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18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
18.oxidative phosphorylation
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18.oxidative phosphorylation

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  • 1. OXIDATIVE PHOSPHORYLATION
  • 2. DEFINITION  Oxidative phosphorylation is the name given to the synthesis of ATP from ADP ( phosphorylation), that occurs when NADH and FADH2 are oxidized by electron transport throughout the respiratory chain (hence called oxidative)  Mitochondria are the site of oxidative phosphorylation in eukaryotes ,
  • 3. There is two ways to synthesize ATP Oxidative phosphorylation : the phosphorylation of ADP to ATP coupled to electron transfer Substrate level phosphorylation : direct transfer the phosphate from chemical intermediate (also called substrate ) to ADP or GDP forming ATP or GTP , independent of electron transfer chain
  • 4. Example of Substrate level phosphorylation 1) 1,3-bisphosphoglycerate Glycolysis ADP Phosphoglycerate kinase ATP 3-phosphoglycerate
  • 5. 2) Phosphoenolpyruvate Glycolysis ADP Pyruvate kinase ATP Pyruvate 3) succinyl CoA TCA cycle GDP succinyl CoA synthetase GTP succinate
  • 6. CHEMIOSMOTIC HYPOTHESIS  Is the mechanism of oxidative phosphorylation ,  proposed by Peter Mitchell in 1961
  • 7. The chemiosmotic hypothesis : it proposed that energy liberated by electron transport is used to create a proton gradient across the mitochondrial inner membrane and it is this proton gradient is used to drive ATP synthesis Thus the proton gradient couples electron transport and ATP synthesis
  • 8. ATP SYNTHASE  Also called complex Ⅴ  It is the enzyme that actually synthesize ATP  It located in the inner mitochondrial membrane  It utilizes energy from the proton gradient to promote phosphorylation of ADP forming ATP
  • 9. THE STRUCTURE OF ATP SYNTHASE  The ATP synthase can be seen as spherical projections from the inner membrane .  Is composed of two major components part , F1 unit or called F1 ATPase : is the spheres of the ATP synthase and point outward F0 unit : spans the inner mitochondria membrane So the ATP synthase is also called F0F1 ATPase  The stalk between F0 and F1 contains several additional polypeptide
  • 10. The structure of ATP synthase Matrix F1 unit F0 unit Proton channel Intermembran space
  • 11. The function of ATP synthase F1 unit : contains 5 polypeptides in the form α3β3γδε. only F1 components can hydrolyze ATP, have ATPase activity , so also called ATPase , F1 with F0 together can synthesize ATP F0 unit: made of abc polypeptides, is proton channel, can be seen as the proton transport , The complete complex harnesses the energy released by electron transport to drive ATP synthesis
  • 12. In summary : the oxidative phosphorylation process is as follow Electron transport down the respiratory chain from NADH or FADH2 Complex Ⅰ ,Ⅲ ,Ⅳ Cause protons be pumped out of the mitochondrial matrix into the intermembrane space
  • 13. The pumping out of H+ generates a higher concentration of H+ and an electrical potential , thus an electrochemical proton gradient is formed . The H+ flow back into the mitochondrial matrix through ATP synthase and the electrochemical proton gradient drives ATP synthesis
  • 14. ELECTROCHEMICAL PROTON GRADIENT Is the sum of chemical gradient : a higher concentration of H+ ions form the chemical gradient of H+ outer : high concentration H+ inner : low concentration H+  Electrical potential : electrical charge potential across the inner mitochondrial membrane outer: positive charge inner: negative charge
  • 15. The chemiosmotic hypothesis : matrix H2O Low H+ Negitive charge ADP + Pi ATP e- - - - - O2 ++++ H+ High H+ Positive charge H+
  • 16. The chemiosmotic hypothesis : Intermembrane space H+ + Cyt c H+ + + + + + H+ + + + Q - Ⅰ - Ⅱ F0 - Ⅲ - - - Fumarate NADH+H+ NAD+ + Succinate 1/2O2+2H+ Ⅳ - - - H2O F1 mattix ADP+Pi ATP H+
