Klappa

Public flashcard deck · 111 cards

10.) Pentose phosphate pathway. Reversible and irreversible reactions of the pathway. Oxidative arm - dehydrogenases reactions, role as a source of NADPH (functions of NADPH!) and ribose-5P. Non-oxidative arm role/importance. Consequences of G6P dehydrogenase deficiency.

Study this deck free Add to my library

  1. Front
    Pentose phosphate pathway (PPP)
    Back
    Also called the hexose monophosphate shunt
  2. Front
    Location of the pentose phosphate pathway
    Back
    Cytosol
  3. Front
    Starting substrate of the pentose phosphate pathway
    Back
    Glucose-6-phosphate
  4. Front
    Two main jobs of the pentose phosphate pathway
    Back
    Making NADPH and making ribose-5-phosphate
  5. Front
    Two parts of the pentose phosphate pathway
    Back
    Oxidative phase and nonoxidative phase
  6. Front
    Oxidative phase of PPP
    Back
    Irreversible phase that produces NADPH, ribulose-5-phosphate, and CO2
  7. Front
    Nonoxidative phase of PPP
    Back
    Reversible phase that interconverts sugars and can produce ribose-5-phosphate or glycolytic intermediates
  8. Front
    Direct ATP use or production by PPP
    Back
    The PPP does not directly use or make ATP
  9. Front
    Tissues where PPP is especially important
    Back
    Liver, adipose tissue, adrenal cortex, gonads, lactating mammary gland, and RBCs
  10. Front
    Why PPP is especially important in certain tissues
    Back
    These tissues have a high need for NADPH
  11. Front
    Main role of glycolysis compared with PPP
    Back
    Glycolysis is mainly for ATP, whereas PPP is mainly for NADPH and pentose sugars
  12. Front
    Main products PPP supplies for biosynthesis
    Back
    NADPH for reducing power and ribose-5-phosphate for nucleotide synthesis
  13. Front
    How PPP is linked to glycolysis
    Back
    Its sugars can be converted into fructose-6-phosphate and glyceraldehyde-3-phosphate
  14. Front
    Overall organization of the oxidative phase
    Back
    Oxidation plus decarboxylation, irreversible, produces 2 NADPH, ribulose-5-phosphate, and CO2
  15. Front
    Overall organization of the nonoxidative phase
    Back
    Sugar interconversions, reversible, converts pentoses into ribose-5-phosphate or glycolytic intermediates
  16. Front
    Number of irreversible reactions in the oxidative portion of PPP
    Back
    Three irreversible reactions
  17. Front
    Step 1 enzyme of the oxidative PPP
    Back
    Glucose-6-phosphate dehydrogenase (G6PD)
  18. Front
    Step 1 reaction of the oxidative PPP
    Back
    Glucose-6-phosphate → 6-phosphogluconolactone
  19. Front
    Cofactor reduced in the G6PD reaction
    Back
    NADP+ is reduced to NADPH
  20. Front
    Importance of G6PD in PPP
    Back
    It is the committed, rate-limiting, and regulated step of the pathway
  21. Front
    High-yield regulatory enzyme of PPP
    Back
    G6PD
  22. Front
    Step 2 enzyme of the oxidative PPP
    Back
    6-Phosphogluconolactone hydrolase
  23. Front
    Step 2 reaction of the oxidative PPP
    Back
    6-Phosphogluconolactone → 6-phosphogluconate
  24. Front
    Type of reaction in step 2 of oxidative PPP
    Back
    Hydrolysis
  25. Front
    NADPH production in step 2 of PPP
    Back
    No NADPH is produced in this step
  26. Front
    Step 3 enzyme of the oxidative PPP
    Back
    6-Phosphogluconate dehydrogenase
  27. Front
    Step 3 reaction of the oxidative PPP
    Back
    6-Phosphogluconate → ribulose-5-phosphate + CO2
  28. Front
    Cofactor reduced in the 6-phosphogluconate dehydrogenase reaction
    Back
    NADP+ is reduced to NADPH
  29. Front
    Type of reaction in step 3 of oxidative PPP
    Back
    Oxidative decarboxylation
  30. Front
    Product of step 3 of oxidative PPP
