lecture 10 Flashcards

(39 cards)

1
Q

what is oxidation

A

gain in oxygen, loss of hydrogen, loss of electrons

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2
Q

what is reduction

A

loss of oxygen, gain of hydrogen, gain of electrons

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3
Q

what is an oxidant

A

oxidizes another chemical by taking electrons, hydrogen, or by adding oxygen

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4
Q

what is a reductant

A

reduces another chemical by supplying electrons, hydrogen, or by removing oxygen

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5
Q

what are free radicals

A

free radicals attack and snatch energy from other cells to satisfy themselves

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6
Q

what are the most important pro-oxidants

A

ROS and RNS

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7
Q

what are some examples of free radicals

A

they have one or more unpaired electrons, so carbon center, nitrogen centered, oxygen centered, and sulfur centered

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8
Q

how are non radicals characterized?

A

has strong oxidizing potential or help to form strong oxidants

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9
Q

how long can some pro oxidants live for?

A
  • hydrogen peroxide can live for minutes
  • nitric oxide can live for seconds
  • singlet oxygen can live for microseconds
  • hydroxyl radical can live for nanoseconds
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10
Q

what are some endogenous sources of ROS

A
  • endoplasmic reticulum
  • cytoplasm
  • mitochondria
  • lysosomes
  • peroxisomes
  • plasma membrane
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11
Q

what does 90% of ROS from a cell come from?

A

the mitochondria, ETC contains several redox centers that may leak e- to oxygen

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12
Q

what is the result of oxidative damage to lipids from mitochondrial oxidative stress?

A

membrane peroxidation and decreased membrane fluidity

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13
Q

what is the result of oxidative damage to DNA from mitochondrial oxidative stress?

A

mutations and deletions

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14
Q

what is the result of oxidative damage to proteins as result of mitochondrial oxidative stress

A

oxidation of sulfhydryl groups, reactions with aldehydes and protein aggregation

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15
Q

where is NADPH oxidase mainly present in?

A

mainly in neutrophils but still present in many other cell types

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16
Q

why does NADPH oxidase make ROS on purpose?

A

because absence of ROS will result in chronic granulomatous disease

17
Q

how does lysosomes generate ROS and RNS

A

through myeloperoxidase

18
Q

how does peroxysomes generate ROS and RNS

A

through enzymes

19
Q

what does lipid peroxidation lead to?

A
  • structural changes in membranes
  • adducts/crosslinkes with non lipids
  • direct toxicity of lipid peroxidation products
  • dna damage and mutagenesis
20
Q

what are the structural changes in membranes that come from lipid peroxidation

A
  • alter fluidity and channels
  • alter membrane bound signaling proteins
  • increases ion permeability
  • disruptions in membrane dependent signaling
21
Q

what are the consequences of protein oxidation?

A
  • oxidation of catalytic sites on enzymes
  • formation of mixed sulfide bonds
  • increased susceptibility to proteolysis
22
Q

what are the consequences of DNA oxidation?

A
  • dna adducts/AP sites/strand breaks results in mutations or initiations of cancer
  • overstimulation of dna repair
23
Q

what does oxidation of catalytic sites on enzymes result in?

A

causes loss of function/abnormal function

24
Q

what exactly happens in overstimulation of dna repair?

A
  • can deplete energy reserves of cell (PARP)
  • induction of error prone polymerases
  • activation of checkpoint related signaling pathways
25
what are the exogenous sources of free radicals?
- irradiation - chemicals that react to form peroxides - chemicals that promote superoxide formation - chemicals that are metabolized to radicals - iron
26
what are the ways oxidants can act to modify signal transduction?
- heme oxidation - oxidation of iron sulfer centers - changes in thiol/disulfide redox state - change in conformation - oxidative modification of proteins - oxidative modification of dna - oxidative modification of lipids
27
what does high does of oxidative stress and cell damage do?
-directly damages and kills cells
28
what does low doses/chronic overproduction of oxidants do?
- activation of cellular pathways - stimulation of cell proliferation - damage to cellular proteins, DNA and lipids
29
what are defensive mechanisms against pro-oxidants?
1. prevention of prooxidant formation 2. interception of proxoxidants 3. breaking the chain of radical reactions 4. repair of damage caused by prooxidants
30
what is the free radical theory of aging?
steady state accumulation of oxidative damage that increases during aging, progressive loss in efficiency of cellular processes
31
what are the lessons learned from MnSod knockdown mice?
- mitochondrial antioxidant enzyme peroxide is less dangerous than superoxide - homozygous mutant is lethal - 50% decrease in MnSod activity in all tissues studied - no compensation by other major antioxidant enzymes
32
what organelle's function is lost in SOD2 (+/-) mice
mitochondria: - leads to oxidative damage to specific mito proteins - altered mitochondrial function leads to decreased activities of ETC
33
MnSOD hetero knockout mice have same lifespan but have more what?
cancers
34
what happens when catalase levels decline with age?
hydrogen peroxide cannot be broken down, allows hair to be bleached from the inside out
35
what is the overall importance of mitochondrial function in aging prevention?
- 3-5 fold increase in point mutations and deletion in mtDNA - normal appearance until about 6 months, weight loss, kyphosis, decreased fat, osteoporosis - decreased ETC C activity and ATP production
36
what kind of dna is more sensitive to oxidative damage than nuclear dna?
mtdna
37
what chronic diseases are linked to ROS action
- inflammation - atherosclerosis - ischemia/reperfusion injury - injury
38
tissues that turn over more slowly (skeletal and heart muscle) have more what than more rapidly dividing tissues (liver)?
more mtdna deletion
39
deletions increase with age in what two organs?
heart muscle and brain