HDL Metabolism: Reverse cholesterol transport

HDL Metabolism: Reverse cholesterol transport


Hi, this is Dr. Vijay. Today we are going to study high density lipoprotein
metabolism or HDL metabolism. So, before watching this video, you should
know some of the basics, for that please watch this video, that is under lipid chemistry
playlist where I have explained basics about lipoproteins, like what are the different
classes of lipoproteins, what is the composition and apoproteins types and their site of synthesis,
after watching this video, watch HDL metabolism video. If you haven’t subscribed, please subscribe
this channel and press the bell icon for future notification. First, we will see how this HDL is synthesized. So, whenever the HDL is synthesized, we call
it as nascent HDL and synthesis of this HDL requires both liver as well as small intestine,
that is intestinal mucosal cells. The nascent HDL as mentioned in Harper’s textbook
of biochemistry, it is discoid shape and also they have mentioned, it is phospholipid lipid
bilayer but strictly speaking it is not a bilayer because it is a monolayer of phospholipid
but the major composition of this nascent HDL is phospholipid, you can see there are
monolayer of phospholipids and free cholesterol. You can say, there is almost nil cholesterol
ester or triglycerides in nascent HDL. As you know, the nascent HDL contains a apoprotein
it is called apolipoprotein AI. It is the major apoprotein of high-density
lipoprotein and it plays a pivotal role in HDL metabolism. Among all apoproteins present in the HDL apoprotein
AI accounts for 70% of apoproteins proteins present in the HDL. Apart from this, the nascent HDL, when it
is released into the circulation, it acquires apolipoprotein C and apolipoprotein E from
the liver through the circulation. As it is synthesized beginning, it has got
apolipoprotein AI, it is the major apolipoprotein of HDL and when it reaches the circulation
it acquires apolipoprotein C, is mainly C-II and apolipoprotein E which are synthesized
from the liver. So, this nascent HDL acquires an important
enzyme in HDL metabolism from the liver through the circulation and the name of that enzyme
is LCAT, again this enzyme plays a very important role in reverse cholesterol transport mechanism. Function of HDL, we say HDL is a good cholesterol
becaus it removes the cholesterol from the peripheral tissue and hand over to liver and
in the liver, it can be metabolized to bile and excreted or secreted to the intestine. So, before going to HDL metabolism, you should
know something about the enzyme LCAT. The full form of LCAT is Lecithin Cholesterol
Acyl Transferase. Here we have a lecithin. So, the major action of LCAT is, it acts on
lecithin. You can see here, this is a glycerol backbone,
here we have a fatty acid and in the second carbon atom of glycerol also there is another
fatty acid, whereas 3rd carbon atom of the glycerol backbone esterified with the phosphoric
acid and choline. So, it is lecithin nothing but phosphatidyl
choline or phospholipid. Now the action of this LCAT, it removes fatty
acid attached to 2nd carbon atom of glycerol backbone and handovers this fatty acid to
the cholesterol, the 3rd carbon atom or hydroxyl group attached to the 3rd carbon atom of the
cholesterol catalyzed by LCAT. So, you can see, as the name suggest Lecithin
Cholesterol Acyl, acyl means fatty acid, transferase. So, LCAT is transferring this acyl group from
the lecithin to the cholesterol, now cholesterol will become cholesterol ester. You can see the R2 or fatty acid which is
attached to 2nd carbon atom of the glycerol backbone, now is esterified with the 3rd carbon
atom of the cholesterol that is esterified with the hydroxyl group of the cholesterol
in turn this free cholesterol become cholesterol ester. So, this lecithin now without the fatty acid
it will become lysolecithin. So, this is very important enzyme in HDL metabolism
and a apolipoprotein A-I which is present in the HDL stimulates this LCAT. So apo A-I is activator of LCAT. Now we see the metabolism of HDL. We have nascent HDL, which has got apo A-I,
LCAT, apo C and apo E. So, the synthesis of this HDL requires ilver as well as intestinal
mucosal cell. Now the function of HDL, it removes cholesterol,
these are all cholesterols from extrahepatic tissue or very peripheral tissue and hand
over this cholesterol to the liver. We don’t want any cholesterol accumulation
in the peripheral tissue, that might lead to atherosclerosis and cardiovascular disease
or cerebral vascular accident. Now this nascent HDL, through the circulation,
it comes near the extrahepatic tissues, as the nascent HDL approaches extrahepatic tissue,
in the extrahepatic tissue or cell membrane of extrahepatic tissues, there are 2 types
