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7.) PDH complex

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  1. Front
    Pyruvate dehydrogenase reaction
    Back
    Converts pyruvate to acetyl-CoA
  2. Front
    Location of the pyruvate dehydrogenase reaction
    Back
    Mitochondrial matrix
  3. Front
    What must happen before pyruvate undergoes the PDH reaction
    Back
    Pyruvate must be transported from the cytosol into mitochondria
  4. Front
    Major metabolic link formed by PDH
    Back
    Glycolysis is linked to the TCA cycle through conversion of pyruvate to acetyl-CoA
  5. Front
    High-yield flow involving PDH
    Back
    Glycolysis ends with pyruvate, PDH converts pyruvate to acetyl-CoA, and acetyl-CoA then enters the TCA cycle
  6. Front
    Overall PDH reaction
    Back
    Pyruvate + CoA + NAD+ → acetyl-CoA + CO2 + NADH + H+
  7. Front
    What happens to pyruvate carbon in the PDH reaction
    Back
    One carbon is released as CO2 and the remaining 2-carbon fragment becomes the acetyl group of acetyl-CoA
  8. Front
    Redox event in the PDH reaction
    Back
    NAD+ is reduced to NADH
  9. Front
    Type of reaction catalyzed by PDH
    Back
    Oxidative decarboxylation
  10. Front
    Why the PDH reaction matters
    Back
    It provides the major source of acetyl-CoA from glucose for the TCA cycle
  11. Front
    Importance of NADH produced by PDH
    Back
    It can later generate ATP through the respiratory chain
  12. Front
    Metabolic commitment created by PDH
    Back
    PDH commits glucose-derived carbon to oxidation in TCA or downstream anabolic uses of acetyl-CoA such as lipid synthesis pathways
  13. Front
    Why fatty acids cannot be converted back to glucose through PDH
    Back
    PDH is irreversible, so acetyl-CoA is not a gluconeogenic precursor
  14. Front
    Reversibility of the PDH reaction
    Back
    Irreversible
  15. Front
    Meaning of PDH irreversibility
    Back
    Once pyruvate becomes acetyl-CoA, it cannot be converted back to pyruvate by reversing PDH
  16. Front
    High-yield directionality of PDH
    Back
    Pyruvate can become acetyl-CoA, but acetyl-CoA cannot become pyruvate by PDH
  17. Front
    Why pyruvate is a branch point
    Back
    Pyruvate can go to lactate, alanine, oxaloacetate, or acetyl-CoA
  18. Front
    Why PDH is a metabolic commitment step
    Back
    Once pyruvate goes to acetyl-CoA, that carbon is committed away from lactate, alanine, or direct gluconeogenic return through pyruvate
  19. Front
    Enzyme form of PDH
    Back
    PDH is a multienzyme complex called the pyruvate dehydrogenase complex (PDHC or PDC)
  20. Front
    Catalytic enzymes of the PDH complex
    Back
    E1, E2, and E3
  21. Front
    E1 of the PDH complex
    Back
    Pyruvate decarboxylase or pyruvate dehydrogenase
  22. Front
    E2 of the PDH complex
    Back
    Dihydrolipoyl transacetylase
  23. Front
    E3 of the PDH complex
    Back
    Dihydrolipoyl dehydrogenase
  24. Front
    Regulatory enzymes of the PDH complex
    Back
    PDH kinase and PDH phosphatase
  25. Front
    Why PDH is organized as a multienzyme complex
    Back
    The enzymes are physically associated so intermediates are passed directly from one active site to the next without diffusing away
  26. Front
    High-yield advantages of the PDH multienzyme complex
    Back
    It increases efficiency and helps control reactive intermediates
  27. Front
    Five coenzymes used by the PDH complex
    Back
    TPP, lipoic acid, CoA, FAD, and NAD+
  28. Front
    Coenzyme used by E1
    Back
    TPP
  29. Front
    Coenzymes used by E2
    Back
    Lipoic acid and CoA
  30. Front
    Coenzymes used by E3
    Back
    FAD and NAD+
  31. Front
    Vitamin precursor of TPP
    Back
    Thiamine (vitamin B1)
  32. Front
    Vitamin precursor of FAD
    Back
    Riboflavin (vitamin B2)
  33. Front
    Vitamin precursor of NAD+
    Back
    Niacin (vitamin B3)
  34. Front
    Vitamin precursor of CoA
    Back
