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MCP Unit 8 > Reactive Oxygen Species > Flashcards

Reactive Oxygen Species Flashcards

1
Q

Primary ROS

A
  • Superoxide (*O2-)
  • Free radical with moderate reactivity
  • Formed from one electron reduction of oxygen
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2
Q

Secondary ROS (H2O2)

A
  • Hydrogen peroxide (H2O2)
  • Oxidant, not a free radical
  • Low reactivity but can generate the hydroxyl radical
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3
Q

Secondary ROS (*OH-)

A
  • Hydroxyl radical
  • Unpaired electron is much more unstable than superoxide, highest reactivity
  • Electron stealer to form water
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4
Q

Generation of superoxide

A
  • Occurs in mitochondria as a byproduct of ATP synthesis
  • Premature leakage of oxygen during ETC
  • Complex III: one electron transfer to produce superoxide
  • Complex I can also generate superoxide
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5
Q

What can lead to increased production of superoxide?

A
  • High membrane potential: slower electron transfer, greater reduction level of electron carriers and electron leak
  • High NADH/NAD ratio: overreduction of ETC
  • Electron transport chain damage
  • Xenobiotics: may block ETC thus increasing reduction
  • Electron backflow in complex I: ischemia, reperfusion injury leads to overreduction
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6
Q

NADPH oxidases

A
  • Superoxide production in cells such as phagocytes: kill invading pathogens
  • NADPH + 2O2 –> NADP+ +2*O2- + H+
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7
Q

Xanthine oxidase

A
  • In liver and endothelial cells
  • Catalyzes purine metabolism
  • Xanthine + O2 –> Uric acid + *O2-(+H2O2)
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8
Q

Monoamine oxidase

A
  • Type b catalyzes dopamine catabolism in neuronal cells

- Dopamine –> DOPAC + NH3 + H2O2

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9
Q

Fenton reaction

A
  • Conversion of H2O2 to hydroxyl radical
  • Transfers an electron from free metal ions (ex: Fe2+)
  • Presence of iron is catalytic: overaccumulation can lead to oxidative stress
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10
Q

Ionizing radiation

A
  • Can produce hydroxyl radical
  • Induces homolytic fission of O-O bond in H2O2.
  • Kills tumor cells
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11
Q

Primary reactive nitrogen/oxygen species

A
  • Nitric oxide

- Can react with superoxide to form peroxynitrite (ONOO-) which is very reactive and can also form hydroxyl radical

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12
Q

Generation of NO

A

-Nitric oxide synthase: metabolizes arginine to citrulline with formation of NO.

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13
Q

Five major reactive oxygen species

A
  • Superoxide
  • Hydrogen peroxide
  • Hydroxyl radical
  • Nitric oxide
  • Peroxynitrite
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14
Q

Places where oxidative damage may occur

A
  • DNA: favored for OH caused by fenton reaction, nucleic acids bind iron well
  • Protein
  • Lipid
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15
Q

Indicator for extent of DNA damage in the cell

A
  • 8 hydroxyldeoxyguanosine resulting from guanosine oxidation
  • Can mispair with deoxyadenosine and lead to G to T transversion
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16
Q

Lipid peroxidation

A
  • OH is active in mediating lipid oxidation
  • PUFA highly susceptible: oxygens close to double bonds are highly reactive
  • Lipid peroxidation can initiate a free radical chain reaction in the membrane to produce lipid peroxide which causes membrane damage
  • Highly reactive aldehydes also accumulate
17
Q

Protein carbonylation

A
  • Hydroxyl radicals can directly oxidize amino acid side chains and cause protein damage
  • Can also add reactive carbonyl function groups on proteins: most common are reactive aldehydes generated from lipid peroxidation
  • Can cause conformational change, loss of activity, and/or protein turnover
18
Q

H2O2 and thiols

A

-H2O2 can oxidize some protein cysteinyl residues to form disulfide cross links with other cysteines

19
Q

Superoxide dismutase

A
  • Converts two molecules or superoxide into one molecule of O2 and one H2O2
  • Sod1: cytosolic, contain Cu and Zn
  • Sod2: mitochondrial, contains Mn
20
Q

Mutation in Sod1

A
  • Amyotrophic lateral sclerosis

- Sod1 is misfolded and becomes cytotoxic

21
Q

Glutathione peroxidase

A
  • Converts H2O2 to water while consuming two molecules of reduced glutathione
  • Contains micronutrient selenium
22
Q

Glutathione reductase

A
  • Regenerates reduced glutathione

- NADPH dependent: depends on pentose phosphate pathway and G6PDH

23
Q

Peroxiredoxin pathway

A
  • Uses small sulfhydryl containing proetin peroxidoxin to detoxify H2O2
  • Forms water and oxidized peroxiredoxin which is then reduced by thioredoxin
  • Thioredoxin reduced by thioredoxin reductase
24
Q

Catalase

A
  • Heme containing enzyme
  • Catalyzes decomposition of H2O2 to water and oxygen
  • Usually located in peroxisome
25
Q

Mechanism of antioxidants

A
  • Scavenge free radicals

- Protecting proteins against sulfhydyl oxidation

26
Q

Coenzyme Q10 (ubiquinone)

A
  • In vivo synthesized antioxidant

- Scavenges RO2 free radicals and inhibits lipid peroxidation

27
Q

Glutathione

A
  • In vivo synthesized antioxidant
  • Keeps sulfhydryls of proteins reduced
  • Donates electron to free radicals

MCP Unit 8 (8 decks)

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