Antioxidants Flashcards
What are the five general strategies cells use to protect themselves from ROS damage?
- compartmentalization of free radical production
- metal sequestration
- repair processes
- defense enzymes
- endogenous and exogenous antioxidants
Where do we sequester the H2O2-producing enzymes in the body?
peroxisomes (which have a high content of antioxidant enzymes)
Why do we sequester the metals?
so they don’t undergo the fenton reaction (like Fe bound to ferritin)
What are three major defense enzymes that will convert ROS to nontoxic products?
superoxide dismutase, catalase, glutathione peroxidase
What ROS is removed by superoxide dismutase?
superoxide free radical
What ROS are removed by catalase and glutathione peroxidase?
hydrogen peroxide and lipid peroxides
Superoxide dismutations converts superoxide to what?
hydrogen peroxide and O2
Which defense enzyme is called the “primary defense” against oxidative stress?
superoxide dismutase because superoxide is such a strong initiator of chain reactions
Superoxide dismutase mutation is implicated in what disease?
familial ALS - about 5-10% of total ALS cases
What catalase turn hydrogen peroxide to?
water and O2
Where is catalase located in high concentrations?
in the peroxisomes, but also in the cytosol and microsomal cell fraction (Highest in kidney and liver where peroxisomal content is highest)
Catalse protects immune cells from what part of the immune response?
the respiratory burst
Glutathione can convert hydrogen peroxide to what and lipid peroxides to what?
H2O2 to water
lipid perosides to nontoxic alcohols
Glutathione peroxidases use what heavy metal?
selenium (the main reason we need some selenium in our diet)
Where in the cell is glutathione peroxidase mostly located?
cytosol and mitochondria
What enzyme will convert oxidized glutathione back to the sulfhydrul form? With what cofactor? From what pathway?
glutathione reductase with NADPH from PPP
WHat are antioxidants?
free radical scavengers that can terminate free radical chain reactions by donating electrons to ROS (usually nonenzymatically)
Why are nonenzymatic antioxidants capable of donating hydrogen groups without become radicals themselves?
They have aromatic rings structures that can deal with the loss of a hydrogen atom through resonance
What’s the most widely distributed antioxidant in nature?
vitamine E
What’s the most potent form of vitamin E?
alpha-tocapherol
vitamin E largely protects against what type of ROS?
lipid peroxidation in membranes
Although Vitamin E deficiency is rare, how does it present when it does occur?
hemolytic anemia due to fragility of RBCs
imbalance
myopathy
neurologic deficits due to degeneration of neurons
What’s ascorbic acid’s primary function in the body?
collagen synthesis, but also plays a role inf ree radical defense
How does reduced ascorbate work as an antioxidant?
It can generate the reduced form of vitamin E by donating electrons in the redox cycle - and the vitamin E does the majority of the antioxidant work
Is ascorbic acid water or lipid soluble?
water soluble - so it floats unbound in the blood and extracellular fluid so it can find the lipid bound vitamin E
What happens in vitamin C deficiency?
SCURVY: impaired wound healing, bleeding ecchymoses, swollen gums, anemia, enlargment and keratosis of hair follicles, lethargy, depression
Carotenoids are the precusors of what vitamin?
vitamin A
Carotenoids and vitamin A are capable of quenching what form of oxygen?
singlet oxygen (has no unpaired electrons in the outer orbitals but there is one orbital that is completely empty)
How does a vitamin A deficiency present?
it’s the number 1 cause of non-accidental blindness worldwide (especially night blindness)
follicular hyperkeratosis
xeropthalmia
What’s the general struture of the flavenoids?
contain two spatially separate aromatic fings
How do the flavenoids work? (4 ways)
- inhibit enzymes like xanthine oxidase that are responsible for superoxide anion production
- chelate Fe and Cu to prevent the fenton reaction
- donate electrons to superoxide or lipid peroxy radicals
- stabilize free radicals by complexing with them
What antioxidant accounts for the major free-radical trapping capacity of PLASMA?
Uric acid (with protein thiols) (note - it's also the highest concentration antioxidant in the blood)
Where in the body (not specifically the plasma) is uric acid most important for ROS protection?
the upper airways because there aren’t many other antioxidants there
What product from the pineal gland acts as an antioxidant?
melatonin
