What are free radicals?
Highly reactive molecules because of unpaired electrons
What is the benefit of free radicals in the body?
Attack foreign bacteria and viruses
What are the negative effects of free radicals in the body?
- Alter functions of proteins/enzymes
- Alter DNA
- Oxidize LDL leading to higher risk of cardiovascular disease
What is a free radical containing oxygen called?
Reactive oxygen species (ROS).
How are free radicals generated?
Byproducts of aerobic metabolism, sunlight exposure, smoking, alcohol consumption, environmental pollution and body processes.
Where in the cell are free radicals formed?
Extracellular fluid (ECF), cytoplasm, membrane
Oxygen-centered radical formed by electrons leaking out of ETC. Formed with a single electron is added to oxygen.
Superoxide radical
How are white blood cells responsible for generating superoxide radicals?
Respiratory burst
Removal of bacteria/viruses
How do superoxide radicals form other reactive species such as hydrogen peroxide or hydroperoxyl?
Initiator of chain reactions
What is characteristic of superoxide radical?
Do not diffuse too far from source of origin (mitochondria and some cytosol)
Not considered a radical but a ROS.
Hydrogen peroxide (H2O2)
What reactions generate H2O2?
Ascorbate elimination of superoxide
Reactions in what organelle can generate H2O2?
Peroxisomes
Under what circumstances do peroxisomes generate H2O2?
Trauma and injury
Enzyme responsible for the generation of H2O2
Superoxide dismutase (SOD)
Reacts with SOD to form hydroxyl radical
H2O2
How does H2O2 cause damage?
Easily diffuses in water and lipids
Superoxide dismutase two mechanisms are
Extracellular and cytosolic SOD (requires zinc and copper)
Mitochondrial SOD (manganese dependent)
What is the function of superoxide dismutase?
Converts superoxide radicals into hydrogen peroxide
Superoxide can be broken down by
Vitamin C
Mechanism that breaks down superoxide to a less damaging form
SOD mechanism
What form of SOD reacts with superoxide ion to form oxygen?
Oxidized
What is generated with oxidized SOD reacts with superoxide ion (O2-)
Reduced form of enzyme
What does the reduced form of SOD react with to form H2O2?
Superoxide ion and 2 protons from hydrogen
What happens when another superoxide reacts with 2 protons to form H2O2?
Regeneration of oxidized SOD
Oxygen-centered radical generated through exposure to gamma rays and low wavelength electromagnetic radiation. Major initiator of lipid peroxidation. Most potent radical.
Hydroxyl radical
Hydroxyl radical is generated in reactions involving
Reactive species, electrons, protons
What parts of the cell are most susceptible to damage by hydroxyl radical?
Membrane and DNA
What are hydroxyl radicals major initiators of?
Lipid peroxidation
What do hydroxyl radicals react with?
Nucleic acids and proteins
What happens when free radicals attack DNA/RNA?
Additions and deletions of specific proteins.
What happens when free radicals attack proteins?
Impaired cell function and inflammatory response
When vitamin C is consumed in excess, generally the excess is:
Excreted in the urine
Vitamin C megadoses can increase the risk of
Kidney stones
Vitamin C acts as a cofactor by maintaining iron in a reduced state in:
Collagen synthesis
Although excess absorbed ascorbic acid is excreted in urine, the body has an estimated maximal body pool of ______ which can be maintained with intakes of 100mg of vitamin C per day
1500mg
Which water-soluble vitamin contributes to "intracellular cement" in the formation of scar tissue and wound healing?
Vitamin C
Which of the following molecules synthesized with the help of vitamin C underscores the importance of vitamin C to fat metabolism?
Carnitine
A primary function of vitamin C is to act as an:
Antioxidant
Ascorbic acid acts as a pro-oxidant by:
Mobilizing ferric iron storage
Elevated homocysteine levels can be due to all the following except
- Low folacin
- low cobalamin
- low pyridoxine
The primary role of vitamin C is as a reducing agent, particularly for the mineral component of a number of enzymes that become oxidized following a catalysis of a reaction
True
High circulating levels of homocysteine have been implicated in a number of pathologies including CVD
True
Vitamin C is a good reducing agent, meaning it keeps things reduced by undergoing irreversible oxidation; thus, it must continuously be replaced with dietary sources
False, oxidation is not reversible, can be recycled back to its reduced form.
