Oxidative Stress and Antioxidants

Question 1

free radical

Answer 1

atom/molecule/ion with an unpaired valence electron

aka ROS

Question 2

superoxide

Answer 2

oxygen gains an electron

not very reactive, can be used as second messanger

Question 3

hydrogen peroxide

Answer 3

H202
reactive, second messangers

Question 4

hydroxyl radical

Answer 4

most reactive and dangerous

3 electrons added to oxygen

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

Question 5

sources of ROS

Answer 5

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

Question 6

mitochondrial ETC

Answer 6

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

Question 7

cytochrome p450 oxidase

normal mechanism

Answer 7

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

Question 8

MEOS and alcohol induced liver damage

Answer 8

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

Question 9

skin lesions in PCT

responsible

Answer 9

uroporphyrins NOT MEOS

light gets absorbed then energy is transferred to oxygen = ROS

Question 10

NADPH-dependent oxidase

Answer 10

in phagocytic cells

gets activated by inflamation from bacterial infections

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

good thing

Question 11

chronic granulomatosis disease

Answer 11

deficiency in NADPH oxidase = respiratory burst compromised

inc susceptibility to bacterial and fungal infections

Question 12

xanthine oxidase

Answer 12

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

Question 13

iron and copper ions

Answer 13

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)

Question 14

fenton reaction

Answer 14

iron + superoxide radical + hydrogen peroxide = hyroxyl radicals

Question 15

hereditary hemochromatosis

Answer 15

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

Question 16

iron overload

other causes

Answer 16

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

frequent blood transfusions

Question 17

radiation

Answer 17

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

Question 18

antioxidant categories

Answer 18

antioxidative enzymes
vitamins
metabolic antioxidants

Question 19

antioxidative enzymes

Answer 19

1. superoxide dismutase
2. catalase
3. glutathione peroxidase

Question 20

superoxide dismutase

SOD

Answer 20

converts superoxide radical > hydrogen peroxide

Question 21

catalase

Answer 21

detoxifies hydrogen peroxide > water

heme containing enzyme in peroxisomes

Question 22

glutathione peroxidase

Answer 22

detox hydrogen peroxide and lipid peroxidases

uses GSH to reduce hydrogen peroxide > water

GSH > GSSG

Question 23

vitamins

Answer 23

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

Question 24

absorbic acid

vitamin C

Answer 24

reduces superoxide radicals and lipid peroxyl radicals

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

Question 25

vitamin E

Answer 25

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

Question 26

vitamin A

Answer 26

aka retinoid (animals) or beta-carotene (plants) is lipid soluble quenches vibration energy of singlet oxygen w/conjugated double bond system

Question 27

metabolic antioxidants

Answer 27

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

Question 28

glutathione | GSH

Answer 28

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

Question 29

glutathione | as co-factor

Answer 29

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

Question 30

polyphenols | flavonoids

Answer 30

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

Question 31

uric acid

Answer 31

antioxidant in serum

Question 32

bilirubin

Answer 32

unconjugated bilirubin donate electron to radicals lipid soluble oxidation converts bilirubin > biliverdin

Question 33

antioxidant chain of reactions

Answer 33

1. radical 2. PUFA 3. vitamin E 4. vitamin C 5. GSH 6. NADPH (from PPP) | order of accepting electrons PUFA = polyunsaturated fatty acid

Question 34

oxidative stress | definitions

Answer 34

irreversible damage caused by attack of ROS upon proteins/lipids/DNA of cells OR from disbalance b/t ROS (pro-oxidants) and antioxidants

Question 35

RBC protectors

Answer 35

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,

Question 36

lipid peroxidation | stress in cell membranes

Answer 36

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)

Question 37

lipid peroxidation defense

Answer 37

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

Question 38

stress in DNA

Answer 38

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