Lipid Digestion, Absorption, and Trafficking Flashcards
Where do lipases act?
At the lipid-water interface
Define amphiphilic
lipid and water loving
What does it mean for bile acids/salts to be amphiphilic?
Bile is an emulsifier. Bile has a detergent action allowing them to break down large lipid droplets into smaller ones
What is the advantage of biles ability to emulsify fats?
It increases the surface area of the lipid-water interface, allowing lipases more access
What compound are bile acids made from?
Cholesterol
What are the two primary types of bile made?
colic acid and chenodeoxychilic
What is bile made?
Liver
What 2 AA conjugate bile? And what is the point of conjugation?
- Glycine and Taurine (cats favor)
- To increase solubility in an aqueous environment
How does bile work?
They are amphiphilic and help to emulsify dietary lipids in the small intestines by detergent action
Which bile salt is lost in the feces?
Lithocholic
-the others enter enterohepatic circulation pathway and are mostly reabsorbed
How do salivary and gastric lipases break down TAG?
TAG –> 1,2-DAG + FFA
How do pancreatic lipases break down TAG?
TAG –> 2-MAG (via 1,2-DAG) + 2 FFA
What is BSSL? And where do you find it?
- Bile Salt Activated Lipase
- Found in breast milk. Milk has high fat content, and infants may not have fully developed digestive capability, so you are predigesting a fatty meal for them
What will you find in a mixed micelle?
LCFA, 2-MAG, Lysolecithin (aka 1,2-DAG), Cholesterol, Fat Soluble Vitamins
What is the difference between a mixed micelle and SCFA and MCFA?
Mixed micelle: digestion occurs outside the cell and transported in
SCFA and MCFA: transported across microvilli into the cell and directly to portal system
What happens to the LCFA and 2-MAG once they enter the cell?
They recombine to form a TAG
What composes Chylomicrons and why do they form?
TAG, Lecithin, Cholesterol Esters, and fat soluble Vitamins come back together because of their hydrophobic interaction and will form droplets, and APO-B gets added on
Where do chylomicrons go after forming in the cell? What do they provide?
- They get taken up by lymphatic system, NOT venous system. It goes out into interstitium until it joins in with thoracic duct and then to venous system cranial to heart. (Rupture of thoracic duct causes Chylothorax from the chylomicrons)
- They provide fuel to tissues
What enzyme breaks down (catabolizes) phospholipids? And how many types of this enzyme are there?
- Phospholipases
- There are 4
How are TAG’s reassembled?
3 Fatty acyl-CoA get attached to a glycerol backbone make TAG. Fatty acids must first by activated CoA to add them on. This step required ATP and Acyl-CoA Synthetase
Where do you find Lipoprotein Lipase? What compound does it act on? What does it release?
- On the inner surface of capillaries
- Acts on lipoproteins, of which chylomicrons are one type
- Releases FFA
What happens to the remnants of chylomicrons?
They are released back into general circulation, reach the liver, they are broken down, components are recycled, and released back into general circulation as VLDL
What are the two sources of fuel distribution throughout the body and what are their sources?
- Chlyomicrons from the gut, after a meal
- VLDL from the liver, between meals or when you don’t have a high fat diet
What happens to VLDL as they distribute their fat? And what enzyme works on them?
- They become IDL
- Lipoprotein Lipase
What happens to IDL?
- Recycled back to liver and come back as VLDL
- Continue to shrink and become LDL
As Lipoprotein Lipase breaks off fat, what happens to the protein?
Nothing! The ratio of protein:fat changes, the density increases. The protein and cholesterol remains the same
What can LDL do as they bind to cells?
Deliver cholesterol
What happens to LDL when it reaches the liver?
It is taken up, recycled, and released back as VLDL
What lipoproteins does the liver make, release, and take up?
Makes and releases : VLDL, HDL
Takes up: IDL, LDL (both of which are donstream survivors of VLDL)
What is the ratio of protein:fat of HDL and what is their job?
High ratio of protein:fat and NO cholesterol to start. They go out and suck up cholesterol, return cholesterol back to liver, can also transfer cholesterol to other cell types, like steroid generating cells in adrenal, etc.
What is a lipoprotein?
Single layer, aggregates of various lipids (cholesterol, TAG) and proteins (apoproteins) that transport lipids in the blood and lymph. What is on the surface is most charged and polar
What are apoproeins?