  • 17. GENERATE ATP SUMS  3 ATP are synthesized per NADH oxidized through the NADH respiratory chain  2 ATP are synthesized per FADH2 oxidized through the FADH2 respiratory chain
  • 18. WHY ATP SYNTHESIZE FROM FADH2 RESPIRATORY CHAIN IS LESS THAN NADH RESPIRATORY CHAIN ?  NADH Ⅰ ,Ⅲ ,Ⅳ  respiratory have 3 H+ pump, complex FADH2 respiratory only have 2 H+ pump, complex Ⅲ ,Ⅳ  So the ATP made from FADH2 is less than from NADH
  • 19. The process of biological oxidation
  • 20. COUPLING OF ELECTRON TRANSPORT AND PHOSPHORYLATION
  • 21. Electron transport is normally tightly coupled to ATP synthesis  electrons do not flow through the electron transport chain to oxygen unless ADP is simultaneously phosphorylated to ATP  Also , ATP is not synthesized unless electron transport is occurring to provide the proton gradient
  • 22.  Thus we can know that oxidative phosphorylation needs NADH or FADH2 , oxygen , ADP , and inorganic phosphate
  • 23. COUPLING SITE OF ELECTRON TRANSPORT AND PHOSPHORYLATION  complex Ⅰ ,Ⅲ ,Ⅳ How to know this ?  P:O ratio: in oxidative phophorylation the P:O ratio is the number of ATP formed per oxygen atom is consumed
  • 24. NADH respiratory chain : P:O ratio=3 forming 3 ATPs per oxygen atom consumed , NADH respiratory chain have 3 coupling site FADH2 respiratory chain : P:O ratio=2 forming 2 ATPs per oxygen atom consumed , FADH2 respiratory chain have 2 coupling site
  • 25. UNCOUPLERS
  • 26. WHAT IS UNCOUPLERS?  Some chemicals act as uncoupling agents, that is, when added to cell, they stop ATP synthesis but electron transport still continues and so oxygen is still consumed The chemicals for example : • 2,4-dinitrophenol (DNP) • uncoupling protein
  • 27. DNP  DNP  are lipid-soluble small molecule that can bind H+ ion and transport the H+ across the mitochondria membrane ,  So it is H+ ionophores
  • 28. HOW DNP UNCOUPLING  ? electron transport occurs and pump out H+ ions across the inner mitochondrial membrane to build the H+ gradient .  But DNP in the same membrane carriers the H+ ions back into the mitochondrion , preventing formation of a proton gradient.  Since no proton gradient forms, so no ATP can be made by oxidative phosphorylation  the energy derived from electron transport is released as heat
  • 29. UNCOUPLING PROTEIN  There  is brown adipose tissue in the body , this tissue is rich in mitochondria, the inner mitochondrial membranes of which contains a protein called uncoupling protein or thermogenin
  • 30. HOW UNCOUPLING PROTEIN WORK ?  Uncoupling protein can be seen as a H+ passageway , allows H+ to flow back into mitochondria without having to enter the ATP synthase ,  thus preventing formation of a proton gradient , so uncouples electron transport and oxidative phosphorylation ,  And also energy derived from electron transport is released as heat
  • 31. mechanism of uncoupling protein ( brown adipose tissue mitochondrial ) Intermembrane space Heat energy H+ Cyt c Uncoupling protein Q Ⅰ Ⅱ F0 Ⅲ Ⅳ F1 Matrix ADP+Pi ATP H+
  • 32. THERMOGENESIS  The production of heat by uncoupling is called nonshivering thermogenesis .  It is important in certain biological situation ,  For example ,the brown adipose tissue is found in sensitive body areas of some new brown animals (including human ), where the heat production provides protection from cold condition  In addition, thermogenesis by brown adipose tissue plays a important role in maintaining body temperature in hibernating animals
  • 33. RESPIRATORY CONTROL
  • 34. ADP: The actual rate of oxidative phosphorylation is set by the availability of ADP If ADP is added to mitochondrial, the rate of oxygen consumption rises as electrons flow down the chain Then when all the ADP has been phosphorylated to ATP, the rate of oxygen consumption falls This process called respiratory control
