Oxidative Stress

Question 1

What is the major driver of ageing?

Answer 1

Oxidative stress causes the most damage/stress in relationship to ageing.

Question 2

What is the free radical theory?

Answer 2

Oxygen is toxic chemically because it can form free radicals. This is occurs due to respiration.

Question 3

What is a free radical?

Answer 3

An uncharged molecule (typically highly reactive and short-lived) having an unpaired valency electron.

Question 4

Where are most free radical produced?

Answer 4

Mitochondria

Question 5

What is Reactive Oxygen Species (ROS)?

Answer 5

Oxygen-centred free radicals plus molecules that contribute to their formation.

Question 6

What is oxidative stress?

Answer 6

Oxidative stress is the imbalance between pro-and antioxidants in the cell, leading to accumulation of oxidative damage.

Question 7

What is the reactivity of superoxides?

Answer 7

High

Question 8

What is the reactivity of hydrogen peroxide?

Answer 8

Low

Question 9

What is the reactivity of the hydroxyl radical?

Answer 9

Very high

Question 10

What is the half-life of superoxides?

Answer 10

That is concentration dependent.

Question 11

What is the half-life of hydrogen peroxide?

Answer 11

Seconds to minutes

Question 12

What is the half life of hydroxyl radical?

Answer 12

Milliseconds

Question 13

What is superoxide soluble in?

Answer 13

Water

Question 14

What is hydrogen peroxide soluble in?

Answer 14

Water and lipids

Question 15

What are hydroxyl radicals soluble in?

Answer 15

Water

Question 16

What does a high reactivity mean for a free radical?

Answer 16

Shorter half life.

Question 17

Why is it important that superoxides are soluble in water?

Answer 17

They cannot cross membranes.

Question 18

What is important about hydrogen peroxide (H2O2)?

Answer 18

Although it has low reactivity however can travel around as it is soluble in water and lipids which means it can act as a messenger for reactive species.

Question 19

Why are hydroxyl radicals not a huge risk inside the body?

Answer 19

Such a small half life it wouldn’t have time to cause damage.

Question 20

Where is nitric oxide synthase?

Answer 20

Cytoplasm.

Question 21

Where are superoxides formed?

Answer 21

Inner matrix of the inner mitochondria.

Can also be other membrane bound organelle like exosomes.

Question 22

Why do superoxides accumulate?

Answer 22

Cannot cross membranes, so stays within the particle matrix.

Question 23

How is superoxide accumulation solved?

Answer 23

Superoxide dismutase (manganese centred) can convert them to hydrogen peroxide which can move through membranes.

Question 24

How is a hydrogen peroxide accumulation prevented?

Answer 24

A fentol reaction leads to a hydroxyl radical which then has a short half life and is broken down.

Question 25

What are antioxidants?

Answer 25

Cells primary defence against ROS.

Question 26

What kinds of antioxidants are there?

Answer 26

Enzymatic Non-enzymatic "scavengers" Metal chelators

Question 27

Examples of enzymatic antioxidants?

Answer 27

– Superoxide dismutases – Catalase – Glutathion peroxidases – Thioredoxins

Question 28

What kinds of non-enzymatic, "scavengers", antioxidants are there?

Answer 28

Lipid soluble Water soluble

Question 29

What kinds of lipid soluble, non-enzymatic "scavengers", antioxidants are there?

Answer 29

VitE Carotenoids Q10

Question 30

What kinds of water soluble, non-enzymatic "scavengers", antioxidants are there?

Answer 30

VitC GSH uric acid

Question 31

What is GSSG replenished by?

Answer 31

NADPH.

Question 32

What is GPI?

Answer 32

Detoxifying pathway.

Question 33

What are the cellular secondary defences of DNA repair?

Answer 33

Base excision repair (BER) Nucleotide excision repair (NER) Mismatch repair Double stranded break repair

Question 34

What kind of base excision repair (BER) are there?

Answer 34

Nuclear Mitochondrial Single strand break

Question 35

What kind of nucleotide excision repair (NER) are there?

Answer 35

Transcription- coupled Genome wide

Question 36

What kind of double strand break repair is there?

Answer 36

Non-homologous end joining Homologous recomination.

Question 37

What is XPD?

Answer 37

Helicase subunit of TF2H

Question 38

What is the function of XPD?

Answer 38

NER and transcription, mutated in trichodiodystrophy.

Question 39

What is XPA?

Answer 39

Necessary for NER but not for transcription

Question 40

What is protein turnover by chaperone-ubiquitin-proteasome system?

Answer 40

Damage proteins recognised by ligase ubiquitin activated, rest of protein moves onto the proteosome.

Question 41

What happens to protein turnover by chaperone-ubiquitin-proteasome system with age?

Answer 41

Can lose efficiency with age.

Question 42

What is the process of protein turnover by lysosomal system?

Answer 42

Recognises damaged organelle, encapsulates them in an autophagosome, organelle is degraded and its components are reused.

Question 43

What is the autophagosome?

Answer 43

Single membrane vesicle which fuses with the lysosome.

Question 44

What changes in protein turnover by lysosome?

Answer 44

Lysosomes get fuller until they become damaged and release lysosomal contents.

Question 45

What is the issue with old age lysosomes?

Answer 45

Contribute to cellular dysfunction.

Question 46

What is a telomere?

Answer 46

Define and protect the ends of all linear chromosomes, all animals have them.

Question 47

What happens to telomeres with age?

Answer 47

Shorten.

Question 48

Why do telomeres shorten with age?

Answer 48

Due to huge amounts of replication, oxidative stress induces this.

Question 49

What is important about telomeres?

Answer 49

Could be how we quantify ageing. Association with stress depending disaeses.

Question 50

What happens when you genetically modify polymerase gamma (polyG)?

Answer 50

Proofreading in ribosome is now not functioning. The information transcribed but it carries mistakes. Lowered the effect of ageing but more oxidative stress.

Question 51

Do antioxidants extend life?

Answer 51

No. They are good for you though.

Question 52

What is PRX?

Answer 52

peroxiredoxin

Question 53

What is SRX?

Answer 53

Sulfiredoxin

Question 54

What is SO2H

Answer 54

Sulfinic acid.