Lecture 7 Flashcards
What is a free radical
A molecule with an unpaired electron
Name 3 substances that may form ROS (reactive oxygen species)
smog, cigarette smoke, immune response
Name two types of damage free radicals can form
DNA damage (eg nucleus, mitochondria) Damage to lipids (oxidation, cell membranes) Protein structure (amino acids, RBC)
What is an antioxidant
a substance that stops damaging effects of free radicals
name 5 antioxidant nutrients
Vitamins A, C, E, CoQ10, selenium
What are the 3 main endogenous antioxidants?
glutathione, CoQ10, super oxide dismutase, alpha-lipoic acid
Name 3 exogenous antioxidants
Vits A, C, E, lipoic acid
Which nutrients effectively ‘recycle’ each other?
ascorbate regenerates vitamin E
What are 5 types of reactive species?
- superoxide radical
- hydrogen peroxide
- hydroxyl radical
- peroxyl
- carbon centred radicals
How are oxygen centred radicals generated?
by oxygen reacting with different compounds (eg catcholamines (epinpehrines, norepinephrine, dopamine), or folate)
- the Electron transport chain produces them
- cytochrome P450
- activated blood cells during phaocytosis
Functions of antioxidants
- prevent breakdown of polyunsaturated lipids in cell membranes
- donate electrons to electron seeking compounds (preventing cell damage)
- stop oxidation but do not donate electrons
- reduce LDL oxidation
Which enzyme produces hydrogen peroxide while removing superoxide radicals?
superoxide dismutase
Which nutrient may also produce hydrogen peroxide while removing SOD radicals?
ascorbate
What cofactors does superoxide dismutase require?
Zn and Cu (extracellularly and cytoplasm), Mn (mitochondria)
What is the chemical eqn for Super oxide?
O2-
what form of ascorbate is formed when it reacts with SOD?
dehydroascorbate (DHAA)
What is hydrogen peroxide generated by?
SOD ascorbate Oxidation within peroxisomes trauma or injury amine oxidase
What is formed when hydrogen peroxide combines iwth superoxide radicals?
hydroxyl radical
What produces hydroxyl radicals
-gamma rays
-reactions between hydrogen peroxide and super oxide radicals
-
What is the haber-weiss reaction?
Reaction between super oxide radicals and hydrogen peroxide radicals that produces hydroxyl radicals.
What catalyses the haber-weiss reaction?
the reduction of ferric iron (Fe3+) to ferrous iron (Fe2+)
What are peroxyl, hydroperoxyl and alkoxyl radicals derived from?
superoxide radicals
What tissue are peroxyl, hydroperoxyl and alkoxyl radicals most common in and what do they cause?
fatty acid tissue, oxidation.
What substance still causes damage to cells but isn’t technically a free radical?
singlet oxygen
What generates singlet oxygen
lipid peroxidation enzyme reactions (eg respiratory burst) photochemical reactions (eg uv on oxygen).
How does singlet oxygen occur?
peripheral electron in the oxygen atom is excited to an orbital above the one it normally occupies.
What nutrient helps reduce superoxide radicals and what is the equation?
ascorbate (AH2) reduces superoxide to form hydrogen peroxide and dehydroascorbate (DHAA)
What nutrient reduces hydrogen peroxide radical?
ascorbate plus hydrogen peroxide goes to 2x water + dehydroascorbate (DHAA)
What enzyme reduces super oxide radical
super oxide dismutase (converts superoxide to hydrogen peroxide)
What enzymes reduce hydrogen peroxide and what cofactors are they dependent on
glutathione peroxidase (Se), catalase (haem Fe) and myeloperoxidase (haem fe)
What nutrients reduce hydroxyl radicals?
vitamin C (hydroxide to water, producing semidehydroascorbate) glutathione dihydrolipoic acid uric acid metallothionein CoQ10
What nutrients reduce peroxyl radicals
Vitamin E
Mn
CoQ10
Glutathione
What nutrients reduce singlet molecular oxygen
carotenoids
Vitamin C
lipoic acid
How do carotenoids deal with singlet molecular oxygen?
Absorb the energy and release it as heat
Which compounds regenerate Vitamin E?
ascorbate
Coenzyme Q10
glutathione (GSH - reduced form)
Which nutrients regenerate Vitamin C?
Niacin (B3 in coenzyme form NADH)
dihydrolipoic acid (reduced state) and lipoic acid (oxidised state)
glutathione
thioredoxin
What do two semi-dehydroascorbate produce
ascorbate + dehydroascorbate
What regenerates glutathione?
glutathione reductase (+ FAD cofactor) dihydrolipoic acid
What regenerates CoQ10?
dihydrolipoic acid
thioredoxin (+ FAD selenium dependent coenzyme)
Wha tnutrients does lipoic acid regenerate?
CoQ10, Vitamin C, Glutathione
Which two nutrients is glutathione peroxidase dependent on?
Se, Fe
Which nutrient recycles thioredoxin?
NADPH
