Antioxidants Flashcards
What are Reactive Oxygen Species?
toxic by-products of oxygen metabolism
Name some ROS:
Superoxide
Hydrogen peroxide
Hydroxyl radical
Nitric oxide
What is Oxidative Stress?
production of ROS is greater than the antioxidant defenses can consume them
Ischemia-Reperfusion Injury
most tissue damage occurs on re-exposure to oxygen after cardiac infarct or other ischemic event
ROS are believed to be involved in what diseases?
Cancer - oxidative damage to DNA
Atherosclerosis - ox of low density lipoprotein and its uptake by macrophages
Alzheimer’s disease - neuronal death from elevated NO and/or mitochondrial dysfunction
Aging - progressive decline in mitochondrial function
Vitamin E is what type of Antioxidant?
lipophilic
functions as a chain-breaking antioxidant that prevents propagation of the lipid carbon centered radicals of the Fatty Acid residues of membranes
What foods contain Vitamin E?
grains
wheat germ
nuts
vegetable oils
Vitamin E may contain a variety of ___ and ___ .
Tocopherols (w saturated side chains)
Tocotrienols (w 3 double bonds in side chains)
The tocopherol with the highest activity and is often called “natural” vitamin E
alpha-tocopherol
Absorption of Vitamin E:
where?
where does it go?
in what form?
Absorbed in the intestine and transferred to the liver
Chylomicrons (plasma lipoproteins)
Does Vitamin E protect against heart disease?
No good evidence.
Supplements not currently recommended.
Problem with ingesting too much Vitamin E?
Can compete with Vitamin K absorption (potential problem with anticoagulants).
The TUL is 1000 mg/day so other than that it is not very toxic despite being fat soluble.
Tolerable upper limit of Vitamin E
1000 mg/day
Recommended Dietary Allowance (RDA) for Vitamin E
15 mg/day
So, Vitamin E is important for protecting molecules in what type of environment? Hydrophilic/phobic
Example of where…
Hydrophobic environments
CNS
Vitamin C is an example of what type of Antioxidant?
What makes it special?
Hydrophilic
Can be oxidized to other forms of the vitamin making it the major hydrophilic antioxidant
Relationship between Vitamin C and Vitamin E?
Vitamin C returns Vitamin E to its reduced form, so indirectly impacts the oxidation of the membrane
Evidence for the benefits of Vit C?
Lowered markers of…
DNA oxidation
membrane oxidation
Some evidence of lowering risk of... heart disease cancer cataracts protection for smokers
Vitamin C is also important for ____ synthesis, deficiency results in ____ as seen in pirates.
collagen synthesis
scurvy
also, deficiency causes slow wound healing
Another important role of Vit C, is that it aids in the absorption of ____
Iron
by reducing ferric iron to ferrous iron
Toxicity of Vitamin C?
Low - some advocate massive doses (30-60 times RDA of 75 mg/day)
What foods are good sources of Vit C?
citrus fruits, tomatoes, green peppers, broccoli, and other vegetables
Antioxidant Enzymes include (3):
Glutathione peroxidases
Superoxide dismutases
Catalases
Glutathione peroxidase..action
catalyzes the reduction of hydrogen peroxide by glutathionine
(oxidized glutathionine is red by glutathione reductase which uses NADPH)
Selenium - at the active site, essential but not an antioxidant itself
Selenium is found in two antioxidant enzymes:
Glutathione peroxidase
Thioredoxin reductase
So Selenium is an essential Antioxidant?
No.
Essential but not an Antioxidant.
Required for:
Glutathione peroxidase
Thioredoxin reductase
Superoxide dismutase
dismutation of superoxide -> hydrogen peroxide + O2
mammals have at least two isozymes
Catalases
dismutation of hydrogen peroxide -> water and oxygen
a hemoprotein found in peroxisomes (normally the site of most, if not all, H2O2 generating rxns)
Flavonoids and Flavones are what type of Antioxidant?
Hydrophilic antioxidants
Just like Vitamin C
What foods are Flavonoids and Flavones found in?
green tea, red wine, cocoa
What potential benefits do Flavonoids and Flavones have?
possibly reducing cardiovascular disease and cancer
What are some of the effects of Selenium?
Prevention of purine oxidation (measure of purine oxidation = 8-oxoguanine production)
Selenomethionine in thioredoxin activates the tumor suppressor protein
Grave’s Disease patients by preventing deterioration of vision
Describe the two Isozymes of Superoxide Dismutase.
1) Cytoplasmic: active site copper and zinc
—-genetic deficiency in Cu/Zn enzyme =>amylotrophic lateral sclerosis (Lou Gehrigs)
2) Mitochondrial: active site manganese.
Note: Extracellular forms may also exist.
Vitamin ___ would be expected to be most effective against ROS found in the cytosol while Vitamin ___ would be useful for neutralizing ROS that are located in membranes.
Vitamin C - cytosol (hydrophilic)
Vitamin E - membrane (hydrophobic)
T / F - Metal ions promote oxidation.
Iron promotes oxidation of lipids and other compounds.
But are more examples of metal ions that promote reduction by helping antioxidant enzymes.
Ex:
selenium (involved with glutathione peroxidase)
copper and zinc (which are components of superoxide dismutase)
Other metal ions, like Ca or Mg, probably have no effect one way or the other.
What is 8-Oxoguanine?
An oxidation product of the base guanine.
Results from catabolism of DNA/RNA followed by Oxidation.
Marker of DNA Oxidation
What is Dismutation?
Dismutation is a molecular rearrangement in which one part of a molecule is oxidized and another is reduced.
Ex; superoxide dismutase
Benefits of Antioxidant Supplementation?
No evidence; But evidence for the benefit of Antioxidant rich food is real.
What food contains more Antioxidants than any other fruit or vegetable?
Blueberries
