Uncouplers -1

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Uncouplers -1

  1. 1. Inhibitors and Uncouplers Any compound that Table 1. Inhibitors of Respiration and Oxidative Phosphorylation compound that Any Site-Specific Target Complex Carbon monoxide Cyanide Sodium Azide Rotenone Antimycin A Amytal IV IV IV I III I Phosphorylation Oligomycin Fo Uncouplers 2,4-Dinitrophenol (DNP) Trifluorocarbonylcyanide Phenylhydrazone (FCCP) Proton gradient Proton gradient stops electron stops electron transport will stop transport will stop respiration…this respiration…this means you stop means you stop breathing breathing Electron transport can Electron transport can be stopped by be stopped by inhibiting ATP inhibiting ATP synthesis synthesis An uncoupler breaks An uncoupler breaks the connection between the connection between ATP synthesis and ATP synthesis and electron transport electron transport
  2. 2. What is an Uncoupler? Uncouplers break the connection between electron transport and phosphorylation Electron transport is a motor Phosphorylation is the transmission Uncouplers let you put the car in NEUTRAL
  3. 3. Table 2. Action of Inhibitors on Respiration and Phosphorylation Agent or Condition 1. Inhibit electron transport………. 2. Inhibit phosphorylation……….. 3. Increase proton gradient………. 4. Decrease proton gradient……… 5. Add DNP……………………… 6. Add Oligomycin………………. 7. Add Oligomycin + DNP……… O2 uptake ATP synthesis
  4. 4. 2,4-dinitrophenol – a proton ionophore OH OH O NO2 NO2 NO2 H+ NO2 Matrix NO2 O NO2 H+ NO2 NO2 Inner Membrane Text p519 Text p519
  5. 5. Brown Adipose Tissue Uncoupling a proton gradient from FOF1 ATPase Produces Heat! Thermogenin
  6. 6. Staying Alive Energy Wise • • • • • • • • • We need 2000 Cal/day or 8,360 kJ of energy per day Each ATP gives 30.5 kJ/mole of energy on hydrolysis We need 246 moles of ATP Body has less than 0.1 moles of ATP at any one time We need to make 245.9 moles of ATP Each mole of glucose yields 38 ATPs or 1160 kJ We need 7.2 moles of glucose (1.3 kg or 2.86 pounds) Each mole of stearic acid yields 147 ATPs or 4,484 kJ We need 1.86 moles of stearic acid (0.48 kg or 1.0 pound of fat)
  7. 7. Control of Oxidative phosphorylation What makes us breathe faster? How does ATP synthesis in the mitochondria adjust to the needs of the cell?
  8. 8. WHAT IS THE ATP MASS ACTION RATIO? [ATP] [ADP][Pi] = ATP mass action ratio High: Energy sufficient, Signifies high ATP Low: Energy debt, Signifies high ADP or low ATP HIGH Mass Action Ratio: Oxidized cytochrome C [C3+] is favored Cytochrome oxidase is low because of low C2+ O2 uptake low LOW Mass Action Ratio: Reduced cytochrome C [C2+] is favored Cytochrome oxidase stimulated because of high C2+ Oxygen uptake high
  9. 9. Control of Oxidative Phosphorylation Control of Oxidative Phosphorylation Equilibrium Equilibrium ½NADH + Cyt c (Fe3+) + ADP + Pi ½ NAD+ + Cyt c (Fe2+) + ATP Keq = [NAD+] ½ [NADH] [c2+] [c3+] ∆Go’= 0 ATP [ADP][Pi] [ATP] can control its own production Cytochrome c oxidase step is irreversible and is controlled by reduced cytochrome c (c2+) Because of equilibrium, concentration of c2+ depends on [NADH]/[NAD+] and [ATP]/[ADP][Pi]
  10. 10. Control of Cytochrome Oxidase (Cox) [c2+] = 3+ [c ] NADH ATP mass action ratio ATP mass action ratio [NADH] ½ [ADP][Pi] Keq [ATP] [NAD+] Mass Action ration NADH [c2+]/[c3+] ADP [c2+]/[c3+] ATP [c2+]/[c3+] equilibrium Stimulates Cox equilibrium Stimulates Cox equilibrium Stimulates Cox equilibrium Suppresses Cox Cytochrome oxidase controls the rate of O22 uptake which Cytochrome oxidase controls the rate of O uptake which means this enzyme determines how rapidly we breathe. means this enzyme determines how rapidly we breathe.
  11. 11. Oxygen Radicals Partially reduced oxygen species Molecular Oxygen .. ..O O2 O2 .. ..O .. :: O. . Octet Rule .. :: O. . Unpaired electron Unpaired electron = O2 Superoxide Anion
  12. 12. What is a Free Radical ? Any chemical species with one of more unpaired electrons……. Highly Reactive Powerful Oxidant Short half life (nanoseconds) Can exist freely in the environment
  13. 13. EXAMPLES OF FREE RADICALS H. Hydrogen atom O2 . Superoxide (oxygen centered) OH . Hydroxyl radical (most reactive) . Nitric Oxide NO
  14. 14. PRO-OXIDANTS Fe2+ + H2O2 Ascorbic acid + Fe2+ Paraquat Agent Orange Ozone (Generates Free Radicals) Generates hydroxyl radical Generates hydroxyl radical Generates superoxide radical Generates superoxide radical Generates hydroxyl radical
  15. 15. WHAT ARE ANTIOXIDANTS? WHAT ARE ANTIOXIDANTS? ENZYMES Superoxide dismutase Catalase Peroxidases O2H2O2 R-OOH VITAMINS Vitamin E (tocopherols) Beta Carotene (pro-vitamin A) Vitamin C
  16. 16. Quiz 1 4 Questions 5 Points
  17. 17. 1. Other than Fructose-6-PO4 and Fructose-1,6 bisPO4, name another phophate ester of fructose. Fructose 1-PO4 or Fructose 2,6-bisPO4 2. Other than glycerate-1,3 bisPO4, name another high energy intermediate derived from glucose in glycolysis. PEP 3. Name a compound in the Krebs cycle, which when oxidized to CO2 and H2O gives rise to 30 ATPs Succinyl-CoA 4. Name 2 pentoses that are found in the pentose phosphate pathway. Ribose-5-PO4 Ribulose-5-PO4 Xylulose-5-PO4

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