    Pantothenic acid (vitamin B5)
  35. Front
    Exception among PDH coenzymes for vitamin origin
    Back
    Lipoic acid
  36. Front
    Memory line for PDH coenzymes
    Back
    Tender Loving Care For Nancy
  37. Front
    T in Tender Loving Care For Nancy
    Back
    TPP
  38. Front
    L in Tender Loving Care For Nancy
    Back
    Lipoic acid
  39. Front
    C in Tender Loving Care For Nancy
    Back
    CoA
  40. Front
    F in Tender Loving Care For Nancy
    Back
    FAD
  41. Front
    N in Tender Loving Care For Nancy
    Back
    NAD+
  42. Front
    Conceptual role of TPP in PDH
    Back
    Helps with decarboxylation of pyruvate
  43. Front
    Conceptual role of lipoic acid in PDH
    Back
    Accepts the 2-carbon fragment and transfers it within the complex as a swinging arm
  44. Front
    Conceptual role of CoA in PDH
    Back
    Accepts the acetyl group to form acetyl-CoA
  45. Front
    Conceptual role of FAD in PDH
    Back
    Accepts electrons inside the complex
  46. Front
    Conceptual role of NAD+ in PDH
    Back
    Accepts electrons from reduced FAD to form NADH
  47. Front
    First step of the PDH mechanism
    Back
    E1 decarboxylates pyruvate, releasing CO2 with involvement of TPP
  48. Front
    Second step of the PDH mechanism
    Back
    The remaining 2-carbon fragment is transferred to lipoamide on E2
  49. Front
    Third step of the PDH mechanism
    Back
    E2 transfers the acetyl group to CoA to make acetyl-CoA
  50. Front
    Final step of the PDH mechanism
    Back
    E3 reoxidizes reduced lipoamide using FAD and then transfers electrons to NAD+ to make NADH
  51. Front
    Location comparison of glycolysis, PDH, and TCA
    Back
    Glycolysis is cytosolic, whereas PDH and the TCA cycle are mitochondrial
  52. Front
    Main role of PDH as a link reaction
    Back
    PDH connects glycolysis to the TCA cycle
  53. Front
    Main role of PDH in glucose metabolism
    Back
    It is the major source of acetyl-CoA from glucose
  54. Front
    Main role of PDH in energy production
    Back
    It produces NADH for oxidative phosphorylation
  55. Front
    PDH as a metabolic decision point
    Back
    It determines whether pyruvate carbon goes toward aerobic oxidation rather than lactate formation or gluconeogenesis
  56. Front
    Big-picture regulation of PDH
    Back
    PDH is regulated by covalent modification, product inhibition, and energy state
  57. Front
    Effect of PDH kinase on PDH
    Back
    PDH kinase phosphorylates E1 and inactivates PDH
  58. Front
    Effect of PDH phosphatase on PDH
    Back
    PDH phosphatase dephosphorylates E1 and activates PDH
  59. Front
    Phosphorylated state of PDH
    Back
    Inactive
  60. Front
    Dephosphorylated state of PDH
    Back
    Active
  61. Front
    What activates PDH kinase
    Back
    ATP, acetyl-CoA, and NADH
  62. Front
    Meaning of PDH kinase activation by ATP, acetyl-CoA, and NADH
    Back
    High-energy and high-product signals shut down further pyruvate oxidation through PDH
  63. Front
    What inhibits PDH kinase
    Back
    Pyruvate and ADP
  64. Front
    Meaning of PDH kinase inhibition by pyruvate and ADP
    Back
    High substrate or high energy demand favors keeping PDH active
  65. Front
    What activates PDH phosphatase
    Back
    Ca2+
  66. Front
    Why Ca2+ activation of PDH phosphatase matters in muscle and heart
    Back
    Contraction raises intracellular Ca2+, activating PDH phosphatase and increasing acetyl-CoA production for energy
  67. Front
    Effect of insulin on PDH according to Marks
    Back
    Insulin can rapidly activate PDH in some tissues, especially adipocytes
  68. Front
    Products that inhibit PDH
    Back
    Acetyl-CoA and NADH
  69. Front
    Why acetyl-CoA and NADH inhibit PDH
    Back
    If products are already abundant, the reaction slows
  70. Front
    Substrates that antagonize PDH product inhibition
    Back
    CoA-SH and NAD+
  71. Front
    Effect of high fatty acid oxidation on PDH regulation