    Back
    Ribulose-5-phosphate
  31. Front
    Two dehydrogenases in the oxidative arm of PPP
    Back
    G6PD and 6-phosphogluconate dehydrogenase
  32. Front
    Which oxidative PPP reactions generate NADPH
    Back
    The G6PD reaction and the 6-phosphogluconate dehydrogenase reaction
  33. Front
    Net result of the oxidative arm per 1 glucose-6-phosphate
    Back
    2 NADPH, 1 ribulose-5-phosphate, and 1 CO2
  34. Front
    Regulation of the oxidative phase of PPP
    Back
    Regulated mainly at G6PD
  35. Front
    Effect of high NADPH on G6PD
    Back
    NADPH inhibits G6PD
  36. Front
    What ratio inhibits the oxidative PPP
    Back
    High NADPH/NADP+ ratio
  37. Front
    What happens to PPP flux when NADPH is being consumed
    Back
    NADP+ rises, inhibition falls, and pathway flux increases
  38. Front
    Effect of insulin on G6PD expression
    Back
    Insulin upregulates G6PD expression
  39. Front
    State in which insulin increases PPP activity
    Back
    Absorptive or fed state
  40. Front
    High-yield regulation summary for PPP
    Back
    High NADPH turns PPP off, whereas low NADPH or high NADP+ turns PPP on
  41. Front
    Immediate product of the oxidative phase relevant to pentose metabolism
    Back
    Ribulose-5-phosphate
  42. Front
    Conversion of ribulose-5-phosphate to ribose-5-phosphate
    Back
    By isomerase
  43. Front
    Conversion of ribulose-5-phosphate to xylulose-5-phosphate
    Back
    By epimerase
  44. Front
    Importance of ribose-5-phosphate
    Back
    Needed for nucleotide and nucleic acid synthesis
  45. Front
    High-yield pentose summary
    Back
    Oxidative phase gives ribulose-5-phosphate, and nonoxidative rearrangements can give ribose-5-phosphate
  46. Front
    Functions of NADPH
    Back
    Anabolic processes, glutathione reduction, ribonucleotide reduction, cytochrome P450 detoxification, and nitric oxide synthesis
  47. Front
    NADPH use in anabolic processes
    Back
    Fatty acid synthesis and steroid synthesis
  48. Front
    NADPH role in RBCs
    Back
    Reduction of glutathione to maintain reduced glutathione levels
  49. Front
    NADPH role in nucleotide metabolism
    Back
    Reduction of ribonucleotides to deoxyribonucleotides
  50. Front
    NADPH role in detoxification
    Back
    Used in cytochrome P450 detoxification
  51. Front
    Additional NADPH-dependent process from Lippincott
    Back
    Nitric oxide synthesis by NADPH-dependent nitric oxide synthases
  52. Front
    Safest exam list of NADPH functions
    Back
    Fatty acid synthesis, steroid or cholesterol synthesis, glutathione reduction, ribonucleotide reduction, cytochrome P450 detoxification, and nitric oxide synthesis
  53. Front
    PPP tissue importance in adrenal tissue
    Back
    Steroid hormone synthesis
  54. Front
    PPP tissue importance in liver
    Back
    Fatty acid synthesis, cholesterol synthesis, detoxification, and reduction of glutathione
  55. Front
    PPP tissue importance in testes and ovaries
    Back
    Steroid synthesis
  56. Front
    PPP tissue importance in RBCs
    Back
    Maintaining reduced glutathione (GSH) levels
  57. Front
    High-yield RBC PPP concept
    Back
    RBCs need PPP mainly for NADPH to keep glutathione reduced
  58. Front
    Nature of the nonoxidative arm of PPP
    Back
    Reversible sugar-shuffling pathway
  59. Front
    Main job of the nonoxidative arm
    Back
    Interconvert sugars with 3 to 7 carbons
  60. Front
    Purpose of the nonoxidative arm
    Back
    Allows the cell to adapt depending on whether it needs more ribose-5-phosphate, NADPH, or glycolytic intermediates
  61. Front
    Isomerase reaction in the nonoxidative arm
    Back
    Ribulose-5-phosphate ⇌ ribose-5-phosphate
