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15.2 - Lipid stores as energy sourrce: FFA

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  1. Front
    Big problem in fatty acid mobilization
    Back
    How to release free fatty acids from adipose TAG stores and transport hydrophobic free fatty acids in blood
  2. Front
    Stored fat form in adipose tissue
    Back
    Triacylglycerol
  3. Front
    Overall goal of mobilizing stored fat
    Back
    Release fatty acids, transport them in blood, and use them for energy
  4. Front
    Lipolysis
    Back
    Breakdown of triacylglycerol to free fatty acids and glycerol
  5. Front
    Key enzyme in lipolysis
    Back
    Hormone-sensitive lipase
  6. Front
    When lipolysis is active
    Back
    Fasted state
  7. Front
    Hormonal and metabolic state promoting lipolysis
    Back
    Low glucose, low insulin, high glucagon, and high adrenaline
  8. Front
    First step in glucagon-stimulated lipolysis
    Back
    Glucagon binds its receptor
  9. Front
    Second step in glucagon-stimulated lipolysis
    Back
    Increased cAMP
  10. Front
    Third step in glucagon-stimulated lipolysis
    Back
    Activation of protein kinase A
  11. Front
    Fourth step in glucagon-stimulated lipolysis
    Back
    Phosphorylation of hormone-sensitive lipase, making it active
  12. Front
    Perilipin
    Back
    Protein coating fat droplets that must be phosphorylated to allow lipase access
  13. Front
    Effect of perilipin phosphorylation
    Back
    Allows lipases to access stored triacylglycerol in fat droplets
  14. Front
    How free fatty acids are transported in blood
    Back
    They bind to albumin
  15. Front
    Why free fatty acids require albumin in blood
    Back
    They are hydrophobic and cannot travel freely alone
  16. Front
    Full lipolysis pathway
    Back
    TAG is converted to DAG by ATGL, DAG to MAG by HSL, and MAG to glycerol and fatty acid by MGL
  17. Front
    ATGL
    Back
    Adipose triglyceride lipase that converts triacylglycerol to diacylglycerol
  18. Front
    HSL in the full lipolysis pathway
    Back
    Converts diacylglycerol to monoacylglycerol
  19. Front
    MGL
    Back
    Monoacylglycerol lipase that converts monoacylglycerol to glycerol and fatty acid
  20. Front
    Fate of free fatty acids after lipolysis
    Back
    They bind albumin in blood, enter tissues, and undergo oxidation
  21. Front
    Problem before fatty acid oxidation
    Back
    Free fatty acids cannot be used directly
  22. Front
    Required activation step before oxidation
    Back
    Fatty acids must be converted to acyl-CoA
  23. Front
    Acyl-CoA
    Back
    Activated form of a fatty acid
  24. Front
    Enzyme that activates fatty acids
    Back
    Acyl-CoA synthetase
  25. Front
    Other name for acyl-CoA synthetase
    Back
    Thiokinase
  26. Front
    Energy cost of fatty acid activation
    Back
    Two ATP equivalents
  27. Front
    First step of fatty acid activation
    Back
    Fatty acid reacts with ATP to form fatty acyl-AMP
  28. Front
    Second step of fatty acid activation
    Back
    CoA replaces AMP to form acyl-CoA
  29. Front
    Why fatty acid activation is necessary
    Back
    It is required before oxidation can occur
  30. Front
    Location of long-chain fatty acid activation
    Back
    Cytosol or outer mitochondrial membrane
  31. Front
    Location of medium-chain fatty acid activation
    Back
    Mitochondrial matrix
  32. Front
    Location of very-long-chain fatty acid activation
    Back
    Peroxisomes
  33. Front
    Exam focus for fatty acid activation
    Back
    Long-chain fatty acids
  34. Front
    Problem with mitochondrial entry of acyl-CoA
    Back
    Acyl-CoA cannot cross the inner mitochondrial membrane
  35. Front
    Solution for long-chain fatty acid entry into mitochondria
    Back
    Carnitine shuttle
  36. Front
    Components of the carnitine shuttle
    Back
    CPT I, carnitine, and CPT II
  37. Front
    CPT I
    Back
    Carnitine palmitoyltransferase I on the outer mitochondrial membrane that forms acyl-carnitine
