40. Free Radical Physiology Flashcards
What is a free radical
Any species with one or more unpaired electron
What is a reactive oxygen species
Broader category that can include free radicals
Includes radicals and non-radicals (however these can be easily converted into free radicals)
What is superoxide
a key reactive oxygen species derived in msucle contraction)
What other reactive species are there?
Reactive nitrogen species- includes nitrogen oxide which is improtant in vasodilation
What can free radicals damage?
Nucleic acids
Nucleotides
Covalent bonds
Lipids
Membrane structures
How are free radicals produced?
Contantly produced endogenously
Leaked from electron transport chains
Phagocytes create free radicals to breakdown invading organsims
What are some exogenous sources of free radicals?
Ozone
Cigarrettes
Radiation
Pollution
Drugs
Diet
How can oxygen become a free radical?
When Oxyegn is reduced it forms oxygen singlet
1-3%(debated) of the oxygen reduced in the electron transport chain can leak into the body.
What systems in the cell can produce reactive oxygen species
Enzyme systems
Golgi apparatus
Peroxisomes (involved in beta-oxidisation)
Mitochondria
Sarcoplasmic reticulum
Xanthine oxidase produces superoxide in cytosol
Why is superoxide dangerous?
Drives the fenton reaction which produces the hydroxyl radical.
Hydroxyl is a very reactive free radical
What is the fenton reaction?
O2+- and H2O2 –> OH+ OH- O2
Catalysed by transition metals e.g. Fe2+ or Cu2+
How do you detect free radicals?
Measure indicators of free radicals
MDA
Ethane
Pentane
F2- isoprostanes- gold standard of lipid peroxidation
Measure anti-oxidants
Not an exact science for skeletal muscles
Explain the process of lipid peroxidation
Unsaturated lipids are attacked by lipid peroxidation losing hydrogen ions.
In the prescence of oxygen hydroperoxide is created due to molecular re-arrangement in the de-stabilised lipid
This creates a chain reaction
How can free radicals attack DNA?
Change to DNA bases leading to DNA alteration and change to the genetic message
What are anti-oxidants
Prevent initaiton of an oxidation reaction by scavenging
They also bind transition metals that catalase free radical porduction
Break the chain of free radicals e.g. lipid oxididsation
Give some examples of anti-oxidants
Enzymes (glutathione peroxidase, superoxide dsmutase, catalase)
Metal binding proteins
Vitamin C (lipid soluble), E (water soluble) and carotenoids
If anti-oxidants are there to stabilise the free radical, why dont they de-stabilise themselves
The anti-oxidants structure allows them through there chemical composition to be stable whilst losing an electron
e.g. they will cycle an electron around there structure
What is oxidative stress?
Imbalance between potentially damaging free radical sand protective antioxidant defences
Antioxidants can cause reductase damage if they occur in too high numbers
What is a good way of strudying oxidative stress in skeletal muscle?
Exercise
Naturally occcuring and required when homestasis is disturbed
The more exercise undertaken the more oxidative stress
How do free radicals act during exercise?
Disrupt cell membranes
Cause muscle damage and soreness
Ischaemia- reperfusion injury
Changes in free radical activity due to immune response
Disruption of calcium homeostasis
