Chylomicron metabolism: Metabolism of dietary lipids : Exogenous pathway of lipid transport

Chylomicron metabolism:  Metabolism of dietary lipids :  Exogenous pathway of lipid transport


Hi, this is Dr. Vijay. In this video, we’re going to study chylomicron
metabolism. Before going to this chylomicron metabolism,
I highly recommend to watch these 2 videos, in order to understand basics. First under lipid chemistry, you can watch
lipoproteins where we can understand different classes of lipoproteins and the’re general
structures and today in this video we’re going to study about chylomicron metabolism. So, in order to understand how chylomicron
is formed, so you need to watch digestion and absorption of lipids under digestion and
absorption playlist, where I have explained, after digestion how this chylomicron is formed
in the intestinal mucosal cell. If you haven’t subscribed, please subscribe
to this channel and press the bell icon for future notification. So, the chylomicron metabolism, we know that
chylomicron is synthesized from the intestinal mucosal cell after dietary lipids are digested
and absorbed into the intestinal mucosa cell where they produce chylomicron and it will
be released into the lymphatics and through thoracic duct, it will reach circulation. Now, this chylomicron, which is present in
the circulation, which is synthesized by small intestinal mucosal cells and the major apolipoprotein
present in the chylomicron is B-48. Apoprotein B-48 is the major apolipoprotein
present in the chylomicron because the site of synthesis of B-48 is in the intestinal
mucosal cell. As I mentioned earlier, the metabolism of
chylomicron means, it is the metabolism of dietary lipids after digestion and absorption,
because after digestion and absorption of lipids, dietary lipids are converted to chylomicron
in the intestinal mucosa cell and this pathway is also known as an extrinsic pathway or exogenous
pathway. The chylomicron which is synthesized by intestinal
mucosal cells is called nascent chylomicron. The newly synthesized chylomicron from the
intestinal mucosal cell and released to lymphatics, thoracic duct and the circulation then it
is called nascent chylomicron where it has got apolipoprotein B-48 and a small amount
of apolipoprotein A. So, when it is synthesized from the intestinal mucosal cell, it has got
apolipoprotein A-I, because A-I is synthesized from the intestinal mucosal cell and liver. Other A subtypes are acquired from the liver
through the circulation and once this nascent chylomicron present in the circulation it
acquires 2 apolipoproteins from the HDL. They are apolipoprotein E and apolipoprotein
C-II. It acquires C-I, C-II, C-III but here I have
mentioned C-II, because it plays a very important role in chylomicron metabolism. So, these 2 apoproteins received from the
HDL through the circulation, which are originally synthesized by the liver. Now, this nascent chylomicron is called mature
chylomicron. So, once it acquires apolipoprotein C-II there
is an enzyme called lipoprotein lipase, again this is a very important enzyme. It is an isoenzyme of lipase. This enzyme usually presents in the walls
of blood vessels or capillaries attached to the endothelial layer of the capillaries held
by proteoglycans of heparin sulfate. Before going further, in order to study chylomicron
metabolism, we need to know something about this enzyme because lipoprotein lipase plays
a major role in chylomicron metabolism. So, after studying about this enzyme then
we will move on to further fate of this chylomicron. This apolipoprotein C-II, which is acquired
by this nascent chylomicron through the circulating HDL, activates lipoprotein lipase. Remember lipoprotein lipase present in the
walls of the blood vessels but it is in inactive form. When this mature chylomicron, that is when
it acquires apo C-II from the HDL, it stimulates or activates this enzyme, lipoprotein lipase. So, we will see the action of lipoprotein
lipase. Here I have triacylglycerol OK, so the dietary
lipids, 80 to 90% of our dietary lipid is comprising of triglycerides and even the major
component of chylomicron is triacylglycerols or triglycerides. As we know triglyceride means tri means 3,
acyl means fatty acid, so it has got 3 fatty acids: fatty acids 1, 2 and 3 attached to
a glycerol backbone. So, this is our triglyceride. Remember 80 to 85% of dietary lipid is triglyceride. So, when we say the metabolism of chylomicron
indirectly, we are talking about the metabolism of triglycerides because it is the major component
of chylomicron. This triglyceride present in the chylomicron
hydrolyzed or catabolized or metabolized by an important enzyme lipoprotein lipase which
is present in the walls of the blood vessels. This lipoprotein lipase is activated by apolipoprotein
C-II, which is acquired by nascent chylomicron through the circulating HDL. So, this apo C-II is an activator of lipoprotein
lipase. Once lipoprotein lipase is activated it will
start hydrolyzing these triglycerides present in the central dense core of chylomicron but
this lipoprotein lipase has got specificity to cleave fatty acids attached to carbon number
one of the glycerol and the carbon number 3 or fatty acid attached to 3rd carbon atom