  • 35.  this mechanism ensures that electrons flow down the chain only when ATP synthesis is needed. If the level of ATP is high ,ADP is low, no electron transport occurs NADH and FADH2 build up, so does excess citrate then the citric acid cycle and glycolysis are all inhibited
  • 36. OVER ALL ADP high Oxidative phosphorylation rises Oxygen consumption rises ADP low Oxidative phosphorylation falls Oxygen consumption falls
  • 37. ATP
  • 38. Ester bond Adenine NH2 N O HO r P OH O O β P OH ATP N O O α P O CH2 O N N OH OH OH Glycosidic bond Ribose Adenosine triphosphate: ATP
  • 39. Production and application of ATP ATP oxidative Phosphorylation substrate level Phosphorylation ~P ~P ADP Mechnism energy Osmotic energy Chemical energy Electric energy Hot energy
  • 40. RIOXIDATION OF CYTOSOLIC NADH
  • 41.  The inner membrane of mitochondria impermeable to some molecule and ions Permeable to : pyruvate 、 succinate 、 citrate α-ketoglutarate 、 malate 、 Glu ect Impermeable to : H+ 、 NADH 、 NADPH 、 oxaloacetate ect
  • 42.  The inner mitochondrial membrane is impermeable to NADH.  Therefore NADH produced in the cytoplasm during glycolysis go into the mitochondria through the membrane shuttle , then in the mitochondria go into the respiratory chain .  The membrane shuttle is a combination of enzyme reaction that bypass this impermeability barrier
  • 43. WHICH REACTION OF GLYCOLYSIS PRODUCE NADH Glyceraldehyde 3-phosphate NAD+ Glyceraldehyde 3-phosphate Dehydrogenase NADH 1,3-bisphosphoglycerate The reaction take place in the cytosol
  • 44. THERE IS TWO SHUTTLE SYSTEM IN THE MITOCHONDRIAL MEMBRANE • glycerol 3-phosphate shuttle • Malate-asparate shuttle
  • 45. Dihydroxyacetone Phosphate NADH+H+ Glycerol 3-phosphate Dehydrogenase Dihydroxyacetone Phosphate electron chain FADH2 Glycerol 3-phosphate Dehydrogenase FAD NAD+ Glycerol 3-phosphate Cytosol Glycerol 3-phosphate inner Membrane • glycerol 3-phosphate shuttle
  • 46. Dihydroxyacetone Phosphate CH2OH CH2OH NADH+H+ Glycerol 3-phosphate Dehydrogenase NAD+ C=O C=O CH2O- Pi CH2O- Pi Glycerol 3-phosphate Dehydrogenase CH2OH CH2OH CHOH FADH2 FAD CHOH CH2O- Pi Glecerol 3-phosphate electron chain CH2O- Pi Intermembrane Space outer Membrane • glycerol 3-phosphate shuttle matrix inner Membrane
  • 47. Dihydroxyacetone phosphate in the cytosol is reduced to glycerol -3-phosphate , and NADH reoxidized to NAD+, by cytosolic glycerol 3- phosphate dehydrogenase The glycerol -3-phosphate diffuse across the inner mitochondrial membrane
  • 48. In the inner membrane the glycerol 3-phosphate is converted back to dihydroxyacetone phosphate by mitochondrial glycerol 3-phosphate dehydrogenase the mitochondrial glycerol 3-phosphate dehydrogenase does not use NAD+ but instead uses FAD. The FADH2 is then reoxidized by FADH2 respiratory chain.So 2 ATPs are synthesized ) The dihydroxyacetone phosphate then diffuse back to the cytosol .
  • 49. Note :  The shuttle does not allow cytoplasm NADH to enter the mitochondrion,  but transports the two electrons from NADH into the mitochondria  and feed the electron into the FADH2 electron transport chain . So synthesize 3ATPs 
  • 50. Cytosol inner memebrane Malate NAD+ malate dehydrogenase malate α-ketoglutarate carrier malate NAD+ malate dehydrogenase NADH +H+ NADH +H+ Oxaloacetate Oxaloacetate α-ketoglutarate Aspartate Aminotransferase α-ketoglutarate Aspartate Aminotransferase glutamate Aspartate glutamate – aspartate carrier glutamate Aspartate
  • 51. glutamate – aspartate carrier - + H 3N - - - OOC-CH2-C-COO OOC-CH2-C-COO H H O H3N -OOC-CH2-C-COO- oxaloacetate - NADH +H+ + - OOC-CH2-CH2-C-COO H3N - asparate O + - OOC-CH2-CH2-C-COO -OOC-CH2-C-COO- glutamate H H inner memebrane malate dehydrogenase NAD + H 3N aspartate aminotransferase O -OOC-CH2-CH2-C-COO- NADH +H+ O -OOC-CH2-CH2-C-COO- NAD+ + α-ketoglutarate OH OH -OOC-CH2-C-COOH malate intermembrane space -OOC-CH2-C-COO- malate α-ketoglutarate carrier H matrix malate
