ROS Flashcards

1
Q

Formation of superoxide anion radical related to the ETC or cytochromes

A

If the one e- reduced form of CoQ (CoQH*) accidentally comes into contact with dissolved O2 it can transfer an e- to it, thereby generating the superoxide.

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2
Q

Ionising Radiation generation of Hydroxyl radical

A

IR- generates highly reactive free radicals via H2O

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3
Q

Haber-Weiss rxn generation of Hydroxyl radical

A

Hydrogen peroxide + Superoxide -> Hydroxyl radical

  • non-enzymatic rxn
  • transition metal e.g. Fe2+ or Cu2+ can catalyze rxn
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4
Q

Fenton rxn generation of Hydroxyl radical

A

Hydrogen peroxide -> Hydroxyl radical + hydroxyl ion

  • Requre Fe2+
  • As free metals can initiate this rxn, therefore usually protein bound and found in trace amounts only
  • Crush injuries tend to release Fe2+ from storage sites & generate high levels of free radical injury
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5
Q

ROS damage on protein

A
  • Exposure of proteins to ROS causes gross structural mods -> spontaneous fragmentation or increased proteolysis (Pro, His, Arg, Cys, Met particularly susceptible)
  • Oxidised aa can also form abnormal cross-links with other residues. CYS cross-linking can prevent the degradation of aggregated proteins.
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6
Q

ROS damage on DNA

A

2’-deoxyguanosine -> oxidation -> 8-hydroxy-2’-deoxyguanosine (biomarker for DNA oxidation; cancer) -> results in mis-pairing of G with A

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7
Q

ROS damange on lipids

A

Lipid peroxidation also produces toxic aldehydes including malondialdehyde which can damage DNA by forming bulky adducts with G, A, and C.

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8
Q

SOD-1 scavening of ROS

A
  • catalyzes dismutation (reversal) of superoxide back to O2
  • 3 isoforms:
    o Cytosolic
    o Mitochondrial
    o Extracell: increased by chemicals or conditions that increase the production of superoxide
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9
Q

Catalase scavening of ROS

A
  • Found principally in peroxisomes & to a lesser extent in cytosol & microsomal fractions of cell extracts
  • H202 once formed must be reduced to H20 to prevent it from forming the hydroxyl radical in the Fenton or Haber-Weiss rxn.
  • highest activity found in liver & kidney due to high numbers of peroxisomes
  • in cells of immune system, catalase serves to protect the cell against its own respiratory burst
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10
Q

Glutathione scavenging of ROS

A
  • Glutathione Reductase:
  • Glutathione Peroxidase:
    • requires Selenium
    • detox peroxide into water
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11
Q

ROS formation as an immunological response

A
  • Major source of deliberate production of ROS & RNOS by neutrophils in order to kill invading microorganisms.
  • NOS isoform II: inducible; present in many of the immune systems cells (with similar lineage) such as macrophages & brain astroglia
    • Only expressed during infection
    • Uses Arginine as reactant to produce NO + Citrulline
    • NO* induces NADPH Oxidase activity to generate other cytocidal ROS & RNOS
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