3. ETYMOLOGY OF CHYLOMICRON
The word "chylomicron" has been derived
from two greek words:
• "Chylos“ means milky
• “Mikros" means small
• Chylomicrons= small milky (globules).
11/20/2014 3
4. DEFINITION
• A large plasma lipoprotein particle, occurring
as a droplet consisting primarily of
triglycerides and functioning in the transport
of neutral lipids from the intestine to the
tissues by way of the lymph.
11/20/2014 4
5. STRUCTURE OF CHYLOMICRONS
• Chylomicrons are considered large
lipoproteins because of lipid, phospholipid
and protein constituents.
• However, the Protein Constituents are
extremely low although their role in the
chylomicrons metabolism remains vital.
11/20/2014 5
8. SIZE OF CHYLOMICRONS
• According to Scientists, the diameter of these
particles can range from:
• 75 to 1200 nm
• 1200 nm would be largest at its production in
the intestinal cells.
11/20/2014 8
9. ORIGIN OF CHYLOMICRONS
• Chylomicrons are formed in the
endoplasmic reticulum of the mucosal
cells within the villi of the duodenum.
• Secreted through the baso-lateral
membrane into the lymphatic system.
• From the lymph to the blood systems
11/20/2014 9
10. LIFE CYCLE OF CHYLOMICRONS
Life cycle of chylomicrons consist of three
stages that differ in the constituency of
chylomicrons because some of the protein in
the form of Apolipoprotein will enter the
chylomicron particles as it reaches its
destination via the circulation.
11/20/2014 10
11. STAGES OF LIFE CYCLE
The Life Cycle of Chylomicrons can be
illustrated as having three distinct stages.
These stages include:
• The Nascent Chylomicrons
• The Mature Chylomicrons
• The Remnant Chylomicrons
11/20/2014 11
12. NASCENT CHYLOMICRONS
• initial form
• formed in the intestinal epithelial cells or
inside the enterocytes.
• released by exocytosis
• central lacteal of vessels to blood via thoracic
duct
• They contain mainly Triglycirides , Cholestrol,
Phospholipids and Apolipoprotien B-48
11/20/2014 12
13. MATURE CHYLOMICRONS
• HDL donates apolipoprotein C2 and
apolipoprotein E to the nascent chylomicron,
and convert it to into mature chylomicron.
• Apolipoprotien C2 is the co-factor for
lipoprotien lipase activity.
11/20/2014 13
14. REMNANT CHYLOMICRONS
• Once the store of triglycerides become low,the
chylomicron donates it’s Apolipoprotienc2
back to the HDL know it is called remnant
chylomicron
• much smaller in size
• Apolipoprotien B-48 and Apolipoprotien E
• break down via endocytosis
11/20/2014 14
16. TRANSPORTATION OF FATS
• CCK will travel into the blood stream reach
the galblader
• Galblader contraction cause the fat to enter
into the bile.
• The bile will the travel down through bile duct
into the duedenum .
• The bile is going to emulsify the fat turn into
small droplets so that it could be absorb.
11/20/2014 16
17. CONTINUED…..
• Enter into the enterocytes
• The fat and the cholestrol will be packed into
chylomicron.
• Released from the basal lateral site of
enterocyte.
• Chylomicron will go into the lacteal
11/20/2014 17
18. CONTINUED…..
• From lacteal it will travel into the thoracic
duct.
• The chylomicrom will enter into the
circulatory system .
• In blood stream they going to contain two
new Apo Protien :
• Apo C and Apo E
11/20/2014 18
19. Fats
Duedenum
Absorption by
Enterocytes
Enter into blood
stream
Liver Adipose tissue 11/20/2014 19
20. TRANSPORT OF FATS TO LIVER
• When chylomicron
enter into the liver
• APO-E will bind
with the LDL-R
• Chylomicron will
take up by the liver
• And triglycirides
are use by the liver
11/20/2014 20
21. TRANSPORT OF FATS TO ADIPOSE
TISSUE
• Adipose is made up of lipocytes.
• They express the emzye called lipoprotien
lipase.