  • 52. Oxaloacetate in the cytosol is converted to malate by cytosolic malate dehydrogenase. NADH oxidized to NAD+ The malate enters the mitochondrion by amalate-α-ketoglutarate carrier in the inner mitochondrial membrane In the matrix the malate is reoxidized to oxaloacetate , NAD+ form NADH. Then NADH go into the NADH respiratory chain And 3ATPs are synthesized
  • 53.  Oxaloacetate does not easily cross the inner mitochondrial membrane and so is transaminated to form aspartate  And then the aspartate exits from the mitochondrion and is reconverted to oxaloacetate in cytosol , again by transamination
  • 54. Note  this cycle of reactions is to transfer the electrons from NADH in the cytosol to NADH in the mitochondrial matrix ,  The NADH in the mitochondria is then reoxidized by the NADH electron transport chain  So synthesize 3ATPs
  • 55. In summary : Cytosol NADH go into the mitochondria by this two shuttele • glycerol 3-phosphate shuttle in the mitochondria go into the FADH2 respiratory chain . so produce 2 ATPs Malate-asparate shuttle: in the mitochondria go into the NADH respiratory chain. so produce 3ATPs
  • 56. Practice exercises 1. Description Composition of respiratory chain complex ComplexⅠ : NADH dehydrogenase or called NADH-CoQ reductase complex Ⅱ : Succinate-coenzyme Q reductase complex Ⅲ : Cytochrome bc1 complex or called cytochrome reductase complex Ⅳ : Cytochrome oxidase
  • 57. 2. Write down the two respiratory chain NADH respiratory chain FMN (Fe-S) NADH complexⅠ CoQ Cytb 、 Fe-S 、 Cytc1 Complex Ⅲ succinate FAD (Fe-S) complexⅡ FADH2 respiratory chain Cyt c Cytaa 3 Cu CuB Complex Ⅳ O2
  • 58. 3. Filling the blank  There is two respiratory chain in the body : that is ( ) and ( ) NADH respiratory chain FADH2 respiratory chain
  • 59. 4. Explain : electron transport chain Electron transport chain: The electrons are transferred from NADH to oxygen along a chain of electron carriers collectively called electron transport chain , also called respiratory chain.
  • 60. 5. Choice the sequence of Cytochoreme in respiratory chain  A. c c1 b aa3 O2  B . c1 c b aa3 O2  C. b c1 c aa3 O2  D. b c c1 aa3 O2  E. c b aa3 O2 c1
  • 61. 6. ROTENONE INHIBIT ELECTRON TRANSPORT AT ( )  A. NADH dehydrogenase  B. cytochrome bc1 complex  C. cytochrome oxidase  D. Succinate –Q dehydrogenase  E. cytochrome c (A )
  • 62. 7. ANTIMYCIN A INHIBIT ELECTRON TRANSPORT AT ( ) • • • • • A. NADH dehydrogenase B. cytochrome bc1 complex C. cytochrome oxidase D. Succinate –Q dehydrogenase E. cytochrome c (B )
  • 63. 8. CARBON MONOXIDE (CO) INHIBIT ELECTRON TRANSPORT AT ( ) • • • • • A. NADH dehydrogenase B. cytochrome bc1 complex C. cytochrome oxidase D. Succinate –Q dehydrogenase E. cytochrome c (C )
  • 64. 9. COUPLING SITE OF ELECTRON TRANSPORT AND PHOSPHORYLATION ARE( ) A. complex Ⅰ B. complex Ⅱ C. complex Ⅲ D. complex Ⅳ E. complex Ⅴ ( A,C,D )
  • 65. 10. THE TWO WAYS TO SYNTHESIZE ATP ARE ( ) AND ( ) -Oxidative phosphorylation -substrate level phosphorylation
  • 66. 11. THE MECHANISM OF OXIDATIVE PHOSPHORYLATION IS ( ) -Chemiosmotic hypothesis
  • 67. 12. THE ENZYME THAT ACTUALLY SYNTHESIS ATP IS ( ), IT IS MADE UP OF ( )UNIT AND ( ) UNIT ATP synthase F0 , F1
  • 68. NADH PRODUCED IN THE CYTOPLASM MUST BE REOXIDIZED VIA A MEMBRANE SHUTTLE . THE TWO SHUTTLE SYSTEM ARE ( ) AND ( ) 13. -glycerol 3-phosphate shuttle -Malate-asparate shuttle
  • 69. 14 . If ADP is high, The Oxidative phosphorylation and Oxygen consumption will ( ) . if ADP is low , The Oxidative phosphorylation and Oxygen consumption will ( ) rises , falls
  • 70. 15 . the chemicals that can uncouple the electron transport with the ATP synthesis are ( ) and ( ) DNP, Uncoupling protein

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