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FoundSci Unit 6 > Oxidative Stress and Antioxidants > Flashcards

Oxidative Stress and Antioxidants Flashcards

1
Q

What are the types of reactive oxygen species (ROS)?

A

Superoxide radical - not very reactive, second messenger

Hydrogen peroxide - reactive, second messenger

Hydroxyl Radical - most reactive and destroying ROS

Singlet oxygen - exists only at high temperature or in response to radiation

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2
Q

What are reactive oxygen species?

A

Partially reduced, reactive forms of oxygen

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3
Q

What is the path of oxygen to other ROS?

A

Oxygen

Superoxide (O2-)

Hydrogen peroxide (H2O2)

Hydroxyl anion (OH-) and Hydroxyl radical (OH-)

H2O

SEPARATE PATH
Oxygen to Singlet Oxygen via energy transfer

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4
Q

What is the electron transport chain a source of?

A

Superoxide radical

Main source of leaking electrons is the semiquinone (UQH)

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5
Q

What is the function of cytochrome P450 oxidase?

A

Hydroxylation of variety of substrates

Active site is heme - iron center

NADPH is required

2 atoms of O2 are used

One O atom hydroxylates S and second O atom forms water

If second transfer fails, superoxide radical is formed

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5
Q

What is the location of cytochrome P450 oxidase?

A

Membranes of ER

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6
Q

What is MEOS and what is it a source of?

A

Microsomal Ethanol Oxidation System

Requires CYP450E1 enzyme and is alternate pathway of ethanol metabolism in liver

Active during chronic alcohol consumption

Source of hydrogen peroxide and hydroxyethyl radical (mutagenic)

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7
Q

What is the MEOS equation using CYP450E1 enzyme?

A

Ethanol + 2O2 + NADPH

to

Acetaldehyde + 2 H2O2 + NADP + Hydroxyethyl radical

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8
Q

What does hydroxyethyl radical lead to?

A

Liver cancer

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9
Q

What does hydrogen peroxide from MEOS lead to?

A

Lipid peroxidation of liver cell membranes

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10
Q

What is the NADPH-Dependent Oxidase System?

A

Found on membranes of phagocytic cells

Activated in response to bacterial infection and inflammation

Robust response to bacterial infection can lead to Respiratory burst which leads to formation of superoxide radical, hydrogen peroxide, and hydroxyl radicals

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11
Q

What is xanthine oxidase and what ROS does it produce?

A

Catalyzes oxidation of hypoxanthine and xanthine to uric acid

Hypoxanthine is from inosine which is from the purine degradation pathway

Source of hydrogen peroxide

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12
Q

What is the Fenton Reaction?

A

Free iron (Fe2+) and copper (Cu+) donate an electron to hydrogen peroxide

Source of Hydroxyl Radicals

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13
Q

What is superoxide dismutase?

A

Coverts superoxide radical into hydrogen peroxide

2O2- + 2H+ -> H2O2 + O2

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14
Q

What are antioxidant enzymes?

A

Catalase (peroxisomes)

Glutathione peroxidase

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15
Q

What does catalase in peroxisomes do?

A

Antioxidant enzyme

Detoxifies hydrogen peroxide

2H2O2 -> 2H2O + O2

16
Q

What does glutathione peroxidase do?

A

Antioxidant enzyme

Detoxifies hydrogen peroxide and lipid peroxides

H2O2 + 2GSH -> 2H2O + GSSG

17
Q

What are antioxidant vitamins?

A

Vitamin C (ascorbic acid)

Vitamin E (alpha-tocopherol)

Vitamin A retinoid (animals) and Beta-carotene (plants)

18
Q

How does vitamin C act as a antioxidant and what is it?

A

Water soluble vitamin

Reduces superoxide radicals, organic radicals, and lipid peroxides

Becomes radical itself (GSH regenerates Vit C) and recycles vitamin E

19
Q

How does vitamin E acts as a antioxidant and what is it?

A

Lipid soluble vitamin

Detoxifies free radicals and terminates lipid peroxidation in membranes

Plentiful vegetable oils

20
Q

How does vitamin A retinoid and Beta-carotene acts as an antioxidant and what is it?

A

Lipid soluble vitamin

Conjugated double bonds in vitamin A are capable quenching the vibration energy of singlet oxygen

21
Q

What is glutathione (GSH)?

A

Water soluble antioxidant

Tripeptide (glutamate, cysteine, and glycine)

Cysteine thiol group donates electrons to ROS

Oxidized form is GSSG

22
Q

How does glutathione function as an antioxidant?

A

GSH serves as cofactor of glutathione peroxidase

Leads to GSH oxidation to GSSG

GSSG reduced back to GSH by glutathione reductase

Hydrogen peroxide is converted to water

Pentose phosphate pathway provides NADPH to recover GSH

23
Q

What are polyphenols (flavenoids)?

A

Water soluble antioxidants from plant extracts

24
Q

What is uric acid?

A

Major serum antioxidant

25
Q

What is bilirubin as an antioxidant?

A

Lipid soluble, unconjugated bilirubin donates an electron to radicals

Oxidation coverts bilirubin back to biliverdin

26
Q

How are antioxidants regenerated?

A

Radical abstracts electron from PUFA (polyunsaturated fatty acid)

PUFA radical is quenched by vitamin E

Vitamin E is regenerated by vitamin C

Vitamin C is regenerate by GSH

GSH is recovered by NADPH

NADPH comes from pentose phosphate pathway

27
Q

What is oxidative stress?

A

Irreversible damage caused by attack of ROS upon protein, lipids, and DNA of cells

Results from imbalance between ROS (pro-oxidants) and antioxidants

28
Q

What makes red blood cells vulnerable to oxidative stress?

A

High oxygen saturation

29
Q

What are the major defense mechanism of red blood cells?

A

Glutathione peroxidase

Glutathione (GSH)

Pentose Phosphate Pathway - helps to destroy hydrogen and organic peroxides

Methemoglobin reductase - recovers hemoglobin and replaces electrons to the iron in the heme of methemoglobin

30
Q

What is lipid peroxidation?

A

Hydroxyl radicals (OH) cause peroxidation of PUFAs in the membranes

31
Q

What are the steps in lipid peroxidation?

A

OH radical (hydroxyl radicals) abstracts an electron from a PUFA producing a lipid radical

Lipid radicals react with oxygen to form lipid peroxyl radicals

Lipid peroxyl radicals are unstable and either abstract electron from other PUFA double bonds (propagation or chain reaction) or form lipid peroxides that break down into malondialdehyde (mutagenic)

32
Q

What are major antioxidants for lipid peroxidation?

A

Vitamin E

Glutathione peroxidase (GPx)

33
Q

What ROS damages DNA?

A

Hydroxyl radical damages DNA

Produces DNA double strand breaks - cuts chromosome in two

Can bind guanine bases forming 8-oxoguanine that interferes with replication and transcription

34
Q

How do ROS cause protein damage?

A

ROS abstract electrons from thiol groups

This leads to formation of incorrect disulfide bonds

Proteins become inactive and are degraded

35
Q

How do is oxidative stress prevented?

A

ROS and antioxidants must be in equilibrium

Not all ROS are bad - redox signaling and thyroid hormone synthesis requires H2O2

FoundSci Unit 6 (14 decks)

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