Oxidative Stress Flashcards
What is the major driver of ageing?
Oxidative stress causes the most damage/stress in relationship to ageing.
What is the free radical theory?
Oxygen is toxic chemically because it can form free radicals. This is occurs due to respiration.
What is a free radical?
An uncharged molecule (typically highly reactive and short-lived) having an unpaired valency electron.
Where are most free radical produced?
Mitochondria
What is Reactive Oxygen Species (ROS)?
Oxygen-centred free radicals plus molecules that contribute to their formation.
What is oxidative stress?
Oxidative stress is the imbalance between pro-and antioxidants in the cell, leading to accumulation of oxidative damage.
What is the reactivity of superoxides?
High
What is the reactivity of hydrogen peroxide?
Low
What is the reactivity of the hydroxyl radical?
Very high
What is the half-life of superoxides?
That is concentration dependent.
What is the half-life of hydrogen peroxide?
Seconds to minutes
What is the half life of hydroxyl radical?
Milliseconds
What is superoxide soluble in?
Water
What is hydrogen peroxide soluble in?
Water and lipids
What are hydroxyl radicals soluble in?
Water
What does a high reactivity mean for a free radical?
Shorter half life.
Why is it important that superoxides are soluble in water?
They cannot cross membranes.
What is important about hydrogen peroxide (H2O2)?
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.
Why are hydroxyl radicals not a huge risk inside the body?
Such a small half life it wouldn’t have time to cause damage.
Where is nitric oxide synthase?
Cytoplasm.
Where are superoxides formed?
Inner matrix of the inner mitochondria.
Can also be other membrane bound organelle like exosomes.
Why do superoxides accumulate?
Cannot cross membranes, so stays within the particle matrix.
How is superoxide accumulation solved?
Superoxide dismutase (manganese centred) can convert them to hydrogen peroxide which can move through membranes.
How is a hydrogen peroxide accumulation prevented?
A fentol reaction leads to a hydroxyl radical which then has a short half life and is broken down.
What are antioxidants?
Cells primary defence against ROS.
What kinds of antioxidants are there?
Enzymatic
Non-enzymatic “scavengers”
Metal chelators
Examples of enzymatic antioxidants?
– Superoxide dismutases
– Catalase
– Glutathion peroxidases
– Thioredoxins
What kinds of non-enzymatic, “scavengers”, antioxidants are there?
Lipid soluble
Water soluble
What kinds of lipid soluble, non-enzymatic “scavengers”, antioxidants are there?
VitE
Carotenoids
Q10
What kinds of water soluble, non-enzymatic “scavengers”, antioxidants are there?
VitC
GSH
uric acid
What is GSSG replenished by?
NADPH.
What is GPI?
Detoxifying pathway.
What are the cellular secondary defences of DNA repair?
Base excision repair (BER)
Nucleotide excision repair (NER)
Mismatch repair
Double stranded break repair
What kind of base excision repair (BER) are there?
Nuclear
Mitochondrial
Single strand break
What kind of nucleotide excision repair (NER) are there?
Transcription- coupled
Genome wide
What kind of double strand break repair is there?
Non-homologous end joining
Homologous recomination.
What is XPD?
Helicase subunit of TF2H
What is the function of XPD?
NER and transcription, mutated in trichodiodystrophy.
What is XPA?
Necessary for NER but not for transcription
What is protein turnover by chaperone-ubiquitin-proteasome system?
Damage proteins recognised by ligase ubiquitin activated, rest of protein moves onto the proteosome.
What happens to protein turnover by chaperone-ubiquitin-proteasome system with age?
Can lose efficiency with age.
What is the process of protein turnover by lysosomal system?
Recognises damaged organelle, encapsulates them in an autophagosome, organelle is degraded and its components are reused.
What is the autophagosome?
Single membrane vesicle which fuses with the lysosome.
What changes in protein turnover by lysosome?
Lysosomes get fuller until they become damaged and release lysosomal contents.
What is the issue with old age lysosomes?
Contribute to cellular dysfunction.
What is a telomere?
Define and protect the ends of all linear chromosomes, all animals have them.
What happens to telomeres with age?
Shorten.
Why do telomeres shorten with age?
Due to huge amounts of replication, oxidative stress induces this.
What is important about telomeres?
Could be how we quantify ageing.
Association with stress depending disaeses.
What happens when you genetically modify polymerase gamma (polyG)?
Proofreading in ribosome is now not functioning.
The information transcribed but it carries mistakes.
Lowered the effect of ageing but more oxidative stress.
Do antioxidants extend life?
No. They are good for you though.
What is PRX?
peroxiredoxin
What is SRX?
Sulfiredoxin
What is SO2H
Sulfinic acid.
