Synthesis and secretion of nascent DHL to blood.
·
It is produced mainly by liver and partly by
intestinal cells.
·
Nascent HDL is a small discoidal phospholipid bilayer
with free cholesterol, apo A, apo C and apo E.
2. Maturation of HDL in blood.
·
Nascent HDL binds with specific receptor present on
cell membrane of peripheral tissues.
·
Free cholesterol efflux from peripheral cells to
nascent HDL down the concentration gradient.
·
On coming to HDL free cholesterol is immediately converted
to cholesterol ester by lecithin cholesterol acyl transferase and thereby free
cholesterol concentration of HDL remains low to facilitate cholesterol efflux
from tissues.
·
Thus nascent HDL gradually becomes rich in CE and
converted to spherical HDL3.
3. Further modification of HDL3 & synthesis of
HDL3.
·
HDL3 continues uptake of cholesterol from
peripheral cells.
·
Subsequently HDL3 transfer part of its CE
to other circulating apo B containing lipoproteins in exchange of TAG and free
cholesterol from them. This exchange is mediated by cholesterol ester transfer
protein.
·
At this point HDL3 gets even larger and
become HDL2.
4. Clearance of mature HDL.
·
HDl2 goes to liver and binds with
hepatocytes where HDL off loads cholesterol.
·
From hepatocytes offloaded cholesterol is disposed
subsequently by three mechanisms.
o Excretion
with bile as free cholesterol
o Conversion
to bile acid and then excretion with bile
o Repackaged
into VLDL and then secretion into blood.
5. Some of the HDL2 after having their cholesterol
off loaded is subjected to hepatic lipase present in hepatic sinusoidal
endothelium. HL hydrolyzes the TAG and phospholipid of HDL2 and
converts them again into HDL3 particles. Later on these particles
join with the newly formed nascent hepatic HDL and return to plasma to
participate in the next cycle of cholesterol extraction from peripheral
tissues. This interchange of HDL2 and HDL3 is known as
HDL cycle.
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