Role of Reactive Oxygen Species in Cellular Injury PDF

**Role of reactive oxygen species in cellular injury**. Several molecular structures are generated during cellular injury that can damage membranes, proteins, and nucleic acids. A number of inherent antioxidant compounds are present within the cell to limit the damage. Cellular injury due to reacti...

**Role of reactive oxygen species in cellular injury**. Several molecular structures are generated during cellular injury that can damage membranes, proteins, and nucleic acids. A number of inherent antioxidant compounds are present within the cell to limit the damage. Cellular injury due to reactive oxygen species occurs when these normal defense mechanisms are overwhelmed. free radicals, i.e. they are chemical compounds with a single unpaired electron; they are highly reactive and interact with adjacent molecules, releasing energy but also potentially altering the molecules. free radicals interact with lipids in cell membranes (peroxidation), cellular proteins, and DNA, leading to breaks in its continuity. The mechanism of free radical damage includes ROS-induced peroxidation of polyunsaturated fatty acids in the cell membrane bilayer, which causes a chain reaction of lipid peroxidation, thus damaging the cellular membrane and causing further oxidation of membrane lipids and proteins. The imbalance between free radical generation and scavenging that occurs in injury is referred to as oxidative stress. Free radicals can be generated by a variety of processes and are thought to be important in so-called reperfusion injury (this occurs after restoration of blood flow in ischaemic tissues), chemical injury, and radiation damage **Mechanism of ROS** Mitochondria are the main source of endogenous reactive oxygen species (ROS) produced at cell level. The overproduction of free radicals can damage macromolecules such as nucleic acids, proteins and lipids. This leads to tissue damage in various chronic and degenerative diseases Free radical-induced lipid peroxidation further damages their structures. Activation of proteases can also disrupt the cytoskeleton and, as this is anchored to the plasma membrane, there is further damage to the overall structure of the cell. Disruption of lysosomal membranes leads to escalation of the cell injury. These organelles are packets of highly reactive enzymes including DNAases and proteases; release of these enzymes into the cytosol almost inevitably leads to the demise of the cell. C:\\Users\\User\\Desktop\\22.jpg.  **Important enzymes responsible for respiratory burst** **1)** **NADPH** **oxidase** present in lysosomal membrane now fused with phagosome product NADPH O~2~ + NADPH 2O~2~ + NADPH + H oxidase A- NADP required form HMP shunt ( produces more NADPH ) B- O~2~^-^ spontaneous becomes H~2~O~2~ + O These oxygen metabolites are the principles killers of becteria **2**-**H~2~O~2~** **myeloperoxidase** ( myeloperoxidase dependent killing ) The quantities of H~2~O~2~ produce by phagolysosome are insufficient to induce effective killing of bacteria The auzorophilic granules of neutrophils contain MPO which in the presence a halid such as CL or I or Br convert MPO MPO H~2~O~2~ to HOCL H~2~O~2~ + CL HOCL CL HOCL Is a powerful oxidant & antimicrobial agent **3**- **Nitric** **oxide** **synthesase** ( NOS ) that produce NO & production of pyroxinitrate via O~2~^-^ The **Haber--Weiss reaction** generates OH ([hydroxyl radicals](https://en.wikipedia.org/wiki/Hydroxyl_radical)) from H~2~O~2~ ([hydrogen peroxide](https://en.wikipedia.org/wiki/Hydrogen_peroxide)) and [superoxide](https://en.wikipedia.org/wiki/Superoxide) ( O~2~^−^) [catalyzed](https://en.wikipedia.org/wiki/Catalysis) by [iron](https://en.wikipedia.org/wiki/Iron) ions. It was first proposed by [Fritz Haber](https://en.wikipedia.org/wiki/Fritz_Haber) and his student [Joseph Joshua Weiss](https://en.wikipedia.org/wiki/Joseph_Joshua_Weiss) in 1932.[^\[1\]^](https://en.wikipedia.org/wiki/Haber%E2%80%93Weiss_reaction#cite_note-Haber_Weiss_1932-1) Haber--Weiss reaction was a source of radicals responsible for cellular [oxidative stress](https://en.wikipedia.org/wiki/Oxidative_stress). The reaction is [kinetically](https://en.wikipedia.org/wiki/Chemical_kinetics) slow, but is [catalyzed](https://en.wikipedia.org/wiki/Catalysis) by dissolved [iron](https://en.wikipedia.org/wiki/Iron) ions. The first step of the [catalytic cycle](https://en.wikipedia.org/wiki/Catalytic_cycle) involves the reduction of the [ferric](https://en.wikipedia.org/wiki/Ferric) (Fe^3+^) ion into the [ferrous](https://en.wikipedia.org/wiki/Ferrous) (Fe^2+^) ion: Fe^3+^ + O~2~^−^ → Fe^2+^ + O~2~ The second step is the [Fenton reaction](https://en.wikipedia.org/wiki/Fenton%27s_reagent): Fe^2+^ + H~2~O~2~ → Fe^3+^ + OH^−^ + OH Net reaction: O~2~^−^ + H~2~O~2~ → OH + OH^−^ + O~2~