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15.4 - De novo synthesis of lipids: Saturated and Unsaturated FFA, complex lipids

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  1. Front
    Fed state and fat synthesis after a meal
    Back
    Glucose goes to the liver, is converted into triacylglycerol, and is exported as VLDL
  2. Front
    Key idea of the fed state in lipid synthesis
    Back
    Excess energy is stored as fat
  3. Front
    Sources of fatty acids for storage
    Back
    Dietary fat and carbohydrates
  4. Front
    Dietary source of stored fatty acids
    Back
    Triacylglycerol from the diet
  5. Front
    Carbohydrate source of stored fatty acids
    Back
    Glucose can be converted into fatty acids
  6. Front
    Main site of fatty acid synthesis
    Back
    Liver
  7. Front
    Other tissues that synthesize fatty acids
    Back
    Adipose tissue and mammary gland
  8. Front
    Cellular location of fatty acid synthesis
    Back
    Cytosol
  9. Front
    Type of fatty acid synthesis pathway
    Back
    Anabolic pathway
  10. Front
    Starting molecule for fatty acid synthesis
    Back
    Acetyl-CoA
  11. Front
    Reducing power used in fatty acid synthesis
    Back
    NADPH
  12. Front
    Key regulatory enzyme of fatty acid synthesis
    Back
    Acetyl-CoA carboxylase 1
  13. Front
    Problem of acetyl-CoA availability for synthesis
    Back
    Acetyl-CoA is produced in mitochondria but fatty acid synthesis occurs in the cytosol
  14. Front
    Solution for moving acetyl-CoA equivalents to the cytosol
    Back
    Citrate shuttle
  15. Front
    First step of the citrate shuttle
    Back
    Acetyl-CoA combines with oxaloacetate to form citrate
  16. Front
    What exits the mitochondrion during fatty acid synthesis
    Back
    Citrate
  17. Front
    Cytosolic reaction of citrate
    Back
    Citrate is cleaved to acetyl-CoA and oxaloacetate by citrate lyase
  18. Front
    Importance of citrate in fatty acid synthesis
    Back
    It carries 2-carbon acetyl units from mitochondria to cytosol
  19. Front
    What is exported from mitochondria for fatty acid synthesis
    Back
    Only 2-carbon acetyl units in the form of citrate
  20. Front
    Conditions that favor fatty acid synthesis
    Back
    High glucose and high ATP
  21. Front
    Meaning of high glucose and high ATP for lipid metabolism
    Back
    Energy excess turns fatty acid synthesis on
  22. Front
    First committed step of fatty acid synthesis
    Back
    Conversion of acetyl-CoA to malonyl-CoA
  23. Front
    Reaction catalyzed by ACC1
    Back
    Acetyl-CoA is carboxylated to malonyl-CoA
  24. Front
    Requirements for ACC1 reaction
    Back
    ATP and biotin
  25. Front
    Rate-limiting step of fatty acid synthesis
    Back
    Formation of malonyl-CoA by ACC1
  26. Front
    Fatty acid synthase
    Back
    A multi-enzyme complex that builds fatty acids
  27. Front
    Structure of fatty acid synthase
    Back
    Dimer with multiple enzyme activities
  28. Front
    ACP
    Back
    Acyl carrier protein that carries the growing fatty acid chain
  29. Front
    Key property of ACP
    Back
    It has an SH group
  30. Front
    Function of ACP
    Back
    Carries the growing fatty acid chain during synthesis
  31. Front
    Steps in each fatty acid synthase cycle
    Back
    Condensation, reduction, dehydration, reduction
  32. Front
    Reducing agent used in fatty acid synthase cycle
    Back
    NADPH
  33. Front
    How much the fatty acid chain grows per cycle
    Back
    Two carbons
  34. Front
    Final product of fatty acid synthase
    Back
    Palmitate
  35. Front
    Carbon length of palmitate
    Back
    Sixteen carbons
  36. Front
    Key idea of fatty acid synthase
    Back
    It builds fatty acids step by step using NADPH
  37. Front
    Main inputs for palmitate synthesis
    Back
    Acetyl-CoA, malonyl-CoA, and NADPH
  38. Front
