1 / 19

Free Radicals: Injury induced by free radicals

O 2. Free Radicals: Injury induced by free radicals. (1) Free radical. Free radical——atoms, molecules or ions with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions.

bsumner
Télécharger la présentation

Free Radicals: Injury induced by free radicals

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. O2 Free Radicals: Injury induced by free radicals

  2. (1) Free radical Free radical——atoms, molecules or ions with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions. • Oxygen free radical • Lipid radical

  3. (2) Oxygen free radical, OFR Types： • the superoxide anion (O2-) • the hydroxyl radical (OH ·) • singlet oxygen (1O2 ) • hydrogen peroxide (H2O2)

  4. (3) Lipid free radicals： The interaction of oxygen free radicals with polyunsaturated fatty acids in the phospholipids of cell membrane leads to the formation of lipid free radicals. Types： • Fatty acid radical (L·) • Lipid peroxide（LOO·） (4) Others: Cl·, CH3·, NO·

  5. (5) Generation and elimination of oxygen free radicals 1) Origin of O·-2： a. Mitochondria b. Oxidation of some chemicals in body. c. Catalysis by enzymes d. Stimulation of cells with toxins

  6. (6) Generation of OFR O2 + e O2  SOD O2+ 2e + 2H+ • H2O2 Cytaa3 O2 + 3 e + 3H+ HO +H2O H2O2 Cytochrome aa3 2 H2O O2 + 4 e + 4H+ SOD, Superoxide dismutase

  7. Haber-Weiss reaction (without Fe3 ) O2－+ H2O2 O2 + OH +OH  SLOW hydroxyl radical; ferrum

  8. Fenton-Haber-Weiss reaction Fe3 O2－+ H2O2 O2 + OH +OH  FAST

  9. Dihydrocoenzyme II (6) Elimination of oxygen free radicals 1）Small MW scavenging agents Cysteine, Vit C, glutathione Vit E、 Vit A

  10. Catalase(CAT) Superoxide dismutase 2）Enzymatic scavenging agents MnSOD CuZnSOD Peroxydase（H2O2）

  11. (7) The mechanisms of increased generation of oxygen free radicals during ischemia-reperfusion

  12. Mn− SOD + O-2 Mn+ − SOD + O2 1) Mitochondria pathway Ca2+entering MT O2+e↑ • O-2↑ · Hypoxia Mn-SOD  Superoxide dismutase

  13. Xanthine oxidase (XO) 10% Xanthine dehydrogenase (XD) 90% Ca+2 2) Xanthine oxidase pathway

  14. ATP comsumption↑ Ischemia: Hypoxanthine↑ (1) Ca2+ overload→ activating protein kinase O2 Reperfusion: xanthine+O·-2+ H2O2 XD XO O2 (2) Restoration of O2 supply O·-2+ H2O2+Uric acid Effect of XO on formation of OFR OH ·

  15. 3) Neutrophil pathway Activating neutrophil C3, LTB4 (Complement C3 Leukotriene B4 ) Hexoseshunt activity↑ cellular respiration↑ NADH oxidase NADH(I) NADPH(II) H+ + O-2·+H2O2  + O2 NADPH oxidase

  16. 4) Catecholamines Methyl transferase Adr vanillylmandelic acid (normal) monoamine oxidase Stress 80% O2 Remove O-2· adrenochrome

  17. (8) Alterations induced by OFR 1) lipid peroxidation • Alteration of membrane lipid • Function inhibition of membrane proteins • Enhance of arachidonic acid metabolism • Blockage of ATP production in mitochondria membrane

  18. 80% induced by OH 2) Injury of chromosome and nuclear acid

  19. Destructive effects of OFR: • Attacking membrane structure such as mitochondria membrane  interfering with energy metabolism • Attacking DNA changing genetic information  cell death • Initiating lipid peroxidation increasing permeability of membrane and inducing destruction of membrane cell death • Destroying proteins decreased enzyme activity  metabolic disorder

More Related