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13.) Fatty acid activation to acyl-CoA – reaction, its importance in lipid metabolism.

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  1. Front
    Fatty acid activation
    Back
    Conversion of a free fatty acid to fatty acyl-CoA
  2. Front
    Why fatty acid activation is necessary
    Back
    A free fatty acid is not yet ready to be oxidized, incorporated into TAG, incorporated into phospholipids, or used in most other lipid pathways
  3. Front
    Metabolically usable form of a fatty acid
    Back
    Fatty acyl-CoA
  4. Front
    Overall reaction of fatty acid activation
    Back
    Fatty acid + CoA-SH + ATP → fatty acyl-CoA + AMP + PPi
  5. Front
    First step of fatty acid activation
    Back
    Fatty acid + ATP → fatty acyl-AMP
  6. Front
    Second step of fatty acid activation
    Back
    Fatty acyl-AMP + CoA-SH → fatty acyl-CoA + AMP
  7. Front
    Activated intermediate in fatty acid activation
    Back
    Fatty acyl-AMP
  8. Front
    Product of fatty acid activation
    Back
    Fatty acyl-CoA
  9. Front
    ATP product of fatty acid activation
    Back
    AMP is produced, not ADP
  10. Front
    Enzyme for fatty acid activation
    Back
    Fatty acyl-CoA synthetase
  11. Front
    Other names for fatty acyl-CoA synthetase
    Back
    Acyl-CoA synthetase and thiokinase
  12. Front
    High-yield enzyme name for fatty acid activation
    Back
    Acyl-CoA synthetase or thiokinase
  13. Front
    Why ATP is used in fatty acid activation
    Back
    It forms an activated acyl-adenylate intermediate so CoA can attack and form the high-energy thioester bond of acyl-CoA
  14. Front
    Bond type formed in fatty acyl-CoA
    Back
    High-energy thioester bond
  15. Front
    Why fatty acyl-CoA is more reactive than a free fatty acid
    Back
    The thioester bond makes the fatty acid much more chemically reactive
  16. Front
    Energetic cost of fatty acid activation
    Back
    2 ATP equivalents
  17. Front
    Why fatty acid activation costs 2 ATP equivalents
    Back
    ATP is converted to AMP, so two high-energy phosphate bonds are effectively consumed
  18. Front
    High-yield energy fact for fatty acid activation
    Back
    Fatty acid activation costs 2 high-energy phosphate bonds
  19. Front
    Why β-oxidation ATP calculations subtract 2 ATP equivalents
    Back
    Fatty acid activation consumes 2 ATP equivalents before β-oxidation begins
  20. Front
    Need for activation before β-oxidation
    Back
    Free fatty acids are not oxidized directly and must first become fatty acyl-CoA
  21. Front
    Need for activation before TAG synthesis
    Back
    Fatty acids must be in activated acyl-CoA form before they can be incorporated into triacylglycerol
  22. Front
    Need for activation before phospholipid synthesis
    Back
    Phospholipid synthesis requires fatty acyl-CoA
  23. Front
    Need for activation before other complex lipid synthesis
    Back
    Fatty acyl-CoA is needed for synthesis of membrane lipids, phospholipids, sphingolipids, and storage TAG
  24. Front
    High-yield central role of fatty acyl-CoA
    Back
    Fatty acyl-CoA is the central usable form of a fatty acid in metabolism
  25. Front
    Importance of fatty acid activation in adipose tissue
    Back
    Dietary fatty acids taken up from chylomicrons or VLDL must first be activated to fatty acyl-CoA before storage as TAG
  26. Front
    Why fatty acid activation is required for efficient TAG synthesis
    Back
    Fatty acyl-CoA must combine with glycerol-3-phosphate to form TAG synthesis intermediates
  27. Front
    High-yield TAG synthesis fact
    Back
    No fatty acid activation means no efficient TAG synthesis
  28. Front
    Importance of fatty acid activation in phosphatidic acid formation
    Back
    Phosphatidic acid synthesis requires glycerol-3-phosphate to react with fatty acyl-CoA
  29. Front
    Why phosphatidic acid is important
    Back
    It is the key precursor for TAG and glycerophospholipids
  30. Front
    Importance of fatty acid activation in β-oxidation
    Back
    Fatty acid activation is the entry step that commits the fatty acid toward degradation
  31. Front
    High-yield β-oxidation fact
    Back
    Activation is the first required step before β-oxidation can proceed
  32. Front
    Metabolic compartment logic of fatty acyl-CoA
    Back
    Fatty acyl-CoA is a gateway branch point leading toward oxidation, storage TAG, and membrane lipids
  33. Front
    Useful mental model for fatty acid handling
    Back
    Free fatty acid is the transport or input form, whereas fatty acyl-CoA is the metabolically committed form
  34. Front
    Why CoA matters in fatty acid activation
    Back
    CoA forms a reactive thioester with the fatty acid rather than simply carrying it
  35. Front
    Why the thioester bond is important
    Back
    The thioester bond allows transfer of the fatty acyl group into β-oxidation intermediates, glycerol backbone in TAG, phosphatidic acid, and other lipids
  36. Front
    Clean flow of fatty acid activation
    Back
    FA + ATP → FA-AMP, then FA-AMP + CoA-SH → FA-CoA + AMP
  37. Front
    Main fates of fatty acyl-CoA
    Back
    β-Oxidation, TAG synthesis, phospholipid synthesis, and other complex lipid synthesis
  38. Front
    Very high-yield distinction about fatty acid form
    Back
    Free fatty acid is not the main directly usable metabolic form, whereas fatty acyl-CoA is
  39. Front
    Very high-yield reactants of fatty acid activation
    Back
    Activation uses ATP and CoA-SH
  40. Front
    Very high-yield ATP product of activation
    Back
    AMP is produced, so activation costs 2 ATP equivalents
  41. Front
    Very high-yield requirement before β-oxidation
    Back
    Acyl-CoA is required before β-oxidation
  42. Front
    Very high-yield requirement before TAG synthesis
    Back
    Acyl-CoA is required before TAG synthesis
  43. Front
    Very high-yield requirement for phosphatidic acid synthesis
    Back
    Acyl-CoA is required for phosphatidic acid synthesis, which is central for TAG and phospholipid synthesis
  44. Front
    Very high-yield lipid map fact
    Back
    Fatty acyl-CoA is a major branch point in lipid metabolism
  45. Front
    Cheat-sheet reaction for fatty acid activation
    Back
    Fatty acid + CoA-SH + ATP → fatty acyl-CoA + AMP + PPi via fatty acyl-AMP
  46. Front
    Cheat-sheet enzyme for fatty acid activation
    Back
    Fatty acyl-CoA synthetase, also called thiokinase
  47. Front
    Cheat-sheet energy cost of activation
    Back
    ATP is converted to AMP, so 2 high-energy phosphate bonds are used and the cost is 2 ATP equivalents
  48. Front
    Cheat-sheet importance of fatty acid activation
    Back
    Required before β-oxidation, TAG synthesis, phosphatidic acid formation, and phospholipid or complex lipid synthesis
  49. Front
    Cheat-sheet core idea of fatty acid activation
    Back
    Fatty acyl-CoA is the activated, metabolically usable form of a fatty acid

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