Everything about Lipoproteins

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Introduction

Chylomicron:

  • Maximum size
  • Maximum triglyceride content
  • Minimum protein content
  • Minimum cholesterol content.

LDL:

  • Maximum cholesterol content
  • BAD cholesterol.

HDL:

  • Maximum protein content
  • Minimum triglyceride content
  • Storehouse of apolipoproteins (C2 & E)
  • Aids in reverse cholesterol transport
  • GOOD cholesterol
  • BEST marker for cardiovascular diseases: Low HDL.

 

Centrifugation:

From above to downwards: C-VILH

 

Electrophoresis:

From above to downwards: C-LIVH

Synthesis of chylomicron & VLDL

  • Synthesis of both chylomicron and VLDL needs a protein called MTTP (Microsomal triglyceride transfer protein)
  • MTTP protein transfers B48 & B100 to triglyceride to make chylomicron & VLDL in the ER of intestine & liver respectively

  • Remember: Apo-B48 is produced from Apo-B100 by RNA editing
  • Deficiency of MTTP leads to Abetalipoproteinemia (Bassen-Kornzweig syndrome) – Absent chylomicron, VLDL & LDL with normal HDL
  • Clinical features of Abetalipoproteinemia:  Intestinal malabsorption and acanthocytes (RBC with spiked cell membrane) in blood.

Further transport and fate of chylomicron and VLDL are similar:

  • In blood, HDL acts as a donor of Apo-C2 & Apo-E, donating these 2 apolipoproteins to chylomicron/ VLDL
  • Apo-C2 activates Lipoprotein lipase attached to the wall of blood vessel
  • Lipoprotein lipase degrades the triglyceride to fatty acid, glycerol & chylomicron remnants/ VLDL remnants (IDL)
  • Chylomicron remnants/ IDL has Apo-E attached to them
  • Liver has receptors for Apo-E
  • So, these chylomicron remnants/ IDL are endocytosed and degraded in the liver.

Type 1 hyperlipoproteinemia:

  • Deficiency of apo-C2 or Lipoprotein lipase
  • Results in very high triglyceride level
  • High risk of pancreatitis.

Type 3 hyperlipoproteinemia:

  • Defective apo-E
  • Defective clearance of chylomicron remnants and VLDL remnants (IDL) in liver
  • Blood test: High triglyceride & high total cholesterol
  • Clinical finding: Palmar crease xanthoma.

Synthesis of LDL and relation with HDL:

HDL: Reverse cholesterol transport:

Type 2 hyperlipoproteinemia:

  • Deficiency of LDL receptors in the cells
  • High LDL level in blood
  • Clinical finding: Tendon xanthoma (localized lipid deposits within organs that may manifest as papules, plaques, or nodules in skin).

Summary:

Special note: Lp(a):

  • Lp(a) is a risk factor for atherosclerosis because Lp(a) has structural homology with plasminogen
  • So, Lp(a) competes with plasminogen for binding to fibrin, so fibrin is not lysed, resulting in an increase in thrombotic events.

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