of the glycerol backbone. So, initially, it will cleave fatty acid one
by one attached to carbon number 1 and carbon number 3. So, lipoprotein lipase removes one fatty acid
at a time, initially, it removes fatty acid attached to the carbon number one of the glycerol
backbone. Again, it can cleave fatty acid attached to
the 3rd carbon atom of the glycerol backbone. Now this lipoprotein lipase cannot cleave
fatty acid attached to the second carbon atom of the glycerol backbone, but there is an
enzyme called isomerase, it can change the position of fatty acid attached to carbon
number two of glycerol to either to the 1st carbon atom of glycerol or to the 3rd carbon
atom of the glycerol. So. now fatty acid is again attached to carbon
number one of the glycerol so that now this lipoprotein lipase can cleave or break this
fatty acid. Now by the action of lipoprotein lipase, we
have 3 fatty acids and this triglyceride will become glycerol OK. You need to understand that, the action of
lipoprotein lipase which is present in the walls of the capillaries. So, with this knowledge, we will study the
further fate of chylomicron. Now this apolipoprotein C-II activates lipoprotein
lipase as we studied just now this activated lipoprotein lipase acts on the triglycerides
which are present in the central dense core of chylomicron because the majority of lipids
in chylomicron is triglycerides. So, we start hydrolyzing the triglycerides
as we studied this lipoprotein lipase removes fatty acids from the triglycerides by hydrolysis
of triglycerides. So, it will start removing fatty acid one
by one and the glycerol will be taken to the liver where it can be used for the synthesis
of triglycerides or gluconeogenesis. Now, these fatty acids which are hydrolyzed
by lipoprotein lipase are taken to adipose tissue or extrahepatic tissue or peripheral
tissues. So, by this way, our lipoprotein lipase hydrolyzes
a lot of triglycerides present inside the inner core of chylomicron. Now our chylomicron will become small. Please appreciate the size of the chylomicron,
that is mature chylomicron and this chylomicron, size reduced because by the action of lipoprotein
lipase. So, here initially it is 80 to 90% of chylomicron
is triglycerides, now about 40 to 50% of triglycerides are hydrolyzed by the action of lipoprotein
lipase. Now we have a smaller chylomicron and this
chylomicron handovers apolipoprotein A to the circulatory HDL. So. the HDL plays a very important role because
it acts as a repository for apolipoproteins. Even apolipoprotein C-II also received by
circulating HDL from the chylomicron. Now, this chylomicron is called chylomicron
remnant because about 40 to 50% of triglycerides present in the mature chylomicron are hydrolyzed
and size is reduced to this much size and this chylomicron which is present in the circulation
is called chylomicron remnant. What is the fate of this chylomicron remnant? This chylomicron remnant taken by the liver
by a process called receptor-mediated endocytosis that means in the liver there is a specific
receptor to internalize or for the endocytosis of this chylomicron remnant. Remember this receptor is recognized by apolipoprotein
present on the surface of chylomicron remnant. The name of this receptor is called LRP, the
full form of LRP is LDL receptor-related protein, it belongs to the LDL receptor family and
its structure is almost similar to the LDL receptor, it recognizes apolipoprotein E & B-48. The majority of chylomicron remnants are taken
to the liver through this LRP or LDL receptor-related protein, but a smaller amount of chylomicron
remnants could be taken by this receptor, which is mainly a receptor for LDL or low-density
lipoprotein. Even this LDL receptor can take this chylomicron
remnant through receptor-mediated endocytosis. LDL receptor mainly recognizes B-100 present
in the LDL but since B-100 and B-48 belong to the same family of apolipoproteins but
their site of synthesis is different, and it can recognize apo E also. By this way whatever dietary lipids are finally
taken to the liver where it could be further metabolized by hepatic lipase and cholesterol
esterase. So, the summary, chylomicron is a lipoprotein
that is synthesized from the intestinal mucosal cell after digestion of dietary lipids and
this chylomicron released into the lymphatics, then to the thoracic duct, then it will reach
circulation where it acquires apolipoprotein E and C from circulating HDL. Once it acquires apolipoprotein C-II, it will
activate lipoprotein lipase present on the walls of capillaries and once it is activated
it can hydrolyze about 40 to 50% of triglycerides present inside the central dense core of chylomicron
and the fatty acids are deposited in the adipose tissue or extrahepatic tissue or peripheral
tissue. So, now the remaining part of chylomicron
is called chylomicron remnant, after handover apo A and apo C to the circulating HDL. This chylomicron remnant taken to the liver
or uptake by the liver through 2 receptor family that is LRP and LDL receptor. This is with respect to the metabolism of
chylomicron or exogenous pathway or extrinsic pathway or in other words metabolism of dietary
lipids. Thanks for watching it.

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