LDL and VLDL Metabolism: Lipoprotein metabolism: Endogenous pathway of lipid transport

Published by Darron Toy on

Hi, this is Dr. Vijay. Today we are going to study LDL and VLDL metabolism. So, this LDL and VLDL metabolism is the transport
of lipids between liver and extrahepatic tissues and this pathway is also known as the endogenous
pathway. Perhaps liver has the capacity to synthesize
various lipids and they are packaged in the form of VLDL and later this VLDL converted
to LDL and most of this LDL hand over to extrahepatic tissues. Unlike carbohydrates and proteins, these lipids
are not water-soluble, they are water-immiscible. So, this problem is solved by mixing of these
lipids with apoproteins. So, the apolipoproteins or apoproteins act
as a carrier molecule or vehicle for the transport of lipids between different organs, in this
case between liver and extrahepatic tissues. So, here we have a liver. Our liver has got the capacity to synthesize
fatty acids. So, this partway is called de novo biosynthesis
of fatty acid. As the liver synthesizes fatty acids, 3 fatty
acids combine with glycerol. So, it could be released from the hydrolysis
of triglycerides or it can be acquired from the circulatory hydrolysis of lipoproteins
by lipoprotein lipase. Now the 3 fatty acids combine with this glycerol
to give triacylglycerol or triglyceride. So, in the liver, whatever fatty acids are
synthesized, they are converted to triacylglycerol or triglyceride. Similarly, the two fatty acids combine with
phosphoric acid and glycerol backbone and choline to give phospholipids. So, within the liver triglycerides and phospholipids
are generated and liver cell or hepatocyte has got the capacity to synthesize cholesterol
and also these cholesterol can be generated from the chylomicron remnants which are derived
from the exogenous pathway, they can be hydrolysed to give, the cholesterol ester can be hydrolyzed
to give free cholesterol and fatty acid. Now, this cholesterol or free cholesterol
can combine with one fatty acid or esterified with one fatty acid to give cholesterol ester. So, we have the different types of lipids
within the liver and remember, the majority of these lipids are endogenously synthesized
or synthesized within the hepatocytes or within the liver. Besides these lipids, the liver also has got
the capacity to synthesize some of the apoproteins like apoprotein E, apoprotein C, and apoprotein
B-100. These apoproteins play a major role in the
transport of lipids from the liver to the extrahepatic tissues through circulation. Now we have lipids and apoproteins within
the liver and all these are packaged in the form of VLDL and released to the circulation. Now here I have a liver and the extrahepatic
tissue. The metabolism of VLDL and LDL between the
liver and between the adipose tissue or extrahepatic tissues. Now the endogenously synthesized lipids are
packaged and released to the circulation in the form of nascent VLDL. So, this newly synthesized VLDL is called
nascent and VLDL and the major apolipoprotein is apo B-100 and also it contains a small
amount of apo C and apo E. Once this nascent VLDL approaches circulation or present in
the circulation it acquires some of the apo E and apo C-II from the calculating HDL and
also we studied in HDL metabolism this nascent VLDL acquires some more cholesterol esters
from the HDL and it handovers some amount of its triglycerides to circulating HDL. This is mainly by a protein called cholesterol
ester transfer protein. This we already studied in reverse cholesterol
transport mechanisms or HDL metabolism. Now after acquiring some or apo C and E and
more cholesterol esters, this nascent VLDL becomes mature VLDL. Now this apo C-II, which is present on the
surface of this mature VLDL activates the lipoprotein lipase enzyme, which is present
on the walls of capillaries or blood vessels. So, once this lipoprotein lipase is activated,
it acts on the triglycerides present on the central dense core of this mature VLDL. So it starts hydrolyzing fatty acids from
the triglyceride one by one in this way it hydrolyzes a lot of triglycerides and it handovers
glycerol backbone to the liver through the circulation., so now more and more triglycerides
or hydrolyzed more and more fatty acids are deposited in the extrahepatic tissue, through
the circulation. So, in this way, this mature VLDL becomes
small, because more and more triglycerides are hydrolyzed by lipoprotein lipase. So, this mature VLDL becomes IDL or intermediary
density lipoprotein. You can see the size of this mature VLDL and
IDL, it is small because some amount of triglycerides are hydrolyzed by lipoprotein lipase. Now this intermediary density lipoprotein,
further it moves in the circulation, again in the wall of the capillaries, the lipoprotein
lipase activated by apo C-II present in the intermediary density lipoprotein and this
activated lipoprotein lipase starts hydrolyzing more and more triglycerides present in the
central dense core of this IDL and this formation of IDL is transient in nature, it is a very
fast. This intermediary density lipoprotein further
becomes small because major amount of triglycerides are hydrolyzed by lipoprotein lipase and glycerol
will be hand over to the liver. So, this IDL becomes smaller and it is rich
with the cholesterol esters. Now this lipoprotein handovers its apo E to
circulating HDL and also apo C-II to the circulating HDL and this molecule is called LDL. Please appreciate the size of the mature VLDL,
IDL and LDL, so LDL is the smaller when compare to VLDL and IDL and the amount of triglycerides
goes on decreasing from VLDL to IDL and from IDL to LDL and this LDL is cholesterol ester
rich lipoprotein and it has got only one apolipoprotein that is apo B-100. Now, what is the fate of this LDL? This LDL, the majority of this LDL taken to
extrahepatic tissues through receptor-mediated endocytosis. There is a receptor on the surface of the
extrahepatic cell. This receptor is called LDL receptor. Remember 70 to 75% of cholesterol ester rich
LDL taken 2 extrahepatic tissue through this LDL receptor. Remaining 25 to 30% of is LDL taken to liver
through LDL receptor, that is receptor-mediated endocytosis. So, whatever endogenously derived lipids,
they are packaged and released as nascent VLDL then it acquires some amount of apo E
and apo C-II from the HDL and also it acquire some more amount of cholesterol esters from
the calculating HDL and lipoprotein lipase hydrolyses some amount of triglycerides it
will become IDL, further hydrolysis of triglycerides by lipoprotein lipase and it will be converted
to LDL, after hand overring its apo E and apo C-II to circulatory HDL. So, this LDL which is formed from the VLDL
or IDL taken to extrahepatic tissue through LDL receptors, small amount about 25 to 30%
will be uptake by liver through again LDL receptor. This LDL receptor mainly recognise by apo
B-100. So, the apo B- 100 acts as a ligand. So, because IDL also contains apo B-100, even
this IDL can be taken through this LDL receptor but major portion is LDL. You need to remember the metabolism of VLDL
or LDL is mainly the endogenous pathway or endogenously derived lipids, no doubts there
are some of the lipid are derived from chylomicron remnants which are taken to the liver through
LRP from the dietary lipids but major bulk lipids are lipids synthesized within the liver
and release to the circulation as VLDL. This is with respect to LDL metabolism or
VLDL metabolism or intrinsic pathway or endogenous pathway. If you haven’t subscribed, please subscribe
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