Ascorbic acid can provide electrons reduce the superoxide radical to form
Hydrogen peroxide and DHAA (dehydroascorbic acid)
Oxidized form of ascorbic acid
Dehydroascorbic acid (DHAA)
Ascorbic acid reacts with the hydroxyl radical to produce
Water and unreactive semidehydroascorbate radical
Key step in the formation of a collagen fibril
Hydroxylation of selected prolines and lysines
Where in the cell does the formation of collagen fibril occur:
E.R/golgi compartment, secretory vesicles, and plasma membrane
Which tocopherol form provides the most vitamin E activity in the U.S. food supply?
Alpha
A genetic deficiency in ____ leads to a vitamin E deficiency syndrome
Tocopherol carrier protein in the jejunum
Which fat-soluble vitamin has as its principal function the maintenance of membrane integrity?
Vitamin E
In what type of tissue is the largest amount of vitamin E stored?
Adipose
Which compound is associated with less oxidized LDL and less risk of development of foam cells and atherosclerotic lesions?
Alpha-tocopherol
Which vitamin is associated with improved plasma membrane structure and glucose transport/metabolic control in people with type 2 diabetes?
Vitamin E
For which vitamin is the tolerable upper intake level set because of increased tendency for bleeding?
Vitamin E
Where would you find retinoid X receptors (RXR)?
Nucleus
Immediately following a balanced meal that contained vitamin E (such as fortified milk), where would you most likely find most of the vitamin E in the body?
In chylomicrons in the lymphatics and general circulation
How is the alpha-tocopherol radical regenerated?
Pentose phosphate pathway regenerates GSSG thioredoxin (oxidized) lipoate which regenerates ascorbate monoanion which regenerates alpha-tocopherol radical.
Which of the carotenoid pigments has the greatest vitamin A activity?
Beta-carotene
Which is the strongest antioxidant?
Lycopene
Essential trace element. Major role as co-factor of enzymes such as Glutathione Peroxidase (GPX)
Selenium
What is the reduced form of Glutathione?
GSH
What is the oxidized form of Glutathione?
GSSG
Enzyme that works with Glutathione. Selenium-dependent. Important in phagocytic cells like macrophages (oxidative destruction)
Glutathione peroxidase (GPX)
What happens if there is not enough Selenium?
GPS is not functional. Reactions cannot occur.
Describe the catalytic cycle of GPX
Selenolate reduced to selenic acid, combines with glutathione forms a selenosulfide complex, with another glutathione active form is regenerates forming GSSG
Enzyme that gets rid of GSSG
Glutathione reductase
Which antioxidant is the most effective in rapidly eliminating hydroxyl radicals prior to initiation of oxidative damage?
Vitamin C
Name the top-selling herbs in America
- Echinacea
- Garlic
- Gingko biloba
- Ginseng
- Milk Thistle
- St. John's Wort
Phytochemicals are
Non-nutrient plant compounds that are biologically active
The kind and amount of phytochemicals in plants varies with
Environmental conditions during plant growth, stage or ripeness and storage conditions.
Flavonoids are phytochemicals that can function in the body as:
Antioxidants
Soy is rich in:
Isoflavones
What are suggested health benefits of carotenoids?
Reduce risk of certain cancers, cardiovascular disease and age-related eye disorders.
What is the largest category of phytochemicals?
Flavonoids
Suggested health benefits of flavonoids
Protect against cancer and cardiovascular disease
What are indoles and alliums?
Sulfur-containing phytochemicals found in cruciferous vegetable, garlic, onions, leeks and shallots.
What is the main function of indoles?
Inactivate estrogen
What is the main function of alliums?
Boost the activity of cancer-destroying enzymes and prevent gut bacteria from converting nitrates to nitrites.
What are phytoestrogens?
Phytochemicals found in soybeans, flaxseed and barley. Include isoflavones and lignins.
Suggested function and health benefit
- Blocking estrogen receptors
- May protect against certain cancers and osteoporosis.
Interactions have been reported between gingko biloba and:
Aspirin and warfarin
Regulation of herbal supplements in the United States
Falls under the Dietary Supplement Herbal and Education Act of 1994