  38. Front
    Role of carnitine in fatty acid transport
    Back
    Carrier that transports the fatty acyl group into mitochondria
  39. Front
    CPT II
    Back
    Carnitine palmitoyltransferase II that regenerates acyl-CoA inside mitochondria
  40. Front
    First step of the carnitine shuttle
    Back
    Acyl-CoA and carnitine are converted to acyl-carnitine by CPT I
  41. Front
    Second step of the carnitine shuttle
    Back
    Acyl-carnitine is transported into the mitochondrion
  42. Front
    Third step of the carnitine shuttle
    Back
    Acyl-carnitine is converted back to acyl-CoA by CPT II
  43. Front
    Key regulator of CPT I
    Back
    Malonyl-CoA
  44. Front
    Effect of malonyl-CoA on CPT I
    Back
    Inhibits CPT I
  45. Front
    Metabolic meaning of malonyl-CoA inhibition of CPT I
    Back
    If fatty acid synthesis is active, fatty acid oxidation is turned off
  46. Front
    Location of beta-oxidation
    Back
    Mitochondria
  47. Front
    Beta-oxidation
    Back
    Process that breaks fatty acids into acetyl-CoA units
  48. Front
    Products of beta-oxidation
    Back
    Acetyl-CoA, NADH, and FADH2
  49. Front
    Energy yield concept of fatty acid oxidation
    Back
    Fatty acids produce large amounts of ATP
  50. Front
    Comparison of fat and glucose energy yield
    Back
    Lipids produce more ATP than carbohydrates
  51. Front
    Energy density of fat
    Back
    Fat is more energy dense than glucose
  52. Front
    ATP calculation concept for palmitate
    Back
    Palmitate yields a high amount of ATP
  53. Front
    Unsaturated fatty acids in beta-oxidation
    Back
    Require extra enzymes
  54. Front
    Polyunsaturated fatty acids in beta-oxidation
    Back
    Require two extra enzymes
  55. Front
    Effect of unsaturation on ATP yield
    Back
    Makes oxidation more complex and yields slightly less ATP
  56. Front
    Final product of odd-chain fatty acid oxidation
    Back
    Propionyl-CoA
  57. Front
    Difference in odd-chain fatty acid oxidation
    Back
    Ends with a 3-carbon propionyl-CoA instead of acetyl-CoA
  58. Front
    Enzyme for odd-chain fatty acid metabolism step 1
    Back
    Propionyl-CoA carboxylase
  59. Front
    Enzyme for odd-chain fatty acid metabolism step 2
    Back
    Methylmalonyl-CoA mutase
  60. Front
    Cofactor for propionyl-CoA carboxylase
    Back
    Biotin
  61. Front
    Cofactor for methylmalonyl-CoA mutase
    Back
    Vitamin B12
  62. Front
    Metabolic significance of odd-chain fatty acids
    Back
    They can contribute to gluconeogenesis
  63. Front
    Site of very-long-chain fatty acid processing
    Back
    Peroxisomes
  64. Front
    Factors regulating beta-oxidation
    Back
    Substrate availability, ATP levels, NAD positive, FAD, and carnitine levels
  65. Front
    Most important control point of beta-oxidation
    Back
    CPT I
  66. Front
    Effect of high malonyl-CoA on fatty acid oxidation
    Back
    It inhibits CPT I and prevents fatty acid oxidation
  67. Front
    Full pathway of fatty acid use during fasting
    Back
    Lipolysis releases fatty acids, fatty acids travel bound to albumin, are activated to acyl-CoA, enter mitochondria through the carnitine shuttle, undergo beta-oxidation to form acetyl-CoA, NADH, and FADH2, and generate ATP through the electron transport chain
  68. Front
    Summary of lipolysis
    Back
    HSL is activated in fasting by glucagon and PKA signaling
  69. Front
    Summary of fatty acid transport
    Back
    Free fatty acids circulate bound to albumin
  70. Front
    Summary of fatty acid activation
    Back
    Fatty acids are converted to acyl-CoA at a cost of two ATP equivalents
  71. Front
    Summary of mitochondrial entry
    Back
    Long-chain fatty acids enter mitochondria via the carnitine shuttle using CPT I and CPT II
  72. Front
    Summary of beta-oxidation products
    Back
    Beta-oxidation produces acetyl-CoA, NADH, and FADH2
  73. Front
    Summary of regulation of beta-oxidation
    Back
    Malonyl-CoA inhibits CPT I

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