Physiology 3140A Lecture Notes - Lecture 8: Ldl Receptor, Golgi Apparatus, Adipose Tissue

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Physiology 3140 Lecture 8
Lipid Transport
September 25 2017
Lipid Transport
- Absorption is not straight forward through our intestinal tract
- Proper absorption requires emulsification (bile action)
- Transport in body requires transport vehicles
Dietary Lipid Absorption
- Bile salts in the liver coat fat droplets and emulsify it
o Half water soluble, half insert themselves into the lipid
- Through emulsion large fat droplets become smaller
- Pancreatic lipase and colipase break down fats into monoglycerides and fatty acids stores in micelles
o Micelles are smaller versions of emulsified fat droplet
- Bile salts get recycled use them over and over
- Monoglycercides and fatty acids move out of micelles and enter cells by diffusion (they are small,
they can get across the PM)
- Cholesterol has to be transported into the cell
- Cell takes these components, puts them together into proteins in the smooth ER, then the golgi
apparatus and packages them into chylomicrons
o Chylomicrons: cholesterol + triglyceride + protein
- Chylomicrons secreted by Golgi apparatus and removed by the lymphatic system NOT capillaries
o Because the distance between cells in capillaries are TOO small
o Chylomicrons are too large can not squeeze their way through the cell to cell contacts in
capillaries
o Go to the lacteals part of the lymphatic system
It is more loose
Bile
salts
Bile salts
recycle
Bile salts from
liver coat fat
droplets.
Micelles
Emulsion
Large fat
droplets from
stomach Pancreatic lipase
and colipase break
down fats into
monoglycerides
and fatty acids
stored in micelles.
Lumen of small intestine Cells of small intestine
Monoglycerides and fatty
acids move out of micelles
and enter cells by diffusion.
Cholesterol is
transported
into cells.
Absorbed fats combine
with cholesterol and
proteins in the intestinal
cells to form chylomicrons.
Cholesterol + triglycerides + protein
Chylomicron
Golgi
apparatus
Smooth
ER
Chylomicrons are
removed by the
lymphatic system. Capillary
Lacteal Lymph to
vena cava
Interstitial fluid
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Lipoprotein Structure
- Lipoprotein:
o Phospholipids
Head = hydrophilic
Tail = hydrophobic
o Triglycerides
o Cholesterol
o Apolipoprotein
- This is what the gut secretes into the lacteals in the lymph
which gets into the blood stream
o Gets to fat and binds adipose tissue
o Adipose tissue sucks out the triglycerides and free
fatty acids
o Now these are remnants and picked up by the liver
and repackaged
Lipid Transport Post-Absorption
- From the lacteals to the blood stream, lipids travel in chylomicrons throughout the body
- Adipose cells can extract lipids using lipoprotein lipases
- Chylomicrons remnants (empty) are metabolized by the liver
- Excess cholesterol and triglycerides can be stored in the liver
- Liver can also send lipids to the rest of the body in water-soluble carriers
- Adipose can send lipids to the liver in similar carriers
Types of Lipoproteins
- Intestine has chylomicrons
- First goes to fat and the fat grabs triglycerides
- The chylomicron remnants go to liver and repackages the fat + protein into VLDL and LDL
o Fewer triglycerides in VLDL (very low density lipoprotein)!
o LDL (low density lipoprotein) has more cholesterol and phospholipid, decreasing the
amount of triglycercides
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- After it is sent out to fat and different cells in our body, it goes back to our level as HDL (high density
lipoprotein)
o Little cholesterol, some fat and phospholipid, A LOT of protein
- Need to increase HDL, decrease LDL (has more fat, cholesterol, phospholipid)
Internalization of LDL
- Occurs through the process of endocytosis
- Ligands binds to receptor
- Apolipoprotein in the lipoprotein is what LDL receptor binds to at the cell surface
o Whole structure will bind to the LDL receptor via the apolipoprotein
- Receptor migrates to clathrin coated pits
- Internalization / endocytosis occurs
- Clathrin is a triskelion
o Causes deformation, invagination of cell surface bilayer
o 3 peptides make this protein, coming together with different clathrin molecules
o Puling the membrane in with it
o Proteins (dynamin GTPase) wrap themselves around the neck and pinch it off in twisting
motion
- Now that you have made the vesicle, the clathrin coat is no longer needed; it falls off
- Clathrin molecules go back to the membrane to get recycled
- pH inside endosome is low
o The receptor and ligands separate at low pH
- Ligands go to lysosome or Golgi for processing
- Receptors go back to the plasma membrane to be recycled
o Fuse with the PM
o Continuously use the same receptor over and over again
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