bio 210

• Lipoproteins


  Distribute cholesterol and triacylglycerols (TG), from the intestine and the liver, to peripheral tissues

  
• Free fatty acids and triacylglycerols

  Transported between organs and tissues
• Lipoproteins


  • Composed of hydrophilic, hydrophobic and amphipathic molecules

  
• Plasma lipoproteins


  Particles of different size and density

  
• Lipoprotein classes


  • Chylomicrons
  • Very low-density lipoproteins
  • Remnant particles
  • Low-density lipoproteins
  • High-density lipoproteins

  
• Apolipoproteins


  Protein components of lipoprotein particles. Their role is both structural and metabolic

  
• Apolipoproteins


  • Proteins with the letter B are structural, proteins without B are metabolic
  • Structural proteins can't be exchanged, metabolic proteins can be exchanged
• ApoAI and apoAII


  Main apolipoproteins in HDL particles. They activate lecithin:cholesterol acyltransferase (LCAT)

  
• ApoAI


  Has anti-inflammatory and antioxidant properties, and is a marker of HDL concentration
• ApoAII


  Activates cholesterol ester transfer protein (CETP), and inhibits lipoprotein lipase (LPL)

  
• ApoB100


  Controls the metabolism of LDL, and is the sole protein on the LDL particle. It is synthesized in the liver

  
• ApoB48


  Truncated form of ApoB100, present in chylomicrons. Synthesized in the intestine and does not bind to the LDL receptor
• ApoCI, CII, and CIII

  Act as enzyme activators and inhibitors, and are extensively exchanged between different lipoprotein classes

  
• ApoE


  Present in all lipoprotein classes except LDL. Binds to the LDL receptor and LDL-receptor-related protein (LRP). Stimulates LPL, HTGL and LCAT. Also synthesized in the brain and affects growth and repair of CNS cells

  
• LDL receptor


  Mediates cellular uptake of intact LDL particles
• Scavenger receptor


  Internalizes chemically modified (e.g. oxidized) LDL
• Lipoprotein lipase (LPL)


  Removes triacylglycerols from lipoprotein particles. Bound to endothelial cells and digests triacylglycerols in chylomicrons and VLDL

  
• Hepatic triglyceride lipase (HTGL)


  Removes triacylglycerols from lipoprotein particles. Associated with liver plasma membranes and acts on particles already partially digested by LPL

  
• Lecithin:cholesterol acyltransferase (LCAT)


  Esterifies cholesterol that HDL acquires from cells. Activated by apoAI

  
• Acyl-CoA:acylcholesterol transferase (ACAT)


  Esterifies cholesterol within cells
• Cholesterol ester transfer protein (CETP)


  Facilitates the exchange of cholesteryl esters for triacylglycerols between HDL and VLDL/IDL

  
• Fuel transport pathway


  1. Chylomicrons transport triglycerides to periphery, where LPL hydrolyzes them

  2. VLDL particles transport fuel from liver to peripheral tissues

  3. Triglyceride-rich particles acquire cholesteryl esters from HDL in exchange for triglycerides
• Overflow pathway


  1. LDL particles generated from remnants in fuel transport pathway

  2. LDL taken up by apoB/E receptor in response to decreased intracellular cholesterol
• Reverse cholesterol transport


  1. HDL particles assembled in liver and intestine

  2. HDL acquire cholesterol from cell membranes through ABCA1 transporter

  3. LCAT esterifies acquired cholesterol

  4. CETP facilitates exchange of apolipoproteins and cholesteryl esters between HDL and triglyceride-rich lipoproteins

  5. HDL-2 particles bind to scavenger receptor B1 on hepatocytes and transfer cholesteryl esters to liver
• Familial hypercholesterolemia (FH)


  Caused by mutations in apoB/E receptor or LDL receptor recycling, leading to very high plasma cholesterol and LDL
• Familial combined hyperlipidemia


  Overproduction of apoB100, leading to increased VLDL and LDL generation
• Familial dysbetalipoproteinemia


  Caused by mutation in apoE gene, leading to remnant accumulation and increased cholesterol and triglyceride
• Lipoprotein lipase deficiency


  Very rare, caused by LPL deficiency, leading to chylomicron and VLDL accumulation and very high plasma triglycerides

  
• Abetalipoproteinemia


  Mutation of microsomal transfer protein (MTP), leading to low VLDL and LDL concentrations