  62. Front
    Epimerase reaction in the nonoxidative arm
    Back
    Ribulose-5-phosphate ⇌ xylulose-5-phosphate
  63. Front
    Function of transketolase
    Back
    Transfers 2-carbon fragments
  64. Front
    Cofactor required by transketolase
    Back
    TPP (thiamine pyrophosphate)
  65. Front
    Function of transaldolase
    Back
    Transfers 3-carbon fragments
  66. Front
    High-yield distinction between transketolase and transaldolase
    Back
    Transketolase transfers 2-carbon units and requires TPP, whereas transaldolase transfers 3-carbon units
  67. Front
    Major glycolytic end products of the nonoxidative arm
    Back
    Fructose-6-phosphate and glyceraldehyde-3-phosphate
  68. Front
    Why PPP is tightly linked to glycolysis
    Back
    Nonoxidative PPP can generate F6P and GAP, which are glycolytic intermediates
  69. Front
    Importance of the nonoxidative arm
    Back
    Allows the cell to balance the need for ribose-5-phosphate, NADPH, and ATP
  70. Front
    Lecture principle determining PPP flux pattern
    Back
    The need for ribose-5-phosphate, NADPH, and ATP is decisive
  71. Front
    Situation when more ribose-5-phosphate than NADPH is needed
    Back
    Ribose-5-phosphate can be made from glycolytic intermediates without strongly using the oxidative NADPH-producing steps
  72. Front
    Classic example of needing ribose-5-phosphate more than NADPH
    Back
    Rapidly dividing cells needing nucleotides
  73. Front
    Situation when ribose-5-phosphate and NADPH are needed in balanced amounts
    Back
    The oxidative phase runs and ribulose-5-phosphate is converted to ribose-5-phosphate so both products are used
  74. Front
    Situation when much more NADPH than ribose-5-phosphate is needed
    Back
    The oxidative phase makes NADPH, and the nonoxidative phase recycles excess pentose phosphates into F6P and GAP
  75. Front
    How excess pentose phosphates are handled when NADPH demand is high
    Back
    Converted by the nonoxidative arm into F6P and GAP, which can re-enter glycolysis or regenerate G6P
  76. Front
    High-yield role of the nonoxidative arm
    Back
    It is a flexible connector between PPP and glycolysis
  77. Front
    Irreversible oxidative PPP summary
    Back
    G6P → 6-phosphogluconolactone by G6PD with NADPH formation, then 6-phosphogluconolactone → 6-phosphogluconate, then 6-phosphogluconate → ribulose-5-phosphate + CO2 by 6-phosphogluconate dehydrogenase with NADPH formation
  78. Front
    Reversible nonoxidative PPP summary
    Back
    Ribulose-5-phosphate interconverts with ribose-5-phosphate and xylulose-5-phosphate, and transketolase and transaldolase reactions generate F6P and GAP
  79. Front
    Effect of G6PD deficiency on PPP
    Back
    Decreases the ability of the cell to make NADPH
  80. Front
    Why G6PD deficiency is most severe in RBCs
    Back
    RBCs use the PPP as their only source of NADPH
  81. Front
    Relative vulnerability of RBCs in G6PD deficiency
    Back
    RBCs are the most vulnerable cells
  82. Front
    Why other tissues are less affected by G6PD deficiency
    Back
    They have alternative sources of NADPH
  83. Front
    Role of NADPH in RBC antioxidant defense
    Back
    NADPH is needed by glutathione reductase to keep glutathione in the reduced form
  84. Front
    Role of reduced glutathione in RBCs
    Back
    Protects against free radicals and peroxides
  85. Front
    Mechanism of hemolysis in G6PD deficiency
    Back
    Low NADPH leads to low reduced glutathione, causing oxidative damage to hemoglobin and membrane proteins
  86. Front
    Oxidized hemoglobin inclusions in G6PD deficiency
    Back
    Heinz bodies
  87. Front
    Why RBCs hemolyze in G6PD deficiency
    Back
