Free Radicals Flashcards
1
Q
what is a free radical
A
an atom or group of atoms (molecule) with one or more unpaired electrons
2
Q
what produces free radicals (3)
A
energy transfer (electrons), redox, enzymatic reactions
3
Q
what is homolytic cleavage (example)
A
A-B becomes A* + B*
4
Q
what is an example of energy transfer reaction that produced free radicals
A
H2O + hv –> HO* + H*
5
Q
what is an example reaction of an enzymatic process that produced free radicals
A
O2 + e- –> O2*-
6
Q
what are 3 examples of normal bodily enzymatic processes that produce free radicals (O2 + e- –> O2*-)
A
- phagocyte respiration burst
- mitochondrial respiration
- intracellular enzymes, metabolism
7
Q
what is the fenton reaction
A
Fe2+ + H2O2 –> Fe3+ + HO* + HO-
8
Q
which is the most reactive radical
A
OH radical
9
Q
what kind of diseases do free radicals cause
A
lots of them!!
10
Q
what are 4 things that can happen with macromolecule free radicals
A
mutation, catabolism, inactivation signalling
11
Q
what 2 things can happens once macromolecule free radicals cause signalling
A
toxicity or protection (apoptosis)
12
Q
what kind of species is H2O2
A
a pro-radical, just 1 step away from a free radical
13
Q
what are 2 main initiator free radicals
A
O2- and HO
14
Q
what is superoxide
A
O2*-
15
Q
What is hydroxyl radical
A
HO*
16
Q
what is a common reaction that makes the hydroxyl radical
A
H2O + hv –> HO- +H
17
Q
what is an example of a good free radical
A
NO*
18
Q
what is the difference with superoxide and normal diatomic oxygen
A
there is 1 more elctron
19
Q
how reactive is OH*
A
very
20
Q
what are reactive oxygen species
A
species that are derived from oxygen that are or have the ability to form free radicals
21
Q
what are reactive oxygen species compared to oxygen
A
they are more oxidizing that oxygen
22
Q
are all reactive oxygen species free radicals
A
no
23
Q
is hydrogen peroxide a free radical
A
no
24
Q
is singlet oxygen a free radical
A
no
25
what can cause the formation of singlet oxygen
light and photosensitizer
26
what is singlet oxygen diff with oxygen
two electrons fill one orbital and none in other (compared to one in ech in normal oxygen)
27
why is singlet oxygen a better oxidizer than oxygen
because it has has an empty orbital that it wants to fill with an electron
28
why is oxygen a diratical
because it has 2 unpaired electrons in its orbitals
29
why is oxygen unreactive
because the electrons have parallel spins
30
is singlet oxygen a ROS
yes
31
is singlet oxygen an electrophile or nucleophile
electrophile
32
is superoxide a reductant or oxidant
either
33
what is peroxynitrite
ONOO-
34
what is the reaction that forms peroxynitrite
O2*- + NO+ --> ONOO-
35
what is mitochondrial aconitase
an enzyme which is a target for ROS
36
why does aconitase react with superoxide
because it has iron that is solvent exposed which is electrophilic and reacts with superoxide (nucleophilic)
37
when can mitochondrial aconitase become a target for ROS attack
when the system is overwhelmed in trying to combat free radicals
38
what is the main reaction that happens in phagocytosis
NADPH + O2 --> NADP+ + O2*-
39
what happens after superoxide is produced in phagocytosis
it forms H2Oh then HOCl
40
what is the main enzyme responsible in phagocytosis
NADPH oxidase
41
what is consumed to make superoxide in phagocytosis
NADPH
42
what is the respiratory burst
oxidation of NADPH in order to generate superoxide
43
what activates the phagocytosis response
microorganisms and inflammatory mediators
44
what do microorganisms and inflammatory mediators activate
NADPH oxidase enzyme complex to crease phagocytosis
45
what is MPO and what does it do
enzyme that produces HOCl, called myeloperoxidase
46
how is MPO (myeloperoxidase) activated
superoxide is converted into H2O2 which activates MPO to generate HOCl
47
what enzymes helps produce HOCl
MPO
48
which complexes in the mitochondria make superoxide
1 and 3
49
how can some drugs effect ETC and cause ROS
they interfere with electron transport therefore electrons will leak and react with oxygen
50
how can drug metabolism cause ROS
from cytochrome P450 enzymes
51
how can cytochrome P450 enzymes lead to ROS production
an iron complex becomes unstable then it breaks apart and releases superoxide
52
when does xanthine oxidase work
activity occurs during oxidative stress/ proteolytic cleavage of the enzyme (ex: during ischemia reperfusion)
53
what does xanthine oxidase produce
mostly H2O2 and also superoxide
54
what does xanthine reductase do
lets NAD+ receive electrons
55
why are quinones bad
they are electron deficient and unstable
56
what can semiquinones do with the presence of oxygen
do redox cycling to make more and more superoxide radicals
57
Inhibition of mitochondrial respiration can lead to ROS, through inhibition of which complex
1 and 3
58
what happens in the redox cycle
semiquinone gets recycled with NADPH P450 reductase to create more and more superoxide anions (needs oxygen present)
59
what does superoxide often turn into
H2O2
60
with Fe++ present, what can H2O2 turn into
HO* hydroxyl radical
61
what happens with H2O2 and transition metals
fenton reaction
62
can H2O2 cross membranes
yes
63
is there free iron in the body and why
no because the fenton reaction is very toxic, so the body regulates iron very tight
64
what is the reaction rate with HO* like