• Chylomicron will bind to the lipoprotien of
lipase through apo-c
• enzyme is going to cleave the triglycirides into
indidvidual fatty acid and glycerols.
11/20/2014 21
22. CONTINUED…..
• Then they absorb into the fats cells.
• The amount of the triglycerides is low
• Chylomicron will lose the APO-C
because of the less amount of
triglycerides.
11/20/2014 22
23. TRANSPORT OF FATS TO ADIPOSE
ADEPOCYTES
OR
FAT CELL
TISSUE
11/20/2014 23
25. IMPORTANCE OF CHYLOMICRONS
• Lipid metabolism
• Fatty nutrients circulation and absorption in
the intestinal cells
• Gather proteins and cholesterols from the
lymphatic system.
• Supply triglycerides and cholesterols to
tissues
11/20/2014 25
26. CHYLOMICRON RETENTION
DISEASE
• Chylomicron retention disease is a rare
disease.
• It's an inherited disorder that affects the
absorption of dietary fats, cholesterol, and
certain fat-soluble vitamins.
• A lack of chylomicron transport causes
severely decreased absorption (malabsorption)
of dietary fats and fat-soluble vitamins.
11/20/2014 26
27. SYMPTOMS
• The signs and symptoms of chylomicron
retention disease appear in the first few
months of life.
• They can include failure to gain weight
• Failure to grow at the expected rate
• Diarrhea
11/20/2014 27
CHYLOMICRON HAS A SINGLE MONOMERE OF PHOSPHOLIPIDS AND CHOLESTROL….INSIDE THERE ARE TRIGLYCIRIDES AND THE INTERIGOPROTIEN APO B48 – IT IS NEEDED FOR CHYLOMICRON SYNTHESIS…
in the absorptive cells of the intestine, which are called and are highly efficient in absorbing and transporting the absorbed nutrients through the circulation or else through the lymphatic system. In the case of chylomicrons, once formed, the large size prevents them from entering the circulation directly and
Chylomicrons are formed in the endoplasmic reticulum in the absorptive cells of small intestines, to be specific the mucosal cells within the villi of the duodenum. Newly formed chylomicrons are secreted through the baso-lateral membrane into the lymphatic system. Chylomicrons are released from the lymph to the blood systems, and supply the tissue with fat absorbed from the diet.
This is the initial form of the chylomicrons, which are formed in the intestinal epithelial cells or inside the enterocytes. It is formed by combining triglycerides, phospholipids, cholesterol esters and an apolipoprotein known as apolipoprotein (apo) B48. Once formed, the particles are secreted into the lymphatic system (and hence the name ‘chyle’) before being carried into the circulation at the site where the major lymphatic vessel (thoracic duct) enters the subclavian vessel.
The nascent chylomicrons would further receive cholesterol particles from other apolipoproteins present in the lymph or else in the plasma. At the same time, it would receive an apolipoprotein known as ‘apo C’ from high-density lipoproteins (HDL) which will convert nascent chylomicrons into its mature forms. While nacent chylomicron is circulating in the blood, it exchanges components with high density Lipoprotien (HDL)
Following receiving apo Cs from HDL (more specifically apolipoprotein C-II) the chylomicrons will have the ability to undergo metabolism at the sites where lipoprotein lipase enzyme activity is abundant. Such sites include skeletal muscles, cardiac muscles, adipose tissues, and mammary glands. One common characteristic of all these tissues is that their high requirement for triglycerides for various needs such as energy, storage or else production of milk. CO-FACTOR FOR THE LIPOPROTIEN LIPASE ACTIVITY:AT THIS POINT THE TRIGLYCIRIDES PRESENT INSIDE THE CHYLOMICRON MUST HYDROLIZE BECOZ OF THEAPOLIPOPROTIEN C2 IS THE CO-FACTOR FOR THE LIPOPROTIEN LIPASE ACTIVITY.
When mature chylomicrons encounter the enzyme lipoprotein lipase, they will break down the triglycerides into fatty acids and monoglycerides. This will make the large triglyceride core of the chylomicrons to shrink and thus become a triglyceride depleted, cholesterol rich, and protein rich, ‘remnant chylomicrons’.
