Lipoprotein I and II

Question 1

describe electrophoretic separation of lipoproteins

Answer 1

• HDL, LDL and IDL have different apolipoproteins pattersn which allows the separation by electrophoresis
• chylomicrons contain only <2% apolipoproteins and stay at the “origin” of the electrophoretic separation

Question 2

describe the assembly of chylomicrons

Answer 2

• intestinal mucosal cells form chylomicrons and use phospholipids, CEs and TAGs
• assembly of apo B-48 with lipids needs the microsomal TAG transfer protein (MTP)
• both apo B-48 and MTP are needed for the release of chylomicrons into the lymph

Question 3

describe the modification of nascent chylomicrons

Answer 3

• in the blood, nascent chylomicrons are modified to chylomicrons by HDLs that transfer apo E and apo E
  
  • apo C-II activates LPL
  • apo E allows hepatic uptake of chylomicron remnants

Question 4

describe the function and location of lipoprotein lipase (LPL)

Answer 4

• LPL cleaves TAGs of lipoproteins
• LPL is anchored within capillaries of heart, skeletal muscle and fat tissue and acts in the blood
• LPL needs activation by apo C-II

Question 5

describe the regulation of LPL activity

Answer 5

• Cardiac LPL activity is insulin-independent
  
  • the heart always takes up FAs for its energy metabolism
• adipocyte LPL activity is insulin-dependent
  
  • when CMs and VLDL are abundant then the generates FAs are taken up into fat cells and stored as TAGs

Question 6

describe the formation of CM remnants

Answer 6

• CMs are the lipoproteins with the highest % of TAGs
  
  • after TAG cleavage by LPL, CM remnants are formed which are smaller and denser
• CM remnant contains apo E and apo B-48 since apo C is returned to HDL
• CM remnants are taken up only into the liver
  
  • the endocytosis uses a remnant receptor that recognizes apo E

Question 7

describe the formation of VLDL and nascent VLDL

Answer 7

• VLDLs are formed in hepatocytes and contain endogenous lipids
• the nascent VLDL contains only apo B-100
  
  • HDL adds apo C and apo E resulting in functional VLDL

Question 8

describe the purpose of VLDL

Answer 8

• one purpose is to prevent TAG accumulation in hepatocytes and also provides substrates for LPL resulting in FAs for other cells
• another purpose of VLDL release is to generate eventually LDL which can distribute CEs to the cells that require it

Question 9

describe the formation of IDL and then LDL

Answer 9

• after cleavage of some TAGs by LPL, VLDL becomes IDL
• IDL acts as a substrate for hepatic lipase (hepatic TAG lipase, HTGL) which will form LDL in the blood of hepatic capillaries

Question 10

describe the formation of oxLDLs

Answer 10

• oxLDLs accumulate and enter macrophages via the scavenger receptor SR-A
• this leads to foam cells and plaque formation in an arterial wall

Question 11

describe the function of HDL

Answer 11

• the discoidal HDL is filled with CEs which are formed in the blood by the enzyme LCAT
• HDL-3 is changed to the larger HDL-2 which is connected via CETP to VLDL
  
  • some CE are taken up into VLDL
• HDL-2 binds to the hepatic SR-B1 and CEs are taken up into the liver
• the smaller HDL-3 is formed which continues being filled with CEs

Question 12

describe the function of LCAT

Answer 12

• LCAT forms cholesteryl esters in the blood which will then enter HDL to transport to the liver
• ABC-cholesterol transporters provide free cholesterol
• LCAT requires the activation of apo A-1 bound in the membrane of HDL
  
  • HDL is recognized by apo A-1

Question 13