Lipoproteins S1M3

  1. Lipoproteins are composed of
    A neutral lipid core, surrounded by a shell of amphipathic apolipoproteins, phospholipids, and nonesterfied cholesterol.
  2. What makes the lipoproteins water soluble
    The amphiphatic compounds are oriented with their polar portions exposed on the surface.
  3. What are the lipoproteins largest in size, lowest in density, contain the highest percent of lipid, and lowest amount of protein
  4. What is the order of the lipoproteins from most dense to least dense
    • HDL
    • LDL
    • IDL
    • VLDL
    • Chylomicrons
  5. Apolipoproteins function
    Provide recognition sites for cell surface receptors, act as coenzymes and activators for enzymes in lipoprotein metabolism
  6. Where are chylomicrons assembled
    Intestinal mucosal cells
  7. What do chylomicrons carry
    Dietary triacylglycerol (TAG's), cholesterol, fat soluble vitamins, and cholesteryl esters to peripheral tissues
  8. What accounts for close to 90% of the chylomicrons
    Triacylglycerol (TAG's)
  9. What apolipoprotein is unique to only chylomicrons
    Apolipoprotein B-48
  10. Apolipoprotein B-48 begins synthesis where
    In the rough ER, and is then moved through the RER and the golgi where it is glycosylated
  11. Apo B-100 is made where and found on what lipoproteins
    • Liver
    • VLDL, IDL, and LDL
  12. Where are the enzymes located that synthesize tiacylglycerol, cholesterol, and phospholipids
    In the ER
  13. What is required to assemble apo's and lipids into chylomicrons
    Microsomal triacylglycerol transfer protein, which loads Apo B-48 with lipid
  14. What is a nascent chylomicron
    A functionally incomplete protein, these are released by the intestinal mucosal cells
  15. What is apo C-II necessary for
    They activation of lipoprotein lipase, the enzyme that degrades the triacylglycerol in chylomicrons
  16. What is the source for Apo C-II
    Circulating HDL
  17. Lipoprotein lipase
    Extracellular enzyme that degrades TAG's, it is anchored by heparan sulfate to the capillary walls of most tissues
  18. What tissues is lipoprotein lipase predominantly anchored to
    • Adipose, cardiac, and skeletal
    • The adult liver doesn't have it
  19. What happens to the free fatty acids and glycerol after being broken down by lipoprotein lipase
    • Free fatty acids go to the tissues
    • Glycerol goes to the liver
  20. When activated by apo C-II, what does lipoprotein lipase do
    Hydrolyzes the triacylglycerol contained on chylomicrons, LDL, VLDL, and HDL to yield fatty acids and glycerol
  21. Where are the fatty acids stored
    In the adipose tissues and used by muscles for energy
  22. What happens to fatty acids if they are not directly taken up by the cell
    They are transported by serum albumin until they are taken up
  23. What does the liver use glycerol for
    • Lipid synthesis
    • Glycolysis
    • Gluconeogenesis
  24. What happens in patients that lack lipoprotein lipase or apo C-II
    They show an accumulation of chylomicrons in their plasma (hypertriacylglycerolemia)
  25. How is the activity of lipoprotein lipase regulated
    Its synthesis and transfer to the luminal surface of the capillaries is stimulated by insulin
  26. Where is the highest concentration of lipoprotein lipase
    In the cardiac muscle (has a small Km for it as well)
  27. How does the liver recognize remnants of chylomicrons to degrade them
    By the apo-E on its surface
  28. What happens in the liver to the chylomicron remnants
    The endocytosed vesicle fuses with lysosomes where the apo's and cholesteryl esters are degraded releasing amino acids, free cholesterol, and fatty acids.
  29. What are the events that lead to the metabolism of chylomicrons (CM)
    • Intestinal mucosal cells secrete nascent CM with Apo-48 on their surface
    • Apo C-II + apo-E are transferred from HDL to CM
    • CM enters the capillaries
    • Lipoprotein lipase degrades TAG in CM
    • Apo C-II is returned to HDL (Keeps Apo E)
    • CM is degraded by the liver
  30. VLDL's are produced where
  31. What is the function of VLDL's
    To carry TAG's from the liver to the peripheral tissues
  32. What molecular activity causes fatty liver (hepatic steatosis)
    Inbalance between hepatic TAG's synthesis and secretion of VLDL's
  33. What are some causes of fatty liver (hepatic steatosis)
    • Diabetes
    • Obesity
    • Chronic ethanol ingestion
  34. VLDL's covered in apo B-100 are secreted by liver and then do what
    They must obtain C-II and apo-E from circulating HDL
  35. After VLDL is degraded by LPL, what happens to the C and E apo's
    They are returned to the HDL, but they retain B-100
  36. What causes the transfer of cholesteryl esters from HDL to VLDL so it can be disposed
    Cholesteryl ester transfer protein (CETP)
  37. What are the events that lead to the metabolism of VLDL and LDL
    • Liver secretes nascent TAG rich VLDL (apo B-100 on its surface)
    • VLDL acquires C-II + apo E form HDL
    • VLDL enters the capillaries
    • TAG in VLDL is degraded by LP lipase
    • Apo C-II and apo E are returned to HDL
    • The liver takes up the LDL
  38. LDL has a lower amount of TAG's then VLDL but a higher amount of
    Cholesterol and cholesteryl esters
  39. What is the primary function of LDL
    To provide cholesterol to the peripheral tissues, or return it to the liver
  40. LDL surface receptors recognize
    apo B-100 and apo E, but not apo B-48
  41. How do LDL deliver cholesteryl esters
    • They bind to a plasma membrane via a clathrin coated pit
    • It is internalized by endocytosis