    Back
    Fatty acid oxidation raises acetyl-CoA and NADH, which inhibit PDH directly or through activation of PDH kinase
  72. Front
    Integrated fasting effect on PDH
    Back
    In fasting, fatty acids provide abundant acetyl-CoA, glucose carbon is spared from oxidation, and pyruvate is more available for other pathways such as gluconeogenesis
  73. Front
    PDH compared with pyruvate carboxylase
    Back
    PDH converts pyruvate to acetyl-CoA, whereas pyruvate carboxylase converts pyruvate to oxaloacetate
  74. Front
    Irreversibility comparison between PDH and pyruvate carboxylase
    Back
    PDH is irreversible, whereas pyruvate carboxylase is a carboxylation reaction directing pyruvate to oxaloacetate
  75. Front
    Coenzyme distinction between PDH and pyruvate carboxylase
    Back
    PDH uses TPP, whereas pyruvate carboxylase uses biotin
  76. Front
    Role distinction between PDH and pyruvate carboxylase
    Back
    PDH links glycolysis to TCA, whereas pyruvate carboxylase is important for gluconeogenesis and anaplerosis
  77. Front
    Effect of thiamine deficiency on PDH
    Back
    Because TPP is required, thiamine deficiency impairs PDH activity
  78. Front
    Metabolic consequence of thiamine deficiency on PDH
    Back
    Impaired oxidative decarboxylation of pyruvate and reduced ATP generation, especially in the CNS
  79. Front
    Effect of PDH deficiency
    Back
    Decreased conversion of pyruvate to acetyl-CoA
  80. Front
    Why PDH deficiency causes lactic acidosis
    Back
    Pyruvate is shunted to lactate, causing lactate accumulation
  81. Front
    Effect of arsenite poisoning on PDH
    Back
    Arsenite inhibits lipoic acid-dependent enzyme complexes including PDH
  82. Front
    Why arsenite poisoning causes pyruvate and lactate accumulation
    Back
    PDH is inhibited, so pyruvate cannot be efficiently converted to acetyl-CoA and is diverted to lactate
  83. Front
    Super high-yield fact about PDH reversibility
    Back
    PDH is irreversible
  84. Front
    Super high-yield fact about PDH location
    Back
    PDH is in the mitochondrial matrix
  85. Front
    Super high-yield fact about PDH function
    Back
    It links glycolysis to the TCA cycle
  86. Front
    Super high-yield fact about PDH structure
    Back
    It is a multienzyme complex with E1, E2, and E3
  87. Front
    Super high-yield list of PDH coenzymes
    Back
    TPP, lipoic acid, CoA, FAD, and NAD+
  88. Front
    Super high-yield fact about PDH phosphorylation
    Back
    Phosphorylation inactivates PDH
  89. Front
    Super high-yield activators of PDH kinase
    Back
    ATP, acetyl-CoA, and NADH
  90. Front
    Super high-yield inhibitors of PDH kinase
    Back
    Pyruvate and ADP
  91. Front
    Super high-yield activator of PDH phosphatase
    Back
    Ca2+
  92. Front
    Super high-yield coenzyme distinction
    Back
    Biotin is not a PDH coenzyme; it belongs to carboxylases such as pyruvate carboxylase
  93. Front
    Cheat-sheet overall PDH reaction
    Back
    Pyruvate + CoA + NAD+ → acetyl-CoA + CO2 + NADH + H+
  94. Front
    Cheat-sheet role of PDH
    Back
    Major link between glycolysis and TCA, major source of acetyl-CoA from glucose, and producer of NADH
  95. Front
    Cheat-sheet irreversibility of PDH
    Back
    Irreversible and commits pyruvate carbon to acetyl-CoA formation
  96. Front
    Cheat-sheet PDH catalytic enzymes
    Back
    E1 pyruvate decarboxylase or dehydrogenase, E2 dihydrolipoyl transacetylase, and E3 dihydrolipoyl dehydrogenase
  97. Front
    Cheat-sheet PDH coenzymes
    Back
    TPP, lipoic acid, CoA, FAD, and NAD+
  98. Front
    Cheat-sheet PDH regulation
    Back
    PDH kinase phosphorylates and inactivates PDH, PDH phosphatase dephosphorylates and activates PDH, kinase is activated by ATP, acetyl-CoA, and NADH, kinase is inhibited by pyruvate and ADP, phosphatase is activated by Ca2+, and insulin can activate PDH in some tissues

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