diffisuion limited
65
are there specific OH* scavengers
no
66
what is the net reaction that makes the hydroxyl radical
O2*- + H2O2 --> O2 + OH- + OH*
67
what is the catalyst in the reaction : O2*- + H2O2 --> O2 + OH- + OH*
iron
68
what is the primary target for biological effects of ionizing radiation
DNA
69
what is the direct action of ionizing radiation damaging DNA
photon causes ionizing electron to be produced, electron travels and directly causes DNA damage
70
what is the indirect action of ionizing radiation damaging DNA
photon causes ionizing electron to be produced, electron interacts with water to produce radical ion species (OH*) which can damage DNA
71
is indirect or direct action of radiation damage to DNA more likely
indirect is more likely
72
which is the most susceptible base that reacts with DNA
guanine
73
what is a useful marker of oxidative DNA damage
8-hydroxydeoxyguanosine
74
what is the deal with 8-hydroxydeoxyguanosine
it is a useful marker of oxidative DNA damage
75
why is 8-hydroxydeoxyguanosine a useful marker of oxidative DNA damage
because guanine is the most likely base to be modified
76
what does lipid peroxidation do
cause physical damage to membranes
77
what kind of fats are highly susceptible to oxidation
polyunsaturated fatty acids
78
what happens once oxidized fatty acid products are made
they have biological activity
79
how can oxidized fatty acids be made
as products from both enzymatic and non enzymatic reactions
80
what are some examples of oxidized fatty acid products
hydroxyperoxides, isoprostanes, prostaglandins/leukotrienes, thromboxanes
81
why is damaging proteins more complicated compared to DNA
lots of differenta mino acids, so lots of different things can happen (sulferoxidation, crosslinkgs, carbonyls...)
82
is sulfer often oxidized or reduced and why
oxidized because it is nucelophilic
83
do proteins or DNA have more complex ways to be damaged
proteins
84
what can happen to protein or enzyme activity with oxidative modification
they usually lose activity, but sometimes they gain it
85
what happens to immunogenicity with damaged proteins and why
increased because the immune system recognizes it as foreign
86
what are 2 ways that glutathione conjugation can occur
either catalyzed by glutathione S-transferases or non-enzymatic
87
where is glutathione usually found (in the cell)
cytosol and endoplasmic reticulum
88
what is special about the structure of glutathione
it has an SH which is electron rich, it can act as a target for free radicals (acts as buffer to protect against free radicals)
89
what is the SH group called
thiol
90
what is the reaction that catalase does
2H2O --> O2 +2H2O
91
what kind of enzyme is catalase
heme enzyme
92
what is the role of catalase
gets rid of H2O2
93
what is the role of glutathione peroxidase
gets rid of H2O2 and lipid-OOH
94
what is a difference with glutathione and catalase
catalase only does H2O2, glutathione does that and more
95
is glutathione or catalase more versatile
glutathione
96
what are 2 main enzymes for peroxide detoxification
glutathione peroxidase and catalase
97
what is the general glutathione peroxidase reaction
2GSH + ROOH --> GSSG + ROH + H2O
98
what is lipid-OOH
hydroperoxide
99
what is hydroperoxide
Lipid-OOH
100
what does lipid-ooh and glutathione peroxidase generate (like with the lipid molecule)
lipid-OH (alcohol) which is non toxic
101
what is the cofactor for glutathione peroxidase
selenoenzyme
102
what are 2 superoxide detoxification antioxidant enzymes
Cu/Zn SOD and Mn SOD
103
where is Cu/Zn SOD
cytosol, also extracellular
104
where is Mn SOD
mitochondria (coded in nucleus)
105
what kind of SOD is found in the cytosol
Cu/Zn
106
what kind of SOD is found extracellularly
Cu/Zn
107
what kind of SOD is found in the mitochondria
Mn
108
what reaction does SOD catalyse
2O2*- +2H+ --> H2O2 + O2
109
what happens with Mn SOD knockout in mice
death in 10 days, damaged mitochondria and neurodegeneration
110
what happens with Cu/Zn SOD knockout in mice
increased O2 sensitivity, neurological damage and cancers
111
is Mn or Cu/Zn SOD worse to not have
Mn
112
what is the main form of Vitamin E
alpha-tocopherol
113
what is alpha-tocopherol
the main form of Vitamin E
114
what is the structure of the main form of alpha-tocopherol like
long fatty acid tail, lipid soluble
115
what is the major function of vitamin E
fat soluble chain breaking antioxidant
116
how is alpha-tocopherol an antioxidant (2)
peroxyl radical scavenger, protects polyunsaturated fats within membranes and lipoproteins
117
what is the major function of vitamin C
reducing agent in a number of different reactions, most important is hydroxylation of proline residues in collagen
118
is vitamin E fat or water soluble
fat
119
is vitamin C fat or water soluble
water
120
what does vit C deficiency cause and why
scurvy due to its role in PTM of collagen
121
where is a location with very high amounts of Vit C in the body
in neurons, but stored really well in the body at high concentrations
122
what does Vit C do to free radicals
scavenge them
123
what kind of substrates cause superoxide or H2O2 production by cytochdrome P450
weakly binding ones
124
does catalase require a cofactor
no
125
what functional group is found in both Vit E and C
hydroxyl group
126
what is the important structural feature of Vit E
the OH group