    Main product of de novo fatty acid synthesis
    Back
    Palmitate
  39. Front
    Energy cost of fatty acid synthesis
    Back
    It is an energy-expensive process
  40. Front
    Location of fatty acid synthesis
    Back
    Cytosol
  41. Front
    Location of fatty acid oxidation
    Back
    Mitochondria
  42. Front
    Carrier used in fatty acid synthesis
    Back
    ACP
  43. Front
    Carrier used in fatty acid oxidation
    Back
    CoA
  44. Front
    Cofactor used in fatty acid synthesis
    Back
    NADPH
  45. Front
    Cofactors used in fatty acid oxidation
    Back
    NAD positive and FAD
  46. Front
    Why synthesis and oxidation do not occur simultaneously
    Back
    They are separated by location and use different enzymes, and malonyl-CoA inhibits fatty acid entry into mitochondria
  47. Front
    Levels of regulation of fatty acid synthesis
    Back
    Allosteric regulation, covalent modification, and enzyme expression
  48. Front
    Main control point of fatty acid synthesis
    Back
    ACC1
  49. Front
    Allosteric activator of ACC
    Back
    Citrate
  50. Front
    Allosteric inhibitor of ACC
    Back
    Palmitoyl-CoA
  51. Front
    Effect of citrate on ACC
    Back
    Activates ACC and promotes fatty acid synthesis
  52. Front
    Effect of palmitoyl-CoA on ACC
    Back
    Inhibits ACC and decreases fatty acid synthesis
  53. Front
    Effect of insulin on ACC
    Back
    Activates ACC
  54. Front
    Effect of insulin on fatty acid synthesis
    Back
    Increases fatty acid synthesis
  55. Front
    Effect of glucagon on ACC
    Back
    Inactivates ACC through phosphorylation
  56. Front
    Effect of adrenaline on ACC
    Back
    Inactivates ACC through phosphorylation
  57. Front
    Effect of glucagon and adrenaline on fatty acid synthesis
    Back
    Decrease fatty acid synthesis
  58. Front
    Malonyl-CoA connection to fatty acid oxidation
    Back
    Malonyl-CoA inhibits CPT I
  59. Front
    Why malonyl-CoA inhibits CPT I
    Back
    To prevent fatty acid oxidation when fatty acid synthesis is active
  60. Front
    Critical metabolic principle of lipid regulation
    Back
    The body cannot synthesize and oxidize fatty acids at the same time
  61. Front
    Regulation summary of fatty acid synthesis
    Back
    ACC is the major control point
  62. Front
    Full pathway from glucose to fatty acid
    Back
    Glucose becomes pyruvate, pyruvate becomes acetyl-CoA in mitochondria, acetyl-CoA becomes citrate and moves to the cytosol, citrate yields acetyl-CoA, ACC converts acetyl-CoA to malonyl-CoA, and fatty acid synthase produces palmitate
  63. Front
    Role of NADPH in fatty acid synthesis
    Back
    It provides reducing power for the reduction steps
  64. Front
    Why citrate is important in fatty acid synthesis
    Back
    It transports acetyl units to the cytosol and also activates ACC
  65. Front
    Effect of high insulin on fatty acid synthesis
    Back
    It increases fatty acid synthesis
  66. Front
    Why malonyl-CoA inhibits CPT I during fatty acid synthesis
    Back
    It blocks mitochondrial entry of fatty acyl-CoA so newly synthesized fat is not oxidized
  67. Front
    Cheat sheet location of fatty acid synthesis
    Back
    Liver cytosol
  68. Front
    Cheat sheet starting point of fatty acid synthesis
    Back
    Acetyl-CoA
  69. Front
    Cheat sheet key steps of fatty acid synthesis
    Back
    Citrate shuttle, ACC formation of malonyl-CoA, and fatty acid synthase formation of palmitate
  70. Front
    Cheat sheet requirements for fatty acid synthesis
    Back
    ATP and NADPH
  71. Front
    Cheat sheet regulation of fatty acid synthesis
    Back
    Citrate activates, palmitoyl-CoA inhibits, insulin activates, and glucagon inhibits
  72. Front
    Cheat sheet key link between synthesis and oxidation
    Back
    Malonyl-CoA inhibits CPT I

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