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16.1 - Metabolic fate of fatty acids

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  1. Front
    Metabolic fate of fatty acids
    Back
    What the body does with fatty acids after they are made.
  2. Front
    What fatty acids can do after synthesis
    Back
    Fatty acids can be elongated, desaturated, or used to form TAG fat storage and VLDL.
  3. Front
    Starting molecule for fatty acid modification
    Back
    Palmitate with 16 carbons.
  4. Front
    Palmitate (16C)
    Back
    Base fatty acid that is modified into other fatty acids or stored as fat.
  5. Front
    Fed state timing
    Back
    Occurs after eating in the postprandial state.
  6. Front
    First event in the fed state
    Back
    Glucose increases and goes to the liver.
  7. Front
    De novo synthesis
    Back
    Liver conversion of glucose to fatty acids.
  8. Front
    Main product of de novo fatty acid synthesis
    Back
    Palmitate 16C.
  9. Front
    Activated form of fatty acids
    Back
    Acyl-CoA.
  10. Front
    Two possible fates of activated fatty acids
    Back
    Oxidation for energy or storage as TAG.
  11. Front
    Liver TAG transport pathway
    Back
    Liver makes TAG, packages it into VLDL, releases it into blood, and delivers it to muscle and adipose tissue.
  12. Front
    High-yield fed state pathway
    Back
    Glucose → fatty acids → TAG → stored fat.
  13. Front
    Fatty acid elongation
    Back
    Making a fatty acid chain longer.
  14. Front
    Main site of fatty acid elongation
    Back
    Smooth endoplasmic reticulum.
  15. Front
    Minor site of fatty acid elongation
    Back
    Mitochondria.
  16. Front
    Starting molecule for elongation
    Back
    Palmitate 16C.
  17. Front
    Carbon addition pattern in elongation
    Back
    Two carbons are added at a time.
  18. Front
    Example of elongation
    Back
    Palmitate 16C can be elongated to stearate 18C.
  19. Front
    ER elongation carbon donor
    Back
    Malonyl-CoA.
  20. Front
    Steps of ER elongation
    Back
    Add 2 carbons from malonyl-CoA, reduction, dehydration, and reduction.
  21. Front
    Final product of ER elongation
    Back
    A longer saturated fatty acid.
  22. Front
    Carrier difference between elongation and fatty acid synthesis
    Back
    Elongation uses CoA, not ACP.
  23. Front
    Reducing power used in elongation
    Back
    NADPH.
  24. Front
    Mitochondrial elongation substrate
    Back
    Acetyl-CoA.
  25. Front
    Relationship of mitochondrial elongation to β-oxidation
    Back
    It is the reverse of β-oxidation except for one step.
  26. Front
    Brain fatty acid elongation capability
    Back
    The brain can make very long fatty acids up to C24.
  27. Front
    Core concept of elongation
    Back
    Elongation adds 2 carbons and occurs in the ER using NADPH and malonyl-CoA.
  28. Front
    Fatty acid desaturation
    Back
    Adding double bonds to fatty acids.
  29. Front
    Site of desaturation
    Back
    Smooth endoplasmic reticulum.
  30. Front
    Desaturation reaction: palmitate
    Back
    Palmitate is converted to palmitoleate 16:1.
  31. Front
    Desaturation reaction: stearate
    Back
    Stearate is converted to oleate 18:1.
  32. Front
    Type of double bond inserted during desaturation
    Back
    A cis double bond.
  33. Front
    Example position of inserted double bond
    Back
    Between C9 and C10.
  34. Front
    Three-part desaturation enzyme system
    Back
    NADH-cytochrome b5 reductase, cytochrome b5, and desaturase.
  35. Front
    Human desaturation limitation
    Back
    Humans cannot insert double bonds beyond carbon 9.
  36. Front
    Consequence of human desaturation limitation
    Back
    Humans cannot make omega-3 or omega-6 fatty acids and must obtain them from the diet.
  37. Front
    Electron source for desaturation
    Back
    NADH and the fatty acid itself.
  38. Front
    Core concept of desaturation
    Back
    Desaturation inserts a double bond in the ER and is limited to the C4–C9 region.
  39. Front
    Sources of liver fatty acids
    Back
    De novo synthesis about 60 percent, chylomicron remnants, and intestine via the portal vein.
  40. Front
    Main source of liver fatty acids
    Back
    De novo synthesis contributes about 60 percent.
  41. Front
    Activated liver fatty acid intermediate
    Back
    Fatty acyl-CoA.
  42. Front
    Three fates of fatty acids in the liver
    Back
    β-oxidation for energy, membrane lipid synthesis, and storage as TAG.
  43. Front
    Liver as fatty acid hub
    Back
    The liver is the central hub for fatty acid processing.
  44. Front
    Cheat sheet: fed state
    Back
    Glucose → FA → TAG → VLDL → adipose.
  45. Front
    Cheat sheet: elongation
    Back
    Adds 2 carbons, occurs in ER, and uses malonyl-CoA plus NADPH.
  46. Front
    Cheat sheet: desaturation
    Back
    Adds a double bond, occurs in ER, and cannot go beyond C9.
  47. Front
    Cheat sheet: liver fatty acid sources
    Back
    De novo synthesis is the main source, with additional input from chylomicrons and the portal vein.
  48. Front
    Triacylglycerol (TAG)
    Back
    Storage form of fat made of 1 glycerol and 3 fatty acids.
