Lipid metabolism

• Lipoprotein


  Transport vehicle for moving lipids around the body

  
• Components of lipoproteins


  • Cholesterol
  • Triglycerides
  • Phospholipids
  • Proteins

  
• Lipoprotein types


  Differ in the relative amounts of lipid and proteins, in their density, and in their functions

  
• Lipoprotein types


  • VLDL: very low density lipoprotein
  • LDL: low density lipoprotein
  • HDL: high density lipoprotein

  
• Lipoprotein metabolism


  1. Exogenous pathway

  2. Endogenous pathway

  
• Exogenous pathway


  1. Dietary fat (TG) is digested in the small intestines, via hydrolysis by pancreatic lipase and bile before being absorbed into the enterocytes

  2. Lipids are then packaged in the enterocytes in the form chylomicron

  3. Chylomicrons then enter the lymphatic system and later the systemic circulation

  
• Chylomicron


  Contains: core (TG and CE), surface (phospholipids, free cholesterol), apoproteins (apo B48, apo C-II, apo E)

  
• Exogenous pathway


  1. Chylomicrons interact with lipoprotein lipase (LPL) enzyme to hydrolyse TG to FA and glycerol

  2. This process results in the efficient transfer of dietary FA to muscle tissues and adipose tissue for oxidation and storage

  3. Hydrolysis of TG in the chylomicrons decrease the size chylomicron particles, leading to the formation of chylomicron remnants, enriched in cholesterol esters

  4. Chylomicron remnants are cleared from the circulation, the apo E on the chylomicron remnants binds to the LDL receptor on the liver and the particle is taken up by hepatocytes, CE is stored in the liver

  
• Endogenous pathway


  1. VLDL contains: core (TG and CE), surface (phospholipids, free cholesterol), apoproteins (apo B-100, apo C-II, apo E)

  2. VLDL particles hydrolyzed by LPL enzyme releasing FA to muscle tissues and adipose tissue

  3. Hydrolysis of TG in VLDL results in the formation of VLDL remnants (IDL)

  4. IDL particles are removed from the circulation by the liver via binding of Apo E to LDL receptors

  5. The remaining IDL particles are hydrolyzed by hepatic lipase, leading to a further decrease in particle size and formation of LDL

  6. LDL receptors circulates in the bloodstream, delivering CE to peripheral tissues, then returning to the liver and are cleared from the circulation via LDL receptor
• Reverse cholesterol transport


  1. HDL contains: Apo A-1, Apo C-II, Apo E, phospholipids

  2. Liver secretes lipid-poor HDL particles

  3. Lipid-poor HDL acquires lipid from muscle cells, fat cells, and other tissues that express ABCA1 transporter

  4. LCAT enzyme helps to esterify free cholesterol + fatty acids to form cholesterol ester, which then fills up the core of HDL, forming mature HDL

  5. HDL then delivers CE to the liver by binding with the SR-B1 receptor on the liver via apo A-1

  
• Reverse cholesterol transport plays an important role in the prevention of atherosclerosis