Binding/recognition sites
What apoproteins will you find on chlyomicrons and what is their function?
apoB-48: export CM from enterocytes
apoC-II: binds/activates lipoprotein lipase
apoE: binds CM to liver when they are IDL or LDL for endocytosis
What apoproteins will you find on VLDL (which are made by the liver) and what is their function?
apoB-100: export from liver cells, it will become LDL and be able to bind to liver and steroid making cells
apoC-II, apoE: same as for CM
What apoproteins will you find on HDL (which are made by the liver) and what is their function?
LCAT: put short chain things onto cholesterol, helps take up cholesterol into HDL (it’s technically an enzyme)
apoA1: interacts with ABCA1 which activates LCAT
apoA2: helps apoA1
apoC-11, apoE: picked up by CM and VLDL
What happens to chylomicrons once in circulation?
They pick up apoC-11 and apoE from HDL. They then travel to muscle, adipose, and mammary tissue, and bind to their capillary endothelium
What happens to the lipoprotein when it binds to the capillary endothelial surface?
It binds by apoC-11, which activates Lipoprotein Lipase, which releases FFA an MAG which are used as fuel or storage. This leaves behind protein and cholesterol rich remnants, which are transported to the liver, bind via apoE
When the lipoprotein remnants reach the liver, what receptor binds them and what happens next?
apoE binds to remnant receptor causing receptor mediated endocytosis and lysosomal degradation
Where do you find Hormone Sensitive Lipase?
INSIDE fat cells
What does HSL do?
Break off FFA from glycerol backbone of TAG
What is one of the main carrier of FFA in general circulation?
Albumin
What activates HSL?
Protein Kinase A! It’s a phosphorylation
Glucagon, Catecholamines, Thyroid Hormone, Glucocorticoids, (and GH, TSH, MSH, ACTH, ADH)
What deactivates HSL?
Insulin, PGE, Ketones
Why do ketones inhibit HS?
If ketones rise in blood, means you already had fat release, so it will slow down further release by inhibiting lipolysis
What happens to excess FFA that the liver takes up?
Assembles into TAG
Package them into VLDL and send out into blood
Released back into blood
Redelivered back to adipose
(Liver -> VLDL -> Adipose -> FFA -> back to Liver)
Rank the lipoprotein density and size
least amount of protein and largest in size, to highest in protein and smallest in size:
(low protein, large size) CM, VLDL, IDL, LDL, HDL (high protein, small size)
What type of TAG do VLDL transport?
ENDOGEOUS TAG and choelsterol to muscle and adipose (chlyomicrons carry dietary fat)
What do Lipoprotein lipase release?
FFA and MAG which are taken up by target cells
What are the fates of IDL?
- Bind to liver via apoE, uptake, degraded
- Hydrolysis by hepatic lipase releases more FFA and glycerol
Where are chylomicrons made and how are they transported?
Made in Intestines, transported via Lymphaics
Where are VLDL made and how are they transported?
Made in Liver, transported in blood (VLDL-IDL-LDL via lipoprotein lipase)
Where are HDL made and how are they transported?
Liver makes apoA-1 and apoA-2 which combines with Phospholipid (lecithin), and released into blood as HDL (NO cholesterol)
How does HDL pick up cholesterol from blood, chylomicrons, and VLDL?
LCAT on HDL attaches free cholesterol to lecithin forcing cholesterol into the middle of the glob, allowing more room for more cholesterol to be picked up
What does apoA-1 on HDL do?
It binds to target cells ABCA1 receptor to transfer the cell’s cholesterol and phospholipids
What happens as HDL fills up?
Cholesterol has increased inside, it has become less dense, and it has become larger. It will go to the liver and steroidogenic tissues and bind via SR-B1
What does SR-B1 do?
Strips out cholesterol and HDL apoproteins are released back into the blood
What happens to the excess cholesterol in the liver?
It is secreted directly into bile or first converted to bile acids
Why is by way of the feces the only way to remove excess cholesterol?
Because we lack the enzyme to break cholesterol down. We can build it up but can’t break it down
Why is LDL called the “bad” cholesterol and HDL called the “good” cholesterol?
HDL “good” because they pick cholesterol back up. Cholesterol is only contained in lipoproteins.
Is hypercholesteremia considered a health risk in animals as it is in humans?
No, animals can have hyper, but not have clinical effects of it the same was as humans do
How does the body get rid of cholesterol (and cholesterol derivatives such as steroid hormones)?
Unrecovered bile in the feces