of transporters. The first type of transporter is called ATP
binding cassette transporter A1, simply we can abbreviate it as ABCA1. This transporter present in the cell membrane
of peripheral tissues or extrahepatic tissues. The another type of transporter is called
scavenger receptor B1, they belong to class B scavenger receptor family and with the help
of these 2 transporters, this nascent HDL acquires the cholesterol present in the extrahepatic
tissue, because we don’t want this cholesterol accumulation in the extrahepatic tissue, it
might lead to atherosclerosis. Now you can see, through these transporters
the cholesterol approaching to the nascent HDL, either through ABCA1 or through scavenger
receptor B1. Now once the free cholesterol is coming in
contact with the nascent HDL, through these 2 transporters, the LCAT is activated by apo
A-I. The apo A-I apoprotein activates this enzyme,
Lecithin Cholesterol Acyl Transferase. So, we know that this phospholipid which are
present on the periphery of nascent HDL, they are, majority of them are lecithin or phosphatidylcholine. Now once is LCAT is activated lecithin converted
to lysolecithin and this free cholesterol will become cholesterol ester. You can see, now fatty acid is esterified
with the cholesterol. Now the cholesterol become cholesterol ester. This free cholesterol will become now cholesterol
ester. Please note here the free cholesterol converted
to cholesterol ester with the help of LCAT. Now once free cholesterol is converted to
cholesterol ester, it will migrate to the interior of the nascent HDL because it is
hydrophobic, only free cholesterols occupies periphery of the lipoprotein. So, when they become cholesterol esters they
will migrate to the inner core or central core of the lipoprotein, here in this case,
it is nascent HDL. So, like this through this ABCA1 and SRB-1,
whatever cholesterols, free cholesterols, they are effluxed into the nascent HDL and
they will go interior or central core of the nascent HDL and now this nascent HDL will
become spherical in shape. Initially it is discord in shape, now because
of migration of these cholesterol esters, because they’re hydrophobic, so this discoidal
nascent HDL will become now spherical HDL. This HDL is called HDL 2. Once there is formation of HDL 2, it will
hand over some of its cholesterol esters to VLDL. You can see this is a VLDL. VLDL contains triglycerides and cholesterol
esters in the central dense core. Now this HDL 2, it will hand over some of
its cholesterol esters to the VLDL and in exchange it will receive some of the triglycerides. Now this HDL 2 will become HDL 3. This exchange is mainly by a protein called
cholesterol ester transfer protein, CETP. The function of cholesterol ester transfer
protein is exchange of cholesterol esters and triglycerides between HDL 2 and VLDL. So, now this HDL or HDL 3 is called mature
HDL. Now this HDL taken to liver through a receptor,
again it is the same receptor scavenger receptor B1. So, scavenger receptor B1 has got duel role. So, it helps in a efflux of the cholesterol
from the extrahepatic tissue to the nascent HDL as well as intake of this HDL, that is
mature HDL from the circulation to the liver. So, this receptor also called HDL receptor. So, by this way HDL helps in reverse, so this
cholesterol, we don’t want this cholesterol accumulated in the peripheral tissue or extra
tissue. So, that is why, the HDL is called good cholesterol
and the mechanism is called reverse cholesterol transport. So, once cholesterols are transported from
the peripheral tissue to the liver, in the liver we know that it can be converted to
bile and released in to the intestine. This is actually the metabolism of HDL. You should remember the initial HDL which
is synthesized with the help of small intestinal mucosal cells and liver. it is called nascent HDL and it is, you can
say almost devoid of cholesterol ester and triglycerides, it is mainly made up of phospholipids
and free cholesterol and the major apolipoprotein A-I, apo A-I and it has got an important enzyme
LCAT. Apart from this, it receives two apolipoproteins,
C and E from the liver. It acquires excess cholesterol deposited in
the peripheral tissues through these 2receptors; ABCA1 and SR-B1. Once they acquire free cholesterol the LCAT
esterifies this free cholesterol to cholesterol ester and it will be migrated to inner core
of the nascent HDL and HDL will become spherical in shape, it is called HDL 2 and some of cholesterol
esters, it hand overs to VLDL in exchange with triglycerides with the help of CETP,
cholesterol ester transfer protein. Now this will become HDL 3 and this HDL 3
is taken to the liver with the help of HDL receptor or scavenger receptor B1. This is HDL metabolism. Thanks for watching.

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