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Free radicals

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A free radical is a molecule or molecular fragment that contains one or more unpaired electrons in its outermost orbital.
Free radical is generally represented by superscript dot.

Publié dans : Santé & Médecine
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Free radicals

  1. 1. Tapeshwar Yadav (Lecturer) BMLT, DNHE, M.Sc. Medical Biochemistry FREE RADICALS
  2. 2. FREE RADICALS  DEFINITION : A free radical is a molecule or molecular fragment that contains one or more unpaired electrons in its outermost orbital. Free radical is generally represented by superscript dot.
  3. 3. HOW DO THEY GENERATE?  Oxygen atom has two parallel spin electrons in its outermost orbital.  For a bond to occur the other molecule should also have two opposite spin electrons in its outer orbital , so here Oxygen accepts only one electron which is opposite in its spin and hence the other electron is unpaired thus forming free radical and it wanders in search of its compatibility.  Free radicals that are formed by the oxidation reactions are termed as Reactive Oxygen Species.
  4. 4. CHARACTERISTICS OF FREE RADICAL Characteristics of Free radical :  It is highly reactive  Short life span  Causes Damage to various Tissues by generation of new reactive oxygen species by chain reaction.
  5. 5. EXAMPLES OF FREE RADICALS EXAMPLE S OF FREE RADICALS :  Superoxide anion  Singlet oxygen  Hydrogen peroxyl radical  Hydroxyl radical  Hydrogen peroxide  Nitric Oxide  PeroxyNitrite  Lipid peroxide radical.  Hypochlorous acid Out of these H2O2 and Singlet oxygen are not free radicals but due to extreme reactivity they are included in Reactive oxygen Species.
  6. 6. HOW DO THEY GENERATE? Superoxide anion H2O2 Nitric Oxide Xanthine oxidase Xanthine oxidase NO synthase Aldehyde oxidase Aldehyde oxidase NADPH Oxidase Cyt P450 External Sources : Cigarette smoke Inhalation of smoke Ionising radiations Light of appropriate wavelengths cause photolysis of oxygen
  7. 7. WHAT DO THEY DO?  They are constantly produced during the normal oxidation of foodstuffs.  As they are electron deficient, they wander in the cell for their stability and effect the bio membranes.  These oxidants can 1) oxidize SH group containing membrane protein in the cells 2) oxidizes Methionine to Sulphoxide 3) oxidizes Membrane Lipids and it reduces the optimum fluidity of the membrane causing membranopathy. 4) and it causes damage to DNA They
  8. 8. Oxidative Stress  Oxidative stress represents an imbalance between the production of reactive oxygen species or decrease in the antioxidant status in the body. Disturbances in the normal redox state of tissues can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA.
  9. 9. STAGES OF LIPID PEROXIDATION THREE STAGES OF LIPID PEROXIDATION : INITIATION : This is caused by O2 and OH free radical. These affect the PUFA’S at the methylene bridge and convert it into a free FA radical by taking off a Hydrogen atom. RH + OH’ R’ + H2O ROOH’ ROO + H+ PROPAGATION: The free FA radical binds with O2 to give FA peroxy radical and then changes to FA peroxide radical by accepting Hydrogen from Methylene group and these reactions takes place by generating new radicals until a Termination process occurs. R’ + O2 ROO’ ROO’ + RH ROOH + R’
  10. 10. Continuation…. TERMINATION : When two Radicals combine together the product formed is a stabilised one ROO’+ ROO’ RO-OH + O2 R’ + R’ R—R ROO’ + R’ RO--OR
  11. 11. Continuation….  Diradicals Diradicals are molecules containing two radical centers.Atmospheric oxygen and triplet oxygen naturally exists as a diradical in their ground state. The high reactivity of atmospheric oxygen is due to its diradical state. Interestingly, non-radical states of dioxygen are actually less stable. The diradical state of oxygen shows paramagnetic character towards an external magnet.
  12. 12. DIAGNOSTICS Free radical diagnostic techniques include: 1)Electron spin resonance This is alternately referred to as "electron paramagnetic resonance" (EPR) spectroscopy. In ESR, the energy levels are produced by the interaction of the magnetic moment of an unpaired electron in a molecule ion with an applied magnetic field. 2)Nuclear magnetic resonance using a phenomenon called CIDNP (chemically induced dynamic nuclear polarization)
  13. 13. Continuation…. 3)Chemical labelling Chemical labelling by quenching with free radicals, e.g. with nitric oxide (NO) or DPPH (2,2-diphenyl-1- picrylhydrazyl), followed by spectroscopic methods like X-ray photoelectron spectroscopy (XPS) or absorption spectroscopy, respectively. 4)Use of free radical markers Stable, specific or non-specific derivates of physiological substances can be measured e.g by lipid peroxidation products (isoprostanes, TBARS), by amino acid oxidation products (meta-tyrosine, ortho-tyrosine, hydroxy-Leu, dityrosine etc.) and by peptide oxidation
  14. 14. Continuation…. 5)Indirect method Measurement of the decrease in the amount of antioxidants (e.g. TAS, reduced glutathione - GSH) 6)Trapping agents Using a chemical species that reacts with free radicals to form a stable product that can then be readily measured.
  15. 15. THANK YOU