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32 Cards in this Set
- Front
- Back
Free Radical
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chemical compound with odd number of electrons
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Characteristics of free radical
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1. Extremely unstable and reactive
2. Consequence tendency 3. Free radicals have low chemical specificity 4. Results in chain reactions |
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Reactive oxygen species (ROS or ROI)
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- Non-ion, non-radical (H2O2)
- Ions (OCl-) -Ion-radicals (O2-, ROO-, OH-) |
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Enzymatice Formation of Free Radicals
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-byproduct of cellular respiration and metabolism
-phagocytic enzyme - prostaglandin synthesis - Cytochrome P450 (Liver) - Cells of the thyroid gland generate hydrogen peroxide |
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Cytochrome P450 system
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-in liver for drug and toxin removal
NADPH + H+ + O2 + RH NADP+ + H2O + R-OH |
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Externally generated free radicals
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- Exposure to abnormal environments such as hypoxia or hyperoxia
- Drugs, pesticides, anesthetics and industrial solvents - Interaction of ionizing radiation - Cigarette smoke, environmental pollutants, ultraviolet light & ozone |
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Physiological Functions of ROS and RNS
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- T4 Synthesis
- Bactericidal enzymes - Blood O2 levels - ventilation - erythropoietin production - Signal transduction - NO ion-> vasorelaxant - cellular maturation |
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Oxidative Stress
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- Highly toxic to cells
- Cell membrane damage - LIPID PERIOXIDATION - Direct attack of membrane proteins |
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LIPID PERIOXIDATION
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- ROS attacks unsaturated fatty acids in membrane phospholipids.
-Results in increase in membrane rigidity |
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ROS attack of membrane proteins
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- induces lipid-lipid, lipid-protein and protein-protein cross-linking, causing:
a.Decreased activity of membrane-bound enzymes (e.g. sodium pumps) b. Altered activity of membrane receptors c. Altered permeability |
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Diseases associtated with Oxidative Stress
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- Diabetes mellitus
- Chronic inflammation - Cancer - Arthrosclerosis -Cardiovascular accidents |
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diabetes mellitus
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- Mitochondrial oxidative stress
- affects insulin R’-> insulin resistance |
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Highly significant correlation between consumption of _____and ____ and death rate from certain cancers
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fats & oils
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Atherosclerosis
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- condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol
- Diet-derived lipids in the arterial wall and serum produce peroxides and other substances ->cell injury and produce changes in the arterial walls |
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Enzymatic antioxidants
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- Superoxide dismutase (SOD)
- H2O2 catalase - Glutathione reductase and peroxidase - Uric acid, bilirubin and ubiquinol |
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Dismutation
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A reaction or reactions involving two identical molecules in which one gains what the other loses
- Ie: an oxidation/reduction - speeds up a spontaneous reaction to reduce radical transition time |
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Inducible enzymes
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- An enzyme that is normally present in minute quantities within a cell, but whose concentration increases dramatically when a substrate compound is added.
- exposure to higher concentrations of O2 results in rapid increases in the SOD concentration |
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H2O2 catalase
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- Catalase is found in peroxisomes in eucaryotic cells.
- It degrades H2O2 to water and O2, and hence finishes the detoxification reaction started by SOD |
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Glutathione
[peroxidase & reductase] |
- Oxidized and reduced form of glutathione
- a Tripeptide - most important intracellular defense against damage by reactive oxygen species - degrades hydrogen peroxide |
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Glutathione reductase is oxidized to peroxidase by radicals. In a follow-up redox reaction, the reductase is regenerated. What molecule is the electron acceptor in the second reaction?
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- NADPH
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Antioxidant
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- a reducing agent
– a molecule stable enough to donate an electron to neutralize free radical, thus reducing its capacity to damage |
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Non-enzymatic antioxidants that protect cells from oxidant stress
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- Vit. E + Selenium
- Vit. C - Vit A |
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Vitamin E (alpha-tocopherol)
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- major lipid-soluble antioxidant
- Breaks the links that ROS have formed between fatty acid side chains in membrane lipids, thus protects membranes from oxidation -traps peroxy radicals in cellular membranes |
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What 2 molecules act synergistically as an antioxidant
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Vitamin E and selenium
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Vitamin C
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- most abundant water-soluble antioxidant in the body.
- Acts primarily in cellular fluid - Combats free-radical formation caused by pollution and cigarette smoke - Helps return vitamin E to its active form |
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Phagocytosis
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- engulfment of microorganisms, foreign particles, and cellular debris by WBC such as neutrophils and monocytes (macrophages)
- an important body defense mechanism |
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Chemotaxis
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need answer
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Diapedisis
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the outward passage of blood cells through intact vessel walls
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O2 independent system
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method of bacteriocide using pH changes inside the phagocytes and lysosomal enzymes
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O2 dependent system
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method of bacteriocide using the generation of free radicals
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Respiratory Burst
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– rapid consumption of O2 that accompanies the formation of O2.-.
- Catalyzed by NADPH oxidase (located in the WBC cell membrane.) |
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Deficiency in NADPH oxidase leads to what problem.
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- recurrent infections
- chronic granulomatous disease |