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Biochem > Biochem Exam 1: Set 5 (Reactive Oxygen Species) > Flashcards

Biochem Exam 1: Set 5 (Reactive Oxygen Species) Flashcards

1
Q

What are some beneficial uses of free radicals?

A

synthesis of steroid hormones
kill bacteria in phagocytes
synthesis of some nucleotides
act as a paracrine hormone

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2
Q

What are some sources of uncontrolled (and harmful) free radicals?

A 
ischemic reperfusion injury
organ transplant
chemotherapy
aging
neurodegenerative diseases
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3
Q

What is ischemic reperfusion injury?

A

oxidative damage to tissue caused by free radicals when blood flow is restored

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4
Q

Define a radical and a free radical?

A

radical- a molecule with an unpaired electron

free radical- a radical that can diffuse about the cell

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5
Q

What ROS are present in the body?

A

superoxide
hydroxide radical
(hydrogen peroxide is not a radical but can easily generate them)

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6
Q

What compounds can catalyze the transfer of a single electron to oxygen making a superoxide radical?

A

Fe2+ and Cu+

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7
Q

Describe the Haber-Weiss reaction

A

superoxide + H2O2 + H+ –> O2 + H2O + hydroxide radical

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8
Q

Describe the Fenton reaction

A

H2O2 –> OH- + hydroxide radical (catalyzed by Fe2+ –> Fe3+)

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9
Q

Which classes of enzymes use oxygen directly?

A

oxidases- transfer electrons to oxygen forming water or hydrogen peroxide

oxygenases- incorporate one or both oxygen atoms into a substrate

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10
Q

What is gout?

A

Build up of uric acid in joints

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11
Q

How does xanthine oxidase contribute to myocardial reperfusion injury?

A

it oxidizes xanthine to uric acid and generates hydrogen peroxide.

Explanation: Ca2+ builds up in tissue during ischemia which induces the proteolysis of xanthine dehydrogenase to xanthine oxidase. Upon reperfusion xanthine oxidase activity increases generating H2O2.

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12
Q

Hydrogen peroxide from xanthine oxidase is converted to hydroxide radicals through what reaction?

A

Fenton reaction

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13
Q

What are the functions of cytochrome p450?

A

synthesize certain steroid hormones

degrades exogenic compounds (drugs, toxins, etc.)

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14
Q

What does C-p450 use as an electron source to add oxygen to substrates?

A

NADPH

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15
Q

How is nitric oxide produced?

A

produced by NO synthase using arginine, NADPH, and molecular oxygen to form citrulline

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16
Q

What is the function of NO in the body?

A

neurotransmitter and local hormone

causes vasodialation by binding to guanylyl cyclase

used in macrophages as a bactericide

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17
Q

What are the cofactors of NO synthase?

A

Fe-Heme, FAD, FMN, BH4

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18
Q

Where are superoxide anions produced?

A

produced by electron transport

can’t diffuse far before reacting

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19
Q

What ROS is produced during fat degradation?

A

organic peroxide radicals

20
Q

What is the most biologically potent radical and how is it produced?

A

hydroxyl radical

produced from hydrogen peroxide by the Fenton reaction in the presence of Fe2+ or Cu+

21
Q

What are the major ROS production sites in mitochondria?

A

Fe-S centers of complex 1
partially reduced ubiquinone
cyt-b in complex 3
cytochrome oxidase

22
Q

What percentage of oxygen used by the mitochondria will be converted to a ROS

A

1-2%

23
Q

What lipases are a major source of ROS?

A

arachidonic acid oxidation

24
Q

What oxidases are a major source of ROS/NROS?

A 
nitric oxide synthase
xanthine oxidase
NADPH oxidase
monoamine oxidase
p450 enzymes
25
Q

What chemical is used to measure the amount of reactive oxygen species in the body?

A

Malondialdenhyde (degradation product of organic peroxide radicals)

26
Q

Why are polyunsaturated fatty acids susceptible to reactions with free radicals?

A

conjugated double bonds stabilizes the fatty acid radical

27
Q

How can free radicals cause damage to DNA?

A

hydroxide radical can react with guanidine producing 8-hydroxyl-guanidine which is then converted to thymidine, leading to a mutation

28
Q

How can free radicals effect proteins?

A

free radicals can attack cysteine and cause crosslinking

nitrated tyrosine may be linked to inflammatory disease

29
Q

What oxidative enzymes are used in macrophages to phagocytize bacteria?

A

iNOS
SOD
myeloperoxidase
(NADPH oxidase is used extracellularly)

30
Q

What factors contribute to an increase in reactive oxygen species?

A

inflammation, radiation, aging, smog, chemicals, drugs, reperfusion, high pO2

31
Q

What cellular defense mechanisms are used to combat ROS’s?

A

compartmentalization
free radical scavengers (vitamin C and E)
DNA repair mechanisms
protective enzymes

32
Q

How does glutathione help prevent oxidative damage?

A

converted from a reduced to an oxidized form by glutathione peroxidase and converts hydrogen peroxide to water

33
Q

Where is glutathione peroxidase found and what cofactor is required in some isoforms?

A

found in mitochondria and cytosol

some require selenium

34
Q

Besides glutathione peroxidase, what other enzymes are involved in the glutathione oxidative defense mechanism?

A

glutathione reductase- converts oxidized glutathione back to reduced form by converting NADPH to NADP+

glucose-6-phosphate dehydrogenase- maintains NADPH levels so glutathione reductase can keep glutathione reduced (especially important in red blood cells)

35
Q

What 2 enzymes function to defend the cell from oxidative damage?

A

superoxide dismutase

catalase

36
Q

Where is superoxide dismutase found and what activates it?

A

different isozymes in cytosol, mitochondria, and extracellular matrix

induced by oxidative stress

37
Q

What reaction is catalyzed by superoxide dismutase?

A

2 superoxide radicals + 2 H+ –> H2O2 + O2

38
Q

What reaction is catalyzed by catalase?

A

2 H2O2 –> 2 H2O

39
Q

Where is catalase found?

A

in peroxisomes and cytoplasm of phagocytes

40
Q

What factor limits the kinetics of catalase?

A

limited by the diffusion rate of peroxide in water (very fast enzyme)

41
Q

What are the major biological antioxidants?

A

vitamin E (tocopherol)
vitamin C (ascorbate)
vitamin A
flavonoids

42
Q

What tissue is protected from oxidative damage by vitamin E?

A

vitamin E is lipophilic, protects against lipid membrane peroxidation

43
Q

What Vitamin A precursors may also function beneficially as antioxidants?

A

beta-carotene

44
Q

What is the major source of flavonoids?

A

food (primarily vegetables, wine, and beer)

45
Q

Describe ischemic postconditioning

A

interruption of reperfusion with short cycles of ischemia

46
Q

What event during reperfusion causes the opening of the mitochondrial transition pore?

A

abrupt increase in Ca2+

Biochem (6 decks)

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