Biochem Lecture 22

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mprosenberg
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243812
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Biochem Lecture 22
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2013-10-30 17:10:53
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Biochem 501
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Biochem Lecture 22
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  1. Pentose Shunt (Pathway, from Glucose-6-phosphate)
    Glucose-6-phosphate --> 6-phospho-gluconate --> Ribose 5-phosphate
  2. Pentose Shunt accomplishes what?
    • Anabolic:
    • -Generates NADPH for biosynthesis
    • Catabolic:
    • -Generates pentose-P for nucleotide
    • -Degrades pentose from diet
  3. Pentose Shunt Balanced Reaction
    3Glucose-6-P+6NADP++3H2O-->6NADPH+6H++3CO2+2 Fructose-6-P+Glyceraldehyde-3-P
  4. Two Phases of Phosphate Shunt
    • Oxidative: NADPH and Ribose-5-P
    • Non-oxidative rearrangements: Fructose-6-P and Glyceraldehyde-3-P
  5. Pentose Shunt Diagram
  6. Pentose Shunt Oxidative Step 1:
    Oxidative

  7. Pentose Shunt Oxidative Reaction 2:
    Oxidative

  8. Pentose Shunt Oxidative Reaction 3
    Oxidative

  9. Pentose Shunt Oxidative Step 4
    Oxidative

  10. Pentose Shunt: Oxidative Overview
  11. Pentose Shunt Non-oxidative Reaction 1
  12. Carbon Rearrangements during Non-oxidative phase of Pentose Shunt
    • Reaction 2: C5+C5 --> C3+C7 (Transketolase)
    • Reaction 3: C7+C3 --> C6+C4 (Transaldolase)
    • Reaction 4: C5+C4 --> C6+C3 (Transketolase)
  13. Pentose Shunt Non-oxidative phase Reaction 2
  14. Group Transferred during Reaction 2 of Non-oxidative phase of Pentose Shunt
    • ....C==O
    •    /
    •   CH2--OH
    • /
  15. Pentose Shunt Non-oxidative phase Reaction 3
  16. Group Transferred in Non-oxidative reaction 3 of Pentose Shunt
    • .............CH2---OH
    •              /
    •             C==O
    •            /
    •    HO--C--H
    •          /
  17. Pentose Shunt Non-oxidative phase Reaction 4
  18. Transferred Group in Non-oxidative Step 4 of Pentose Shunt
    • H2C--OH
    •    /
    •  C==O
    • /
  19. Flux of Metabolites in Pentose Shunt
    • Nucleotide Biosynthesis: Ribose-5-Phosphate
    • NADPH Production: Generation of Fructose-6-phosphate/Glyceraldehyde-3-phosphate

    Energy generation: Generation of Fructose-6-phosphate and Glyceraldehyde-3-phospahte for Glycolysis/TCA
  20. Ribose-5-Phosphate from PP Pathway used in?
    Nucleotide Synthesis
  21. Glyceraldehyde-3-Phosphate/Fructose-6-Phosphate made in PP Pathway used for?
    • NADPH Synthesis through Gluconeogenisis into glucose-6-phosphate to repeat cycle
    • or:
    • Energy generation by going through TCA cycle
  22. Rate Limiting Step of PP Pathway
    Glucose-6-Phosphate Dehydrogenase
  23. What substrate's availability controls PP Pathway?
    NADP+
  24. Reactive Oxygen Species
    • O2 + e- --> O2- (Superoxide)
    • O2 + 2e- + 2H+ --> H2O2 (peroxide)
    • O2 + 3e- + 3H+ --> H2O + .OH (hydroxyl free radical)
    • O2 + 4e- + 4H+ --> 2 H2O
  25. Negative Outcomes of ROS
    • -Mutation in DNA
    • -Denatures Proteins
    • -Mitochondria produce ROS
    • -Mitochondria lack DNA repair
    • -Mitochondria susceptible to mutation
  26. Defenses Against ROS
    • Superoxide Dismutase:
    • Turns 2 superoxides and 2 protons into Peroxide and O2

    • Peroxidase, Catalase:
    • Turns 2 peroxides into 2 waters and O2

    • Glutathione peroxidase:
    • Turns 2GSH + H2O2 --> GSSG +2H20
  27. Role of NADPH/Glutathione in ROS removal
    Glutathione reduces the anti-oxidants to that can neutralize more ROS, then transfers the energy to NADPH so that it is useful

    LOOK INTO
  28. Inherited Glucose-6-P Dehydrogenase Deficiency in Erythrocytes
    • Normal circumstances=no symptoms
    • Confers resistance to malaria (falciparum)
    • Causes oxidative stress towards parasite
    • Malaria drugs create oxidative stress in blood

    • Divicine (in fava beans) produces oxidative stress.
    • Those lacking G-6-P dehy cannot repair, 
    • can lead to hemolytic anemia
  29. Wernicke-Korsakoff Syndrome
    • -Severe hemolytic anemia
    • -Uncoordinated movement, eye movement, amnesia
    • -Common in alcoholics
    •     -Ethanol inhibits thiamine uptake
    • -W-K syndrome results in transketolase that does not bind thiamine well
    • -Thiamine deficiency inhibits PP Pathway, reduces NADPH
  30. ROS in Phagocytosis
    • NADPH + 2O2 --> NADP+ + 2O2- + H+
    • Powerful microbicide

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