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Fall-Foundational Sciences Year 1 > Oxidative Stress and Antioxidants > Flashcards

Oxidative Stress and Antioxidants Flashcards

1
Q

free radical

A

atom/molecule/ion with an unpaired valence electron

aka ROS

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2
Q

superoxide

A

oxygen gains an electron

not very reactive, can be used as second messanger

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3
Q

hydrogen peroxide

A

H202
reactive, second messangers

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4
Q

hydroxyl radical

A

most reactive and dangerous

3 electrons added to oxygen

produced by H2O2 in Fenton rxn w/ Fe2+ and Cu+

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5
Q

sources of ROS

A
  1. Mitochondria ETC
  2. cytochrome P450 oxidase
  3. MEOS and Alcohol induced liver damage
  4. NADPH dependent oxidase system (phagocytic cells)
  5. xanthine oxidase
  6. iron and copper ions
  7. radiation
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6
Q

mitochondrial ETC

A

superoxide radicals released from UQH (b/t complex I and III)

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7
Q

cytochrome p450 oxidase

normal mechanism

A

membrane of ER @ liver
heme-iron center of active site

step 1: one electron transferred from NADPH and one oxygen hydroxylates the substrate
step 2: second electron transferred from NADPH, another oxygen makes water

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8
Q

MEOS and alcohol induced liver damage

A

gets activated w/ chronic alc consumption

CYP450E1 converts ethanol to acetaldehyde via redox

can potentially produce large amounts of hydrogen peroxide and hydroxyethyl radical

hydroxy radical is mutagenic = DNA mutations = liver cancer

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9
Q

skin lesions in PCT

responsible

A

uroporphyrins NOT MEOS

light gets absorbed then energy is transferred to oxygen = ROS

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10
Q

NADPH-dependent oxidase

A

in phagocytic cells

gets activated by inflamation from bacterial infections

produce superoxide radicals via respiratory burst > converted to hydroxyl radicals = destroy bacteria

good thing

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11
Q

chronic granulomatosis disease

A

deficiency in NADPH oxidase = respiratory burst compromised

inc susceptibility to bacterial and fungal infections

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12
Q

xanthine oxidase

A

part of purine degradation = uric acid
2 molecules hydrogen peroxide made

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13
Q

iron and copper ions

A

both are redox reactive so participate in one electron transfers = hydroxyl radicals

since so damaging kept in low concentrations in blood by being bound to proteins or tetrapyrroles (heme or cytochrome)

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14
Q

fenton reaction

A

iron + superoxide radical + hydrogen peroxide = hyroxyl radicals

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15
Q

hereditary hemochromatosis

A

iron storage disease from mutations in HFE gene

acc iron> deposited in cells = excess iron> oxidative stress = destroy liver, pancreas, heart

pt will have bronze skin

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16
Q

iron overload

other causes

A

thalassemia and sickle cell (bc hemolysis so hemoglobin and heme more prone to ROS when released from RBC)

frequent blood transfusions

17
Q

radiation

A

direct: directly destroy DNA, proteins, and lipids

indirect: water molecule split into hydrogen and hydroxyl radicals
-radicals> double strand breaks in DNA = mutations and destruction esp if actively dividing

indirect used for tumor therapy

18
Q

antioxidant categories

A

antioxidative enzymes
vitamins
metabolic antioxidants

19
Q

antioxidative enzymes

A
  1. superoxide dismutase
  2. catalase
  3. glutathione peroxidase
20
Q

superoxide dismutase

SOD

A

converts superoxide radical > hydrogen peroxide

21
Q

catalase

A

detoxifies hydrogen peroxide > water

heme containing enzyme in peroxisomes

22
Q

glutathione peroxidase

A

detox hydrogen peroxide and lipid peroxidases

uses GSH to reduce hydrogen peroxide > water

GSH > GSSG

23
Q

vitamins

A
  1. C (absorbic acid)
  2. E
  3. A
24
Q

absorbic acid

vitamin C

A

reduces superoxide radicals and lipid peroxyl radicals

water soluble
important for recycle vitamin E
becomes a radical itself after donating

25
Q

vitamin E

A

alpha tocopherol (most effective form in humans and major form of E in diet)

lipid soluble, has membrane stabilizing activity

prevents damage from singlet oxygen, free radicals, lipid peroxidation

need vitamin c to recycle tocopherol radical back to alpha

26
Q

vitamin A

A

aka retinoid (animals) or beta-carotene (plants)

is lipid soluble

quenches vibration energy of singlet oxygen w/conjugated double bond system

27
Q

metabolic antioxidants

A
  1. glutathione (GSH)
  2. polyphenols/flavonoids
  3. uric acid
  4. bilirubin
28
Q

glutathione

GSH

A

glutamate + cysteine + glycine

donate electron = reactive
readily reacts w/ another GSH = GSSG (oxidized and inactive)

29
Q

glutathione

as co-factor

A

GPx uses GSH for hydrogen peroxide > water reduction = GSSG

GSSG is reduced by glutathione reductase w/NADPH from PPP

used by RBC to prevent oxidative damages

30
Q

polyphenols

flavonoids

A

found in plant extracts (green tea, grapes) red wine, dark chocolate

is water soluble

31
Q

uric acid

A

antioxidant in serum

32
Q

bilirubin

A

unconjugated bilirubin donate electron to radicals

lipid soluble

oxidation converts bilirubin > biliverdin

33
Q

antioxidant chain of reactions

A
  1. radical
  2. PUFA
  3. vitamin E
  4. vitamin C
  5. GSH
  6. NADPH (from PPP)

order of accepting electrons
PUFA = polyunsaturated fatty acid

34
Q

oxidative stress

definitions

A

irreversible damage caused by attack of ROS upon proteins/lipids/DNA of cells OR

from disbalance b/t ROS (pro-oxidants) and antioxidants

35
Q

RBC protectors

A
  1. PPP and reduced GSH, important for plasma membrane and hemoglobin
  2. glutathione peroxidase- destroys hydrogen and organic peroxides w/ reduced GSH, recovery by GSH reducatse
  3. methemoglobin reductase- reduces Fe3+ back to 2+ to recover hemoglobin, bhemoglobin is converted to methemoglobin w/ Fe3+ so cannot bind oxygen,
36
Q

lipid peroxidation

stress in cell membranes

A

hydroxyl radicals cause peroxidation of PUFAs = destroy integrity and function

hydroxyl radical + e from PUFA = lipid radical
lipid radical + oxygen = lipid peroxyl radical

-unstable so can get more electrons from PUFA = propagation, PUFA supply drained OR
-break down into malondialdehyde (mutagenic bc reacts w/ purines of DNA)

37
Q

lipid peroxidation defense

A
  1. vitamin E
  2. glutathione peroxidase- reduces lipid peroxides by convert to lipid alcohols
38
Q

stress in DNA

A

hydroxyl radicals =
double strand breaks in DNA (direct) OR
bind guanine to make 8-oxoguanine that needs repair (indirect)

Fall-Foundational Sciences Year 1 (33 decks)

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