acceptor.
  45. Front
    Write the reaction catalyzed by glutathione reductase (GR) .
    Back
    GSSG + NADPH + H+ → 2 GSH + NADP+ .
  46. Front
    What is the exclusive source of the NADPH used to regenerate GSH ?
    Back
    The oxidative branch of the pentose phosphate pathway (via G6PD ).
  47. Front
    Which enzyme provides NADPH for glutathione regeneration in the red blood cell ?
    Back
    Glucose-6-phosphate dehydrogenase (G6PD) .
  48. Front
    What is favism ?
    Back
    Hemolytic anemia triggered by fava beans (or oxidant drugs) in G6PD-deficient patients.
  49. Front
    What is the most common human enzyme deficiency worldwide, and its inheritance?
    Back
    G6PD deficiency ; X-linked (predominantly affects males).
  50. Front
    In G6PD deficiency , why does H2O2 accumulate after an oxidant challenge?
    Back
    No NADPH can be regenerated → GSH can't be replenished → GPx loses its reductant.
  51. Front
    What are the denatured hemoglobin precipitates seen in G6PD-deficient red cells?
    Back
    Heinz bodies (visible on supravital staining).
  52. Front
    Which oxidant drugs can trigger hemolysis in G6PD-deficient patients?
    Back
    Primaquine , dapsone, and nitrofurantoin.
  53. Front
    Why are red blood cells uniquely vulnerable in G6PD deficiency ?
    Back
    They have no mitochondria , so the PPP is their only source of NADPH .
  54. Front
    Which most abundant intracellular antioxidant is present at millimolar concentrations in the cytoplasm ?
    Back
    Glutathione (GSH) .
  55. Front
    Which functional group on glutathione's cysteine donates the electron to a radical?
    Back
    The free thiol (–SH) group .
  56. Front
    Which is the major WATER-soluble antioxidant in plasma?
    Back
    Vitamin C (ascorbic acid) .
  57. Front
    What does vitamin C become after donating an electron to a radical?
    Back
    The relatively stable, unreactive ascorbyl radical (regenerated by NADPH or GSH ).
  58. Front
    Which is the major FAT-soluble antioxidant, found in membranes and lipoproteins?
    Back
    Vitamin E (α-tocopherol) .
  59. Front
    What is the specific role of vitamin E ?
    Back
    To interrupt lipid peroxidation chain reactions in membranes.
  60. Front
    How does vitamin E quench a lipid radical?
    Back
    It donates a hydrogen atom from its phenolic –OH group , forming the stable tocopherol radical.
  61. Front
    What is the order of the antioxidant regeneration chain from lipid radical back to glucose metabolism?
    Back
    Tocopherol radical → ascorbate (vitamin C) → GSH → NADPH (from the PPP) .
  62. Front
    Which antioxidant regenerates oxidized vitamin E at the membrane-water interface?
    Back
    Vitamin C (ascorbate) .
  63. Front
    Which vitamin A precursor antioxidant quenches singlet oxygen and peroxy radicals?
    Back
    Beta-carotene .
  64. Front
    Why is uric acid an unusually important plasma antioxidant in humans?
    Back
    Humans lack uricase , so plasma uric acid is high compared to other primates.
  65. Front
    Which plasma protein chelates copper to prevent it from driving Fenton -type reactions?
    Back
    Ceruloplasmin .
  66. Front
    Which enzyme deficiency causes erythropoietic protoporphyria (EPP) ?
    Back
    Ferrochelatase deficiency (protoporphyrin IX accumulates).
  67. Front
    In EPP , light-excited protoporphyrin transfers energy to O2 to generate which ROS?
    Back
    Singlet oxygen (a highly reactive non-radical ROS).
  68. Front
    In EPP , what is the cause of the patient's burning skin pain after light exposure?
    Back
    Direct oxidative damage to skin vessels/subcutaneous tissue by singlet oxygen (not ordinary inflammation).
  69. Front
    Why is molecular O2 itself a relatively POOR oxidizing agent in biological systems at room temperature?
    Back
    A spin-state restriction on its two unpaired electrons makes O2 react sluggishly unless activated (it must be reduced one electron at a time).
  70. Front
    How many unpaired electrons does ground-state molecular O2 have, and in what arrangement?
    Back
    Two unpaired electrons, in separate orbitals .
  71. Front
    Which two compounds in fava beans are hydrolyzed in the gut to species that generate H2O2 on oxidation (triggering favism )?
    Back
    Vicine and convicine .
  72. Front
    Catalase is notable for being one of the ______ enzymes known, processing how many substrate molecules per second?
    Back
    Fastest ; millions of H2O2 molecules per second.
  73. Front
    Protein oxidation modifies amino acid side chains to form which reactive functional group that impairs enzyme function?
    Back
    Carbonyl groups .
  74. Front
    Which three amino acid residues are especially susceptible to oxidative modification?
    Back
    Cysteine, methionine, and tryptophan .
  75. Front
    Moderate, orderly oxidative damage tends to kill a cell by ______, whereas overwhelming oxidative damage causes ______.
    Back
    Apoptosis; necrosis .
  76. Front
    In ischemia-reperfusion injury , why does restoring blood flow produce a burst of damage?
    Back
    Reperfusion floods the previously ischemic tissue with O2 and transition metals, generating a burst of hydroxyl radicals .
  77. Front
    Which fourth source of ROS arises from cytochrome P450 reactions in the endoplasmic reticulum of liver cells ?
    Back
    Drug detoxification (xenobiotic metabolism) by hepatic cytochrome P450 .
  78. Front
    Before prescribing primaquine for malaria prophylaxis, which patient status must be checked, and why?
    Back
    G6PD status — primaquine triggers hemolysis in G6PD-deficient patients who cannot regenerate NADPH / GSH .
  79. Front
    After GSH 's thiol donates an electron to a radical, what species forms, and how does it become GSSG ?
    Back
    A glutathionyl radical forms; two glutathionyl radicals combine to form the disulfide GSSG .
  80. Front
    Which plasma protein prevents free IRON from driving Fenton -type reactions by chelating it?
    Back
    Transferrin .
  81. Front
    Transferrin chelates iron to block Fenton chemistry; which plasma protein does the analogous job for COPPER ?
    Back
    Ceruloplasmin .
  82. Front
    Hypochlorous acid (HOCl) generated in the phagocyte oxidative burst is also the active ingredient of what common product?
    Back
    Bleach (it is a potent bactericidal agent).
  83. Front
    Besides G6PD , which second enzyme of the oxidative branch of the pentose phosphate pathway also generates NADPH ?
    Back
    6-phosphogluconate dehydrogenase .
  84. Front
    Glutathione (GSH) is the substrate for GPx , but it also acts as a direct non-enzymatic scavenger of which ROS?
    Back
    The hydroxyl radical (•OH) and other radicals — GSH belongs to both the enzymatic and non-enzymatic defenses.
  85. Front
    In chronic granulomatous disease , phagocytes can engulf but cannot kill which class of organisms?
    Back
    Catalase-positive organisms .

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