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Block 1 > W3: Sublethal Injury and Adaptation > Flashcards

W3: Sublethal Injury and Adaptation Flashcards

1
Q

What is the most damaging free radical?

A

Hydroxyl radical: OH

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2
Q

What are examples of ROS (reactive oxygen species)

A

Free radicals: hydroxyl radical

Other reactive species: hydrogen peroxide

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3
Q

What is the primary location of ROS generation?

A

Mitochondria

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4
Q

Where is the major continuous source of ROS?

A

Mitochondria

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5
Q

Describe the Fenton reaction. Where does it occur?

A

Iron turns hydrogen peroxide into hydroxyl radical; mitochondria

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6
Q

The longer the ROS lives, the more/less damage there is.

A

Less (longer lived means less reactive; inverse relationship)

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7
Q

Cysteine residues are especially susceptible to ROS because of theirf __ group.

A

SH (S-S cross linking)

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8
Q

What are amino acids susceptible to adduct formation (addition product) from ROS?

A

Lysine, cysteine, tyrosine

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9
Q

What are 4 effects of ROS on protein?

A

S-S cross-linking,
adduct formation (addition product),
protein unfolding,
protein scission (splitting apart)

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10
Q

What are 6 effects of ROS on lipids?

A

ROS lipid propagation of ROS
lipid cross-linking
lipid scission
membrane fluidity

FAO
4-HNE formation (carbonylation)

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11
Q

PUFA –ROS–> PUFA-OOH —> 4-HNE –> attachment of protein (___)

A

Carbonylation

ROS effect on lipid

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12
Q

When PUFA is oxidized by ROS, ___ carbonylation occurs, attaching ____ to the FA.

A

4-HNE, proteins

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13
Q

_____ is usually the starting ROS. But much of cell damage is result of ____ diffusing throughout and being converted to the highly reactive ____ radical.

A

Superoxide, H2O2, hydroxyl

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14
Q

Lipid peroxidation byproduct ___ causes ___, a covalent modification of lipid by adding protein.

A

4-HNE, carbonylation

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15
Q

__ % of acetaminophen usually gets excreted by ___ but __% yield superoxide and reactive/toxic intermediate (NAPQI).

A

95, hepatocyte, 5

common clinically

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16
Q

What vitamins function as free radical quenchers?

A

E - reduces (redox) lipid peroxide radicals***

C - reduce (redox) vitamin E and quenches free radicals

A - may quench singlet oxygen

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17
Q

A reduced _____ is a major cellular anti-oxidant that quenches oxygen free radicals.

A

Glutathione (GSH)

Reduced glutathione (GSH) - by reductase (replenish GSH)
Oxidized glutathione (GSSG) - by peroxidase (convert H2O2 to H2O)
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18
Q

__to __ ratio is an indicator of cellular oxidative stress (redox state). Increase in ___ indicates to oxidative stress.

A

GSSG/GSH, GSSG

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19
Q

___ can treat acetaminophen toxicity because it is converted to ___ in ___, reducing the toxic intermediate (NAPQI).

A

NAC (N-acetylcysteine), glutathione, hepatocytes

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20
Q

Acetaminophen detoxification: ___ –> GSH in the liver, which creates non-toxic NAPQI conjugate.

A

NAC (N-acetylcysteine)

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21
Q

Vit E/C replenishes vit E/C.

A

C (water) replenishes E (fat).

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22
Q

Fava beans incur no cell injury to normal cells but can damage ___ when there is not enough enzyme ___ to replenish ___.

A

RBC, G6P-DH, NADPH

this is because G6P-DH is the only enzyme producing NADPH in RBC

23
Q

Glutathione __ replenishes GSH with help of NADPH, which is dependent on enzyme___ in the RBC.

A

Reductase, G6P-DH

24
Q

In RBC, ___ is the only enzyme that produces NADPH.

A

G6P-DH

25
Q

In G6P-DH deficient red cell, fava bean can lead to acute hemolytic anemia due to build up of ___.

A

Hydrogen peroxide (H2O2)

26
Q

In UPR (unfolded protein response), ubiquination of misfolded protein leads to degradation inside ___.

