Oxidative Stress

Question 1

What diseases can be caused by oxidative stress

Answer 1

Cardiovascular disease, COPD, Cancer, Pancreatitis, MS

Question 2

What are free radicals

Answer 2

An atom or molecule that contains one or more unpaired electrons
They are very reactive and take electrons from other atoms, molecules and ions

Question 3

How does a superoxide form

Answer 3

Addition of an electron to oxygen

Question 4

How is hydrogen peroxide formed

Answer 4

The addition of 2 hydrogen ions and an electron to a superoxide

Question 5

How does a hydroxyl radical form

Answer 5

The addition of an electron and hydrogen to hydrogen peroxide

Question 6

What are the 3 reactive oxygen species

Answer 6

Superoxide
Hydrogen peroxide
Hydroxyl radical

Question 7

What are the 2 nitrogen reactive species

Answer 7

Nitric oxide

Peroxynitrate

Question 8

How is peroxyntirite formed

Answer 8

Reaction of a superoxide and nitric oxide

Question 9

which is the most damaging free radical

Answer 9

hydroxyl radical

Question 10

how do reactive oxygen species damage DNA

Answer 10

• react with the bases leading to mispairing and mutation

- react with the sugar causing strand breakages and mutation

Question 11

the amount of what molecule can be used to measure oxidative damage

Answer 11

8-oxo-dG

Question 12

how do reactive oxygen species damage proteins

Answer 12

• by taking an electron from the backbone leading to fragmentation and degradation
• or the sidechain changing the protein structure which can either cause degradation, loss or gain in function

Question 13

how can disulphide bridges form due to ROS

Answer 13

if ROS take electrons from cysteine residues

Question 14

why can disulphide bonds disrupt function of a protein

Answer 14

as they cause misfolding and crosslinking

Question 15

how to ROS damage lipids

Answer 15

• extract a hydrogen atom from a polyunsaturated fatty acid on the membrane
• the lipid radical then reacts with oxygen to form lipid peroxyl radical
• these cause lipid peroxidation

Question 16

what is lipid peroxidation

Answer 16

a chain reaction of lipid peroxyl radicals stealing electrons off nearby fatty acids

Question 17

why does is the damage to lipids de to ROS dangerous

Answer 17

the lipid bilayer is disrupted and so membrane integrity fails

Question 18

give examples of exogenous sources of oxidants

Answer 18

radiation
pollutants
drugs
toxins

Question 19

true or false: anti malarial drugs are a source of exogenous oxidants

Answer 19

true

Question 20

give examples of endogenous oxidants

Answer 20

electron transport chain
nitric oxide synthases
NADPH oxidases

Question 21

how does the electron transport chain cause the production of oxidants

Answer 21

an electron may escape from the chain and react with dissolved oxygen to form a superoxide

Question 22

what are the 3 types of nitric oxide synthase

Answer 22

iNOS - inducible nitric oxide synthase
eNOS - endothelial nitric oxide synthase
nNOS - neuronal nitric oxide synthase

Question 23

what does nitric oxide synthase do

Answer 23

produces nitric oxide from arginine

Question 24

does nitric oxide synthase require NADPH?

Answer 24

yes and oxygen

Question 25

what does nitric oxide do

Answer 25

it is a signalling molecule which causes vasodilation, neurotransmission and is used in phagocytosis

Question 26

what is respiratory burst

Answer 26

rapid release of superoxide and hydrogen peroxide from phagocytes and peroxynitritie to destroy bacteria

Question 27

outline respiratory burst

Answer 27

- phagocyte produces superoxide from oxygen taking and electron from NADPH using NADPH oxidase - iNOS produces nitric oxide - nitric oxide combines with the superoxide to form peroxynitrite - superoxide also form hydrogen peroxide - hydrogen peroxide is converted into hypochlorite by myeloperoxidase - hypochlorite and peroxynitrate are used to kill bacteria

Question 28

what do genetic defects in NADPH oxidase cause

Answer 28

increased susceptibility to bacterial infections

Question 29

what does NADPH oxidase do

Answer 29

causes the production of superoxide from oxygen by adding an electron from NADPH

Question 30

what 2 enzymes defend against ROS

Answer 30

superoxide dismutase and catalase

Question 31

what does superoxide dismutase do

Answer 31

converts superoxide into hydrogen peroxide and oxygen

Question 32

what does catalase do

Answer 32

converts hydrogen peroxide into water and oxygen

Question 33

what does glutathione do

Answer 33

protects against oxidative damage as the cysteine residue donates an electron to the ROS and then reacts with another glutathione to form a disulphide

Question 34

what enzyme catalyses the disulphide bond formation in glutathione molecules

Answer 34

glutathione peroxidase

Question 35

what element does glutathione require

Answer 35

selenium

Question 36

how is the disulphide glutathione converted back

Answer 36

by the enzyme glutathione reductase which uses enzymes from NADPH

Question 37

where is the source of NADPH from for the production of glutathione

Answer 37

pentose phosphate pathway

Question 38

why are red blood cells more susceptible to oxidative stress

Answer 38

as the pentose phosphate pathway is the only NADPH production for these cells and so they cant produce lots of NADPH to reform glutathione

Question 39

what 2 vitamins are used to defend against ROS

Answer 39

vitamin E | vitamin C

Question 40

what does vitamin E do

Answer 40

lipid soluble | protects against lipid peroxidation

Question 41

what does vitamin C do

Answer 41

water soluble | regenerate reduced form of vitamin E

Question 42

what do free radical scavengers do

Answer 42

reduce free radical damage by donating hydrogen atoms and its electron to free radicals in nonenzymatic reactions

Question 43

give examples of free radical scavengers

Answer 43

vitamins E and C uric acid melanin

Question 44

what is oxidative stress

Answer 44

when there are more oxidants than antioxidants in the body

Question 45

what causes galactosaemia

Answer 45

deficiency of any of the following: - UDP galactose epimerase - uridyl transferase - galactokinase

Question 46

how do ROS contribute to galactosaemia

Answer 46

deficiency of an enzyme in galactose metabolism causes the accumulation of galactose. Aldose Reductase uses NADPH to convert galactose into Galactitol. this builds up to form cataracts

Question 47

what are symptoms of galactosaemia

Answer 47

cataracts, vomiting, renal failure, liver failure, brain damage

Question 48

why is a deficiency in uridyl transferase worse than for galactokinase

Answer 48

without uridyl transferase there is a build up of galactose 1P which accumulates in the brain, liver, kidneys preventing ATP production causing damage

Question 49

what is haemolysis

Answer 49

when protein damage causes aggregations of linked haemoglobin called Heinz bodies

Question 50

what are Heinz bodies a clinical signal of

Answer 50

G6PDH deficiency

Question 51

what do Heinz bodies do

Answer 51

bind to cell membranes of RBC making it harder to squeeze them through capillaries

Question 52

what organ removes Heinz bodies

Answer 52

spleen

Question 53

why does a G6PDH deficiency provide less protection from oxidative stress

Answer 53

less NADPH is produced so less glutathione is reformed so theres less protection

Question 54

what dangerous molecule builds up in a paracetamol overdose

Answer 54

NAPQI

Question 55

how does the body safely metabolise NAPQI

Answer 55

by conjugation with glutathione

Question 56

why does the bodies store of glutathione decrease

Answer 56

due to oxidative stress

Question 57

what antidote is used in paracetamol overdose

Answer 57

acetylcysteine which replenishes the bodies glutathione levels

Question 58

at a prescribed dosage how is paracetamol normally metabolised

Answer 58

in conjugation with sulphate or glucuronide