    RBCs become rigid and are removed by spleen and liver macrophages, causing hemolytic anemia
  88. Front
    Classic triggers of hemolysis in G6PD deficiency
    Back
    Oxidant drugs, fava beans, and severe infection
  89. Front
    Main clinical consequence of G6PD deficiency
    Back
    Hemolytic anemia
  90. Front
    When hemolysis occurs in G6PD deficiency
    Back
    Often during episodes of oxidant stress
  91. Front
    Additional clinical consequence of G6PD deficiency
    Back
    Jaundice
  92. Front
    Important neonatal consequence of G6PD deficiency
    Back
    Neonatal jaundice
  93. Front
    Inheritance pattern of G6PD deficiency
    Back
    X-linked
  94. Front
    Immediate biochemical problem in G6PD deficiency
    Back
    Decreased reduced glutathione
  95. Front
    Clean RBC logic chain for G6PD deficiency
    Back
    G6PD deficiency → decreased NADPH → decreased reduced glutathione → oxidative damage in RBCs → Heinz bodies and membrane damage → hemolysis
  96. Front
    Additional high-yield PPP fact about transketolase
    Back
    Transketolase requires TPP and its activity is decreased in thiamine deficiency
  97. Front
    High-yield location of PPP
    Back
    PPP occurs in the cytosol
  98. Front
    High-yield phase distinction in PPP
    Back
    Oxidative phase is irreversible and nonoxidative phase is reversible
  99. Front
    High-yield regulatory step of PPP
    Back
    G6PD is the committed, rate-limiting, regulated step
  100. Front
    High-yield NADPH yield of oxidative PPP
    Back
    Two NADPH are made per glucose-6-phosphate in the oxidative phase
  101. Front
    High-yield dehydrogenases of oxidative PPP
    Back
    G6PD and 6-phosphogluconate dehydrogenase
  102. Front
    High-yield role of PPP in nucleotide synthesis
    Back
    Provides ribose-5-phosphate for nucleotide synthesis
  103. Front
    High-yield functions of PPP-derived NADPH
    Back
    Fatty acid synthesis, steroid synthesis, glutathione reduction, cytochrome P450 detoxification, and ribonucleotide reduction
  104. Front
    High-yield RBC dependence on PPP
    Back
    RBCs depend on PPP as their only source of NADPH
  105. Front
    High-yield disease association of G6PD deficiency
    Back
    G6PD deficiency causes oxidant-induced hemolytic anemia
  106. Front
    Cheat-sheet main purpose of PPP
    Back
    Makes NADPH and ribose-5-phosphate, occurs in the cytosol, and starts from glucose-6-phosphate
  107. Front
    Cheat-sheet oxidative phase of PPP
    Back
    G6P → 6-phosphogluconolactone by G6PD with NADPH formation, 6-phosphogluconolactone → 6-phosphogluconate, and 6-phosphogluconate → ribulose-5-phosphate + CO2 by 6-phosphogluconate dehydrogenase with NADPH formation
  108. Front
    Cheat-sheet products of oxidative PPP
    Back
    2 NADPH, ribulose-5-phosphate, and CO2
  109. Front
    Cheat-sheet nonoxidative PPP
    Back
    Ribulose-5-phosphate interconverts with ribose-5-phosphate and xylulose-5-phosphate, transketolase requires TPP, transaldolase participates, and end products include F6P and GAP
  110. Front
    Cheat-sheet functions of NADPH
    Back
    Fatty acid synthesis, steroid or cholesterol synthesis, glutathione reduction, ribonucleotide reduction, cytochrome P450 detoxification, and nitric oxide synthesis
  111. Front
    Cheat-sheet G6PD deficiency
    Back
    Decreased NADPH, decreased reduced glutathione in RBCs, oxidative damage, Heinz bodies, hemolytic anemia, and triggers including oxidant drugs, fava beans, and infections

Study these 111 cards with spaced repetition. Klappa is a free flashcard app: it schedules every card with FSRS-6, studies a deck as flashcards, multiple choice, typed answers or a graded test, and imports your Anki decks. How Klappa schedules reviews.

Sign in to study