The remnant chylomicrons will exchange the excess apolipoproteins, specifically the apo Cs, with HDL and thereby return apo Cs for re-use. The remaining chylomicron particle would be metabolized in the liver via the LDL receptors and it will be aided by the presence of apo E that it received from various tissues where chylomicrons were metabolized. The clearing up process of remnant chylomicrons takes place within few hours of ingesting fatty diets and therefore is an extremely efficient system in healthy individuals. However, in some individuals, the duration for clearing up may not be so rapid and thereby would contribute to prolonged elevation of triglycerides following a meal. break down via endocytosis
once it is return back to the liver.
CCK WILL TRAVEL INTO THE BLOOD STREAM REACH THE GALBLADER AND CAUSE GALBLADER CONTRACTION WHEN THE GAL BLADER CONTRACTS IT WILL BILE.THE BILE WILL THE TRAVEL DOWN THROUGH BILE DUCT INTO THE DUEDENUM .THE BILE IS GOING TO BREAK DOWN AND EMULSIFY THE FAT TURN INTO SMALL DROPLETS SO THAT IT COULD BE ABSORB.AS IT ENTER INTO THE ENYEROCYTES THE FAT AND THE CHOLESTROL WILL PAKAGE INTO CHYLOMICRON.NOW THEY R GOING TO RELEASED FROM THE BASAL LATERAL SITE OF ENTEROCYTE.LACTEAL IS THE PART OF LYMPHATIC SYSTEM…IT WILL TRAVEL THROUGH THE LYMPHATIC SYSTEM END UP INTO THE THORACIC DUCT…THE CHYLOMICROM WILL ENTER INTO THECIRCULATORY SYSTEM .IN BLOOD STREAM THEY GOING TO CONTAIN TWO NEW APO PROTIEN…APO C AND APO E..
First we’ll discuss about the liver… when chylomicron enter into the liver….. Hepatocyte which is liver which is the the liver cell….it has therecepter called as LDL-R recepter…chylomicron will bind with LDL-R recepter using it APO-E not APO-C…the chylomicron is going to be taken up by the liver……and triglycirides are use by the liver….
ADIPOSE IS MADE UP OF LIPOCYTES…THEY EXPREE THE EMZYE CALLED LIPO[ROTIEN LIPASE…CHYLOMICRON WILL BIND TO THE LIPOPROTIEN OF LIPASE THROUGH APO-C NOT WITH APO-E…THE ENZYME IS GOING TO CLEAVE THE TRIGLYCIRIDES INTO INDIDVIDUAL FATTY ACID AND GLYCEROLS…..THEN THEY ABSORB INTO THE FATS CELLS….THE AMOUNT OF THE TRIGLYCERIDES IS LOW AFTER THIS AND IT WILL KEEP ON DECREASING…WHEN CHYLOMICRON WILL REACH ABOVE 20%THE CHYLOMICRON WILL LOSE THE APO-C AND IT WILL NOT HAVE MUCH TRIGLYCERIDE LEFT BECOZ THEY ABSORB BY THE ENZYME …..
NOW THE CHYLOMICRON IS CALLED THE CHYLOMICRON REMNANT…IT LACK APO-C ….IT WILL THEN GO INTO THE LIVER AND THEN INTO THE LIVER CELL …..IN THIS THE CHYLOMICRON REMNANT RECEPTOR IS USED INSTEAD OF LDL-R …IT WILL BIND TO THE RECEPTOR AND THE LIVER IS GOING TO TAKE UP ITS TRYGLYCERIDES for its own use….
Chylomicrons will form a particle consisting of triglycerides and cholesterol core with a surface consisted of apolipoprotein and phospholipids. This unique structure will allow fatty nutrients to enter the human circulation following its absorption in the intestinal cells.
Once the chylomicron reaches a tissue, which requires or allows its metabolism, it will free-up the triglycerides and cholesterols and would leave the tissues back into the circulation.