A

Proteasome (ubiquitin-proteasome pathway)

27
Q

Autophagy is activated when two instances occur:

A

Damaged organelle recognition

Nutrient deprivation states

28
Q

Inside the cell, organelle __ detects misfolded proteins through three sensory molecules that communicate with the nucleus to activate genes.

A

ER (sensory molecules: PERK, IRE1, ATF6)

29
Q

UPR (unfolded protein response): Detection of misfolded proteins by ER promotes two actions:

A

1) Activate trxn of genes to handle the damage

2) Deactivate cell division

30
Q

DNA damage response: Proteins that sense DNA damage promote recruitment of other proteins to induce 2 cellular responses:

A

1) Cell cycle arrest (inhibition of replication)

2) Apoptosis (if severe)

31
Q

Cell stress leads to apoptosis, it will enter intrinsic/extrinsic pathway of apoptosis.

A

Intrinsic (mitochondrial)

32
Q

Intrinsic pathway of apoptosis involves release of ___ from mitochondria, leading to activation of ___ cascade. It is also associated with __ family.

A

Cytochrome c, caspase, Bcl-2

33
Q

What is Nrf2 and what does it do?

A

Nuclear factor E2-related factor 2;

a redox sensitive TF that increase trxn of protective genes under cellular stress

34
Q

What is Keap and it’s function?

A

Sensory protein that ubiquinates (degrades) Nrf2.

35
Q

Default: when ROS is low, Nrf2 is activated/degraded.

A

Degraded (by proteasome)

36
Q

Keap is inactivated when ROS level is low/high, leading to activation/degradation of Nrf2.

A

High, activation

37
Q

Keap is an enzyme that adds/detaches ubiquitin to Nrf2, leading to Nrf2 activation/degradation.

A

Adds (ubiquitin ligase), degradation

38
Q

Why are antioxidant supplements not shown to work?

A

May be because ROS lead to redox signaling of adaptive and protective activities. Although antioxidants may inhibit damage caused by ROS, it may also block beneficial signaling pathway activated by ROS.

39
Q

Major free radical produced by cells is O2/H2O2/OH, which is relatively unreactive with DNA, lipid, and protein.

A

O2 - superoxide radical

40
Q

O2/H2O2 diffuses well across the membrane and can introduce radicals from cytoplasm to nucleus

A

H2O2

41
Q

ROS ___ is made during FAO by peroxisomes.

A

H2O2

42
Q

OH radical is formed when ___ reacts with ___.

A

Iron (Fe), hydrogen peroxide (H2O2)

Fenton Reaction

43
Q

Strength: superoxide radical < hydrogen peroxide < hydroxyl radical. Write their chemical equation.

A

Rad O2, H2O2, rad OH

44
Q

Two reactive nitrogen species (RNS) are:

A

Peroxynitrite

Nitrogen dioxide radical

45
Q

Three important metabolites for antioxidant defense mechanisms include:

A

Glutathione, tocopherol (vit E), ascorbic acid (vit C)

46
Q

Name the 5 most important enzymes for antioxidant defense mechanism (hint: 3 categories):

A

SOD, catalase (hydrogen peroxide)

glutathione peroxidase*, glutathione reductase (glutathione)

heme oxygenase (free iron)

47
Q

Glutathione ___ replenishes GSH, and Glutathione ___ makes ___ and H2O from H2O2.

A

Reductase, peroxidase, GSSG

48
Q

___ carbonylation covalently modifies proteins which can affect major biochemical processes, including gene expression, protein secretion and function, and signal transduction.

A

4-HNE (4-hydroxyl-nonenol)

49
Q

4-HNE carbonylation can occur with the following residues (aa):

A

His, Cys, Lys

50
Q

ROS leads to oxidative modification of DNA via (2)

A

base pair mismatching

DNA strand breakage

51
Q

__ of FA allow propagation of ROS in membranes (which changes the composition)

A

polyunsaturated double bonds

52
Q

What is the treatment for acetaminophen toxicity?

How?

A

NAC (N-acetylcysteine)

NAC is converted to glutathione in the liver!

53
Q

the symptom of acute hemolytic anemia due to fava bean

A

enlarged spleen due to increased hemolytic lysis

54
Q

ROS is directly detected by

A

Nrf2

Block 1 (26 decks)

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