Increased action of following increases Free radical formation except: (AIPG 2011)
|A||Oxidative burst in phagocytes|
|D||Option B,C both of the above|
The principle free radicals (reactive Oxygen species) involved in cell injury include:
a. Superoxide anion b. Hydrogen peroxide c. Hydroxyl radical d. Peroxynitrite
GENERATION OF FREE RADICALS:
Inflammation, radiation, O2 toxicity, chemicals and reperfusion injury results in free radical formation, wherein following are mainly involved:
a. NADPH oxidase,
b. Oxidases in peroxisomes
c. Superoxide dismutase (SOD),
d. NO synthase and
e. Generation from H2O by hydrolysis [e.g. by radiation; Fenton reaction (from H2O2)].
The repiratory burst of activated macrophages is increased utilization of gucose via PentosePhosphate Pathway to reduce NADP+ and NADPH, and increased utilization of O2 to oxidase NAPDH to produce O2 radicals as cytotoxic agents to kill pagocytosed bacteria. The resiratorybusrt oxidase (NADPH oxidase) is a flavoprotien that reduced O2 to superoxide.
REMOVAL OF FREE RADICALS:
The major antioxidant enzymes (free radical scavenging systems) are:
i. Superoxide dismutase (SOD): a. In mitochondria b. Converts O2- (superoxide) → H2O2.
ii. Catalase: a. In peroxisomes b. Converts H2O2→ H2O+ O2.
iii. Glutathione Peroxidase:
a. In mitochondria. b. Converts –OH (hydroxyl radical) → H2O2 → H2O+ O2.
iv. Peroxiredoxins: a. Cause conversion to HNO2. b. In cytosol and mitochondria.
Free radicals may be generated within cells in several ways
a. The reduction-oxidation reactions that occur during normal metabolic processes.
b. Absorption of radiant energy (e.g., ultraviolet light, x-rays).
c. Rapid bursts of ROS are produced in activated leukocytes during inflammation. This occurs by a precisely controlled reaction in a plasma membrane multiprotein complex that uses NADPH oxidase for the redox reaction (i.e. oxidative burst in phagocytes)- .
d. Enzymatic metabolism of exogenous chemicals or drugs
e. Transition metals such as iron and copper
f. Nitric oxide (NO), an important chemical mediator generated by endothelial cells, macrophages, neurons, and other cell types, can act as a free radical () and can also be converted to highly reactive peroxynitrite anion (ONOO-) as well as NO2 and NO3-.
Removal of Free Radicals:
a. Free radicals are inherently unstable and generally decay spontaneously. , for example, is unstable and decays (dismutates) spontaneously into O2 and H2O2 in the presence of water.
b. In addition, cells have developed multiple nonenzymatic and enzymatic mechanisms to remove free radicals and thereby minimize injury.
c. These include the following:
d. Antioxidants either block the initiation of free radical formation or inactivate (e.g., scavenge) free radicals. Examples: lipid-soluble vitamins E and A as well as Vitamin C and glutathione in the cytosol.
e. As we have seen, iron and copper can catalyze the formation of ROS. The levels of these reactive metals are minimized by binding of the ions to storage and transport proteins (e.g., transferrin, ferritin, lactoferrin, and ceruloplasmin), thereby minimizing the formation of ROS.
f. A series of enzymes acts as free radical-scavenging systems and breaks down H2O2 and these enzymes are located near the sites of generation of the oxidants and include the following:
a. Catalase, present in peroxisomes, decomposes H2O2 (2H2O2 → O2 + 2H2O).
b. Superoxide dismutases (SODs)------are found in many cell types and convert oxygen free radical to H2O2.
c. Glutathione peroxidase------also protects against injury by catalyzing free radical breakdown (H2O2 + 2GSH →GSSG [glutathione homodimer] + 2H2O, or 2OH + 2GSH →GSSG + 2H2O). The intracellular ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) is a reflection of the oxidative state of the cell and is an important indicator of the cell's ability to detoxify ROS.