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2013-06-18 03:55:48
Bioenergetics oxidative phosphorylation

Ch.6 Bioenergetics and oxidative phosphorylation
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  1. Thermodynamics
    1st Law
    • ΔE=q-w
    • The energy is constant
    • E=change in internal energy
    • q=heat absorbed by system
    • w=work done by system
    • ex. ice water transition
  2. Thermodynamics
    2nd Law
    • Entropy increases
    • ΔG=ΔH-TΔS
    • G=change in free energy
    • H=change in enthalpy
    • S=change in entropy
    • ex: rubber band
  3. Energy change
    rxn does not serve as an energy source in cells

    ADP is indirectly used as energy source.
  4. Adenylate kinase rxn
  5. Creatine Kinase
    Creatine phosphate + ATP=creatine +ADP

    • Meat=creatine
    • If intake more creatine=problem with kidney filtration and votiming
  6. Creatine phosphate
    Reservoir of high energy phosphate in muscle cells
  7. Citric acid cycle produces
    Nadh + H and FADH2
  8. Electron transport system responsible for
    re-oxidation of nadh+h and FADH by o2
  9. oxidative phosphorylation process
    • ATP synthesized as electrons pass from NADH+H and FADH2 to O2
    • major site for ATP production in tissue
    • ADP level controls the rate
    • 02 depends on availability of ADP
  10. Cytochromes
    • Heme proteins
    • electron carriers in electron transport system
    • iron in the heme in either state (Fe3 & Fe2)
    • absorb light
  11. Chemiosmotic Theory (Proton-motive force)
    • In electron transport H goes out of mitochondria, sets up a gradient with H+ greater conc outside the inner membrane
    • The force increases synthesis of ATP by ATP synthase
  12. Complex 1
    NADH dehydrogenase
  13. complex II
    Succinate dehydrogenase
  14. complex III
    cytochrome reductase
  15. complex IV
    cytochrome oxidase
  16. complex V
    ATP synthase

    • H ions pass back into the matrix
    • e pair pass from FADH to O2 generates 2.5atp
    • e pair bypass complex I from FADH to O2 makes 1.5ATP
  17. slide 22: Inhibitor of atp synthase
    • 1. amobarbital (amytal, barbituate), and rotenone: blocks e transport, in Complex I
    • 2. Antimycin (antibiotic): blocks e transport, in complex III
    • 3. Oligomycin: blacks atp synthase in complex V
  18. Chemiosmotic coupling
    ATP made from ADP+P, by a proton gradient across the inner mitochondrial membrane
  19. slide 16 Respiratory complexes
    • Proton pumps
    • electron passes through complexes I,III,IV
    • H+ ions are "pumped" across inner mitochon-memb into intermembrane space.
  20. 1. mitochondrial matrix
    H+ conc. in intermembrane space increases
  21. 2. Proton motive force as a result of
    • A. difference of PH
    • B. Difference of electrical potential between intermem-space and mito-matrix.
  22. atp calculation
    38 atp generated from glucose to CO2

    • A. 1nadh-> 3atp
    • B. 1fadh-> 2atp
  23. respiratory control
    ADP controls the rate of oxidative phospho.
  24. LOW adp (low ATP)
    • decrease flow of e
    • decrease 02 consumption
  25. HIGH adp (high ATP)
    • increase flow of e
    • increase 02 consumption
  26. pills taken for high cholesterol
    • CoQ10
    • Increased chol.=increased CoQ10 (statin) given= increased muscle pain.
  27. Inhibitors
    • inhibit electron transport
    • inhibit oxidative phospho. if coupled to electron transport
    • A. carbon monoxide
    • B. cyanide
    • They are poisons because they compete with O2 for binding to cytochrome oxidase of the ETC.
  28. cyanide gas production
    • from bonding of C,H, and N during burning of synthetic materials. 
    • in all cars, garage, dumpster, house fires.
  29. Hydrogen cyanide
    prevents body from using O2 no matter how high of oxygen you get.
  30. cyanide exposure, s&s
    • fast acting
    • ingested or absorbed
    • burning sensation
    • headache, confusion
    • hypertension
    • seizures
    • pulmonary edema
    • similar to CO2

  31. ***Cyanide (Lilly) kit has
    • amyl nitrite (inhaler)
    • sodium nitrite(IV)
    • sodium thiosulfate (IV)
    • nitrites: convert hemoglobin to methemoglobin
    • Methemoglobin: removes cyanide from cytochrome oxidase from cell allowing cell resp.
    • Thiosulfate: bonds to freed cyanide making thiocyanate then renally excreted
  32. side effects of lilly kit
    • Nitrites: cause hypotension
    • meth: prevents 02 transport
    • bad following smoke inhalation
  33. ***Cyanokit: low side effects
    Contains: Hydroxocabalmin binds with
    • ****cyanide to create B12 (cyanocobalamin)
    • non toxic - excreted by kidneys

