Nutrients, Oxidants, Antioxidants (Jenney) Flashcards
How are highly reactive oxygen radicals formed from O2?
When O2 accepts single electrons.
What are radicals?
Compounds that contain a single electron, usually at an outside orbital.
When does oxidative stress occur?
When the rate of ROS generation exceeds the capacity of the cell for their removal.
What is oxidative stress?
Increase in ROS levels that may result in significant damage to cell structures.
What is an oxidant?
Substance that is reduced and that, therefore, oxidizes the other component of an oxidation-reduction system.
What does an antioxidant do?
Stops propagation of free-radical damage in membranes.
Define ROS.
Chemically reactive molecules containing oxygen that are formed as a natural byproduct of the normal metabolism of oxygen.
What are some examples of ROS?
Superoxide (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH-dot)
Define RNS.
Family of antimicrobial molecules derived from nitric oxide and superoxide.
What are some examples of RNS?
Nitric oxide (NO), peroxynitrate (ONOO-)
What do reactive species do?
Directly damage DNA, RNA, proteins, sugars, lipids - everything!
Are they made purposefully or accidentally?
Both: purposefully by immune system, accidentally via many reactions in ETC in RBCs.
In what kind of reactions does iron act as an enzyme?
Catalysis, electron transfer, O2 transport
How is iron stored in the body?
In ferritin and hemosiderin - mostly in the liver.
Why are iron levels strictly regulated in the body?
To maintain a constant store.
Explain iron uptake via transferrin.
Target cells contain specific receptors. Tf-receptor complex is internalized by receptor-mediated endocytocis. Fe is released by acidification. Transferrin and receptor are recycled by exocytosis.
What substances inhibit non-heme uptake of iron?
Phytate & polyphenols in foods such as black tea and cocoa.
What substances stimulate uptake of iron?
Vitamin C (ascorbic acid), organic acids, heme
What is a hereditary defect that leads to iron excess?
Hemochromatosis
What is a diet-influenced condition that leads to iron excess (does have a genetic component)?
Hemosiderosis - excess alcohol consumption (especially red wine), excess iron supplementation by children
What are some causes of iron deficiency?
Anemia, infection (H. pylori - ulcers), vitamin deficiencies, inflammation
Is vitamin E lipid or water soluble?
Lipid, but does not accumulate in liver to toxic levels
Which vitamin can be found in vegetable oils, nuts, fish, and leafy green vegetables?
Vitamin E
If a patient comes in with a problem of fat malabsorption, which vitamin does he have low levels of?
Vitamin E
What is the main function of vitamin E?
Antioxidant - stop propagation of free-radical damage in membranes.
Is vitamin E deficiency common?
Not from diet, but rare genetic abnormalities or fat malabsorption maladies may cause it.
What are symptoms of vitamin E deficiency?
Pigmentosa, neurological symptoms (rate depends on level of ROS), may take years to develop if result from surgery or acquired fat malabsorption.
What vitamin can regenerate reduced vitamin E?
Vitamin C
Is vitamin C lipid or water soluble?
Water soluble
What are its reversibly oxidized and reduced forms?
Ascorbic acid & dehydroascorbic acid
How can vitamin C be regenerated?
By a number of different enzymes using electrons from NAD(P)H or glutathione.
What is the first thing oxidized by plasma when under oxidative stress?
Vitamin C
What happens when you have vitamin C deficiency?
Scurvy! Collagen needs vitamin C for proper development. Without it connective tissue in muscle, skin, and blood vessels is defective, leading to hemorrhagia, bleeding gums, weakness, and poor wound and bone healing. 10mg/day vitamin C can prevent this.
Vitamin C acts as a cofactor to how many enzymes?
At least 8 different enzymes
What happens when you consume megadoses of vitamin C?
Hypoglycemia, kidney stones, indigestion. Chewable supplements can dissolve tooth enamel. No direct evidence that megadoses cure colds or the flu.
What is the 2nd thing oxidized in stressed plasma?
Bilirubin - bound to albumin, along with uric acid
What is glutathione?
A small tripeptide that is reversibly oxidized/reduced. Good source of electrons to reduce ROS.
Is there any evidence that vitamin C or E supplements help fight disease?
2 separate studies out of many have these positive results: 1 - higher plasma vitamin C levels, and, to a lesser degree, fruit and vegetable intake were associated with a substantially decreased risk of diabetes. 2- daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.
What is the proposed mechanism for tumoricidal actions of pharmacological ascorbate?
Ascorbate distributes from the blood to the tumor ECF compartments after IV administration. In tumor interstitium, ascorbate is oxidized to ascorbate radical by a metalloprotein catalyst that ultimately forms tumoricidal effector H2O2. Pharmacologic ascorbate concentrations in plasma resulted in formation of both ascorbate radical and H2O2 in ECF - excess ascorbate can act as an oxidant in SOME tumore cells, but only in pharmacologic doses.