  49. Front
    Components required for TAG synthesis
    Back
    Glycerol-3-phosphate and fatty acyl-CoA.
  50. Front
    Liver source of glycerol-3-phosphate from glucose
    Back
    Glucose enters glycolysis to form DHAP, which is converted to glycerol-3-phosphate.
  51. Front
    Liver source of glycerol-3-phosphate from glycerol
    Back
    Glycerol is converted directly to glycerol-3-phosphate.
  52. Front
    Core steps of TAG formation
    Back
    A glycerol-3-phosphate backbone is esterified with 3 fatty acyl-CoA molecules to form TAG.
  53. Front
    Fate of TAG after liver synthesis
    Back
    It is packaged into VLDL.
  54. Front
    Core concept of TAG synthesis
    Back
    TAG is the storage form of fat, made in the liver, and exported as VLDL.
  55. Front
    VLDL
    Back
    Very low density lipoprotein that transports TAG from the liver to tissues.
  56. Front
    Function of VLDL
    Back
    Transport TAG from liver to tissues.
  57. Front
    VLDL core components
    Back
    TAG as the main component and cholesterol esters.
  58. Front
    VLDL surface components
    Back
    Phospholipid layer, free cholesterol, and apoproteins.
  59. Front
    Apo B-100
    Back
    Integral protein present in VLDL, IDL, and LDL.
  60. Front
    Apo C-II
    Back
    Apoprotein that activates lipoprotein lipase.
  61. Front
    Apo E
    Back
    Apoprotein that helps uptake of remnants.
  62. Front
    Core concept of VLDL
    Back
    VLDL is a TAG-rich particle containing Apo B100 that transports fat out of the liver.
  63. Front
    Lipoprotein lipase (LPL)
    Back
    Enzyme that breaks down TAG in the blood.
  64. Front
    Location of LPL
    Back
    Attached to capillary endothelium, especially in adipose tissue, muscle, and heart.
  65. Front
    LPL reaction
    Back
    TAG in VLDL is hydrolyzed to fatty acids and glycerol.
  66. Front
    Fate of fatty acids released by LPL
    Back
    Fatty acids enter tissues.
  67. Front
    Fate of glycerol released by LPL
    Back
    Glycerol returns to the liver.
  68. Front
    Activator of LPL
    Back
    Apo C-II.
  69. Front
    Hormonal regulation of LPL
    Back
    Insulin increases LPL activity.
  70. Front
    Meaning of insulin increasing LPL activity
    Back
    After eating, more fat storage occurs.
  71. Front
    Core concept of LPL
    Back
    LPL releases fatty acids from VLDL for tissue uptake.
  72. Front
    First step of VLDL transport
    Back
    Liver releases VLDL containing TAG and Apo B100.
  73. Front
    Second step of VLDL transport
    Back
    VLDL enters blood and picks up Apo C-II from HDL.
  74. Front
    Third step of VLDL transport
    Back
    LPL acts on VLDL and converts TAG to fatty acids and glycerol.
  75. Front
    Fate of VLDL-derived fatty acids in muscle
    Back
    Used for energy through oxidation.
  76. Front
    Fate of VLDL-derived fatty acids in adipose tissue
    Back
    Re-formed into TAG and stored.
  77. Front
    Adipose LPL kinetic property
    Back
    Has a higher Km and is less active unless TAG levels are high.
  78. Front
    Muscle LPL kinetic property
    Back
    Has a lower Km and works even when TAG levels are low.
  79. Front
    Core concept of VLDL transport
    Back
    VLDL delivers fat, LPL releases fatty acids, and tissues either burn or store them.
  80. Front
    First step of final integrated pathway
    Back
    Liver makes fatty acids from glucose by de novo synthesis and from diet.
  81. Front
    Second step of final integrated pathway
    Back
    Liver converts fatty acids to TAG.
  82. Front
    Third step of final integrated pathway
    Back
    TAG is packaged into VLDL.
  83. Front
    Fourth step of final integrated pathway
    Back
    VLDL enters the bloodstream.
  84. Front
    Fifth step of final integrated pathway in adipose tissue
    Back
    Insulin activates LPL, and LPL breaks TAG into fatty acids.
  85. Front
    Sixth step of final integrated pathway
    Back
    Fatty acids enter adipocytes.
  86. Front
    Seventh step of final integrated pathway
    Back
    Fatty acids are re-esterified to TAG.
  87. Front
    Eighth step of final integrated pathway
    Back
    TAG is stored as lipid droplets.
  88. Front
    Most important core idea of 16.1
    Back
    Glucose → FA → TAG in liver → VLDL → LPL → FA → adipose → TAG storage.
  89. Front
    TAG synthesis requirements
    Back
    Glycerol-3-phosphate and fatty acyl-CoA.
  90. Front
    Key role of VLDL
    Back
    Transports TAG from the liver.
  91. Front
    Key apoprotein of VLDL
    Back
    Apo B100.
  92. Front
    Main action of LPL
    Back
    Breaks TAG into fatty acids and glycerol.
  93. Front
    LPL activator
    Back
    Apo C-II.
  94. Front
    LPL hormonal stimulation
    Back
    Insulin stimulates LPL.
  95. Front
    Tissue fate of delivered fatty acids in muscle
    Back
    Oxidation.
  96. Front
    Tissue fate of delivered fatty acids in adipose
    Back
    Storage.
  97. Front
    Whole pathway summary
    Back
    Liver → VLDL → LPL → FA → adipose storage.

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