40. Free Radical Physiology

Question 1

What is a free radical

Answer 1

Any species with one or more unpaired electron

Question 2

What is a reactive oxygen species

Answer 2

Broader category that can include free radicals

Includes radicals and non-radicals (however these can be easily converted into free radicals)

Question 3

What is superoxide

Answer 3

a key reactive oxygen species derived in msucle contraction)

Question 4

What other reactive species are there?

Answer 4

Reactive nitrogen species- includes nitrogen oxide which is improtant in vasodilation

Question 5

What can free radicals damage?

Answer 5

Nucleic acids

Nucleotides

Covalent bonds

Lipids

Membrane structures

Question 6

How are free radicals produced?

Answer 6

Contantly produced endogenously

Leaked from electron transport chains

Phagocytes create free radicals to breakdown invading organsims

Question 7

What are some exogenous sources of free radicals?

Answer 7

Ozone

Cigarrettes

Radiation

Pollution

Drugs

Diet

Question 8

How can oxygen become a free radical?

Answer 8

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.

Question 9

What systems in the cell can produce reactive oxygen species

Answer 9

Enzyme systems

Golgi apparatus

Peroxisomes (involved in beta-oxidisation)

Mitochondria

Sarcoplasmic reticulum

Xanthine oxidase produces superoxide in cytosol

Question 10

Why is superoxide dangerous?

Answer 10

Drives the fenton reaction which produces the hydroxyl radical.

Hydroxyl is a very reactive free radical

Question 11

What is the fenton reaction?

Answer 11

O2+- and H2O2 –> OH+ OH- O2

Catalysed by transition metals e.g. Fe2+ or Cu2+

Question 12

How do you detect free radicals?

Answer 12

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

Question 13

Explain the process of lipid peroxidation

Answer 13

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

Question 14

How can free radicals attack DNA?

Answer 14

Change to DNA bases leading to DNA alteration and change to the genetic message

Question 15

What are anti-oxidants

Answer 15

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

Question 16

Give some examples of anti-oxidants

Answer 16

Enzymes (glutathione peroxidase, superoxide dsmutase, catalase)

Metal binding proteins

Vitamin C (lipid soluble), E (water soluble) and carotenoids

Question 17

If anti-oxidants are there to stabilise the free radical, why dont they de-stabilise themselves

Answer 17

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

Question 18

What is oxidative stress?

Answer 18

Imbalance between potentially damaging free radical sand protective antioxidant defences

Antioxidants can cause reductase damage if they occur in too high numbers

Question 19

What is a good way of strudying oxidative stress in skeletal muscle?

Answer 19

Exercise

Naturally occcuring and required when homestasis is disturbed

The more exercise undertaken the more oxidative stress

Question 20

How do free radicals act during exercise?

Answer 20

Disrupt cell membranes

Cause muscle damage and soreness

Ischaemia- reperfusion injury

Changes in free radical activity due to immune response

Disruption of calcium homeostasis