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32 Cards in this Set

  • Front
  • Back
Free Radical
chemical compound with odd number of electrons
Characteristics of free radical
1. Extremely unstable and reactive
2. Consequence tendency
3. Free radicals have low chemical specificity
4. Results in chain reactions
Reactive oxygen species (ROS or ROI)
- Non-ion, non-radical (H2O2)
- Ions (OCl-)
-Ion-radicals (O2-, ROO-, OH-)
Enzymatice Formation of Free Radicals
-byproduct of cellular respiration and metabolism
-phagocytic enzyme
- prostaglandin synthesis
- Cytochrome P450 (Liver)
- Cells of the thyroid gland generate hydrogen peroxide
Cytochrome P450 system
-in liver for drug and toxin removal

NADPH + H+ + O2 + RH  NADP+ + H2O + R-OH
Externally generated free radicals
- 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
Physiological Functions of ROS and RNS
- T4 Synthesis
- Bactericidal enzymes
- Blood O2 levels
- ventilation
- erythropoietin production
- Signal transduction
- NO ion-> vasorelaxant
- cellular maturation
Oxidative Stress
- Highly toxic to cells
- Cell membrane damage
- LIPID PERIOXIDATION
- Direct attack of membrane proteins
LIPID PERIOXIDATION
- ROS attacks unsaturated fatty acids in membrane phospholipids.
-Results in increase in membrane rigidity
ROS attack of membrane proteins
- 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
Diseases associtated with Oxidative Stress
- Diabetes mellitus
- Chronic inflammation
- Cancer
- Arthrosclerosis
-Cardiovascular accidents
diabetes mellitus
- Mitochondrial oxidative stress
- affects insulin R’-> insulin resistance
Highly significant correlation between consumption of _____and ____ and death rate from certain cancers
fats & oils
Atherosclerosis
- 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
Enzymatic antioxidants
- Superoxide dismutase (SOD)
- H2O2 catalase
- Glutathione reductase and peroxidase
- Uric acid, bilirubin and ubiquinol
Dismutation
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
Inducible enzymes
- 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
H2O2 catalase
- Catalase is found in peroxisomes in eucaryotic cells.
- It degrades H2O2 to water and O2, and hence finishes the detoxification reaction started by SOD
Glutathione
[peroxidase & reductase]
- Oxidized and reduced form of glutathione
- a Tripeptide
- most important intracellular defense against damage by reactive oxygen species
- degrades hydrogen peroxide
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?
- NADPH
Antioxidant
- a reducing agent
– a molecule stable enough to donate an electron to neutralize free radical, thus reducing its capacity to damage
Non-enzymatic antioxidants that protect cells from oxidant stress
- Vit. E + Selenium
- Vit. C
- Vit A
Vitamin E (alpha-tocopherol)
- 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
What 2 molecules act synergistically as an antioxidant
Vitamin E and selenium
Vitamin C
- 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
Phagocytosis
- engulfment of microorganisms, foreign particles, and cellular debris by WBC such as neutrophils and monocytes (macrophages)
- an important body defense mechanism
Chemotaxis
need answer
Diapedisis
the outward passage of blood cells through intact vessel walls
O2 independent system
method of bacteriocide using pH changes inside the phagocytes and lysosomal enzymes
O2 dependent system
method of bacteriocide using the generation of free radicals
Respiratory Burst
– rapid consumption of O2 that accompanies the formation of O2.-.
- Catalyzed by NADPH oxidase (located in the WBC cell membrane.)
Deficiency in NADPH oxidase leads to what problem.
- recurrent infections
- chronic granulomatous disease