    • 2vials of hydrocab 2.5gm
    • 100cc NS
    • 5 grams infused over 15min
    • Candidates: hypotension, lactic acidosis >10, high venous 02 SKIP
  34. uncoupling agents
    • cause a "proton leak" allowing prot to re-enter mito. matrix without capturing En- ATP
    • in other words: they carry H+ across mit. mem. without going through comlex 5. this short circuits proton gradient and uncoup e flow.
    • E that would be used to make ATP is dissipated as heat
  35. ***in class notes***
    • Uncouple atp synthase from ETC
    • lower proton gradient
    • atp synthase (complex 5) cant make ATP
    • lack of energy, inc. ETC, which Inc. 02
    • the resulting energy is lost as heat
    • uncoup: will lower atp prod. and slow down the ETC
  36. Uncoulpler: dinitrophenol
    • DNP collapses the H gradient across the membrane
    • found in brown fat
    • a med that was used for weight loss, and caused blindess (retina has oxidative metabolism)
  37. uncoupler protein: thermogenin
    • mito. of brown fat
    • allows proton pass through inner membrane without synth. ATP
    • energy given off as heat to maintain body temp (in newborns)
  38. Uncoupler: Thyroxin
    hormone stimulates heat production
  39. Mito. transport system
    • ATP-ADP translocase in inner mitoch. memb. carries coupled exchange of atp & adp
    • outer membrane is permeable, Inner memb. is not
    • shuttle transport e from cytosolic nadh into mito.
    • shuttle permits regeneration of cytosolic NAD which is necessary for glycolysis to continue
  40. slide 46: Glycerol phosphate
    • shuttle uses cytosolic NADH to reduce dihydroxyactone  phosph. to glyc 3 phosph.
    • transfers e to fAD in inner mito. memb.
    • 2cytosolic nadh = 4atp
    • location: muscle & brain
    • feature: unidirectional and costs 1 ATP
    • 2 nadh formed: 2x1.5= 3atp
  41. Malate aspartate
    • shuttle uses cytosolic nadh to reduce oxaloacetate to malate
    • enters mito. by an antiporter
    • 2nadh = 6 atp
    • location: liver, kidney, heart
    • feature: bidirectional, cost no atp.
    • 2x2.5=5atp
  42. pyruvate dehydrogenase atp yield
    2 nadh formed = 5 atp
  43. atp yield from glucose oxidation
    • Citric acid cycle
    • 2 turns of cycle required
    • total: 30 or 32ATP depending on which shuttle
  44. Mito. diseases
    • affect e transport and atp synthesis
    • mutations in mit. DNA (mtDNA)
    • mito. in the zygote come from ovum; they have maternal inheritance
    • mothers transmit disease to children
    • males dont transmit because tail of sperm (contains the mito.) falls off during fertilization
    • mtDNA proteins are associated with e transport and atp synthesis
    • tissues with high o2 demand are most effected by mito. dysfunction.
  45. Leber's hereditary optic neuropathy
    • loss of vision and blindness due to degeneration of optic nerve
    • defect in nadh dehydrogenase (complex I)
  46. Kearns-sayre syndrome
    • degeneration of retinal pigments
    • paralysis of ocular muscle (ophthalmoplegia)
    • ragged red fibers
    • irregular contour
    • abnormal mito. that stain red
  47. MELAS syndrome
    • mito. encephalomyopathy
    • lactic acidosis
    • stroke symptoms
  48. 6.1 pt. with large mitochondria with packed cristae. high basal ATPase activity. oxidation and phosphorylation uncoupled
    pt has hypermetabolism and high core temp.
  49. 6.2 why and how malate aspartate shuttle moves nadh reducing cytosol to mito. matrix.
    • there is no transport for nadh in inner mito. memb.
    • nadh can be oxized to nad by cytoplasmic isozyme malate dehyd. as oxaloacetate is reduced to malate
    • malate is transported across inner membrane, mito. isozyme of malate dehydrogenase oxidizes to oxaloacetate as mito. nad is reduced to nadH
    • The nadh can be oxidized by complex I of ETC generating 3 atp through the coupled process of resp. and oxidative phosphor.
  50. 6.3 CO binds/inhibits complex IV of ETC. what effect should respiratory inhibitor have on oxidative phosphor.
    inhibition of ETC by resp. inhibitors such as CO result in inability to maintain proton gradient

    oxidative phosphor. is therefor inhibited