    • Clathrin coat degrades and the vesicle fuses with others making an endosome
    • High pH causes LDL to separate from its receptor
    • The cholesteryl esters are released as free cholesterol, fatty acids, amino acids, and phospholipids
  42. HMG CoA reductase does what, and is inhibited by
    Sythesizes cholesterol in the cell when it doesn't have enough, it is inhibited by high cholesterol, triggered by insulin
  43. Synthesis of LDL receptors is inhibited by
    High cholesterol
  44. What is the role of Acyl CoA: cholesterol acyltransferase (ACAT)
    When cholesterol isn't needed for immediate structural or a synthetic purpose, it stores it in cells
  45. What lipoproteins are most likely to cause a Hypertriglyceridemic response
    • Chylomicron
    • VLDL
    • IDL
  46. What lipoprotein brings the dietary fats (exogenous) into the body
  47. What is the carrier for endogenous lipids
  48. What is good about a high HDL3
    It will lower the risk of heart disease
  49. What is apo A-I associated with
    Chylomicrons and HDL, it activates LCAT (HDL esterfier)
  50. Apo A-II is associated with what lipoproteins
    Chylomicrons and HDL, it enhances hepatic lipase activity
  51. LDL contains only what apo
    Apo B-100
  52. Apo B-100 is found on what lipoproteins
    • VLDL
    • IDL
    • LDL
  53. Apo C-I and C-II and C-III are found on what lipoproteins
    • Chylomicrons
    • VLDL
    • IDL
    • HDL
  54. What is the important role of C-II
    It activates lipoprotein lipase
  55. Apo C-III is associated with what lipoproteins and has what function
    • Chylomicrons
    • VLDL
    • IDL
    • HDL
    • Inhibits lipoprotein lipase
  56. Apo D is found on what lipoprotein and performs what function
    HDL, it is closely associated with LCAT (Esterfies cholesterol in HDL)
  57. Cholesterol ester transfer protein (CETP) is exclusively associated with and does what
    HDL, and transfers cholesterol esters from HDL particle into VLDL and IDL that can be taken up by the liver and disposed
  58. Apo E associates with
    • Chylomicron remnants
    • VLDL
    • IDL
    • HDL
    • Binds B/E receptors on hepatocytes and associated with Alzheimers (E4)
  59. Apo H is found on
    Chylomicrons, for TAG metabolism
  60. What is the significance of Apo A-1
    • It helps HDL dock on cells without a receptor
    • Activates the transfer of fatty acids, and esterfies cholesterol
  61. LPL hydrolyzes what from chylomicrons to place into adipose tissue
    Fatty acids
  62. What does lecithin cholesterol acyl transferase LCAT do
    It esterfies cholesterol in HDL
  63. Cholesterol is always stored how
    As Cholestryl ester (esterfied cholesterol)
  64. Hepatic lipase
    Further removes fats from IDL to create an LDL particle for binding, and participates in conversion of HDL2 to HDL3
  65. Apo is structurally homologous to what, and why is that significant
    Plasminogen, it is believed that elevated lipoprotein (containing Apo's) slows down the breakdown of clots because it competes with plasminogen
  66. What is the importance of T3
    T3 stimulates the breakdown of cholesterol and increases the number of LDL receptors, therefore increasing the rate of lipolysis.
  67. What substances inhibit the synthesis of intracellular cholesterol
    • "GC SLiM"
    • Glucagon
    • Cortisol
    • Simvastatin
    • Lovastatin
    • Mevastatin
  68. What are the steps to making intracellular cholesterol
    • Acetyl-CoA
    • HMG-CoA
    • Mevalonate
    • Intracellular cholesterol
  69. What are the stages of plaque formation in the arteries
    • Endothelial injury in vessel by oxidized LDL
    • Monocytes migrate to site, become macrophages
    • Macrophages become foam cells by consuming oxidized lipoproteins
    • Foam cells release growth factors and cytokines
    • Smooth muscle cells migrate from media triggered by cytokines and growth factors
    • Smooth muscle cells proliferate producing collagen, taking up lipids, and making foam cells
  70. Weight gain has what effect on plasma lipids
    Decrease HDL, increase VLDL
  71. Hypothyroidism effects what plasma lipid
    Increase in LDL by decreasing T3 receptors
  72. What does type I inherited hyperlipoproteinemia effect and how is it treated
    • Deficiency in LPL and C-II
    • Epigastric pain and turbid retina
    • Treat with low fat, high carb diet, and Gemifibrozil
  73. What does type IIa inherited hyperlipoproteinemia effect, and how is it treated
    • 4 classes of LDL receptors become defective
    • Coronary heart disease and plaques result
    • Treat with Statin or Resin
  74. What does type III inherited hyperlipoproteinemia effect
    • Apo E2
    • Causes Xanthomas, coronary heart disease and plaques
    • Treat with Niacin, Statin, or Gemfibrozil
  75. What does type IV inherited hyperlipoproteinemia effect
    • "4 diabetes hit the door!"
    • Elevated VLDL associated with glucose and high insulin
    • Treat with Niacin, Gemfibrozil
  76. What does type IIb inherited hyperlipoproteinemia effect
    • "2b most risky"
    • This is the most common
    • Increased LDL delayed clearance of VLDL
    • High risk of coronary heart disease
    • Treat with Niacin, or Statin
  77. Xanthelasmas
    Mole like collection of cholesterol usually around eyes, indicate hypercholesterolaemia in younger individuals
  78. Eruptive xanthomas
    Collection of cholesterol around body as bumps, common in older people with hypertriglyceridaemia
  79. Arcus sinilus
    White ring around the iris of the eye, often seen in hypercholesterolaemia
Card Set
Lipoproteins S1M3