Topic 13: Lipid Digestion, Absorption and Trafficking Flashcards
What is it about Bile Acids/Salts that help with lipid digestion?
Bile Salts act as detergents, emulsifying lipids. This allows the lipases to access and digest the lipids.
Lipases can only act on the surface (lipid-water interface) of a lipid.
Increases surface area for lipase action.
What are Bile acids derived from?
Cholesterol
What does their structure look like?
Cholesterol (3 bedrooms and a bath…)
What are the PRIMARY Bile Acids?
Cholic Acid and Chenodeoxycholic Acid
What are the SECONDARY Bile Acids?
Cholic –> Deoxycholic Acid
Chenodeoxycholic –> Lithocholic Acid
Which Bile Acid is the one least able to be reabsorbed and lost in the feces?
Lithocholic Acid
What AAs are bile acids conjugated with?
Glycine and Taurine
What does conjugation do to Bile Acids?
Increase Solubility
Why is Taurine essential for kitties?
They favor making Taurine conjugated Bile Acids
What else is secreted with Bile Acids/Salts?
Water, Cholesterol, Phosphatidyl Choline (lecithin), Bilirubin, and Bile
From the liver, where does bile go?
Liver –> Common Bile Duct –> Duodenum
If you don’t need Bile it will back up and flow through the Cystic Duct and into the Gall Bladder.
What hormone causes secretion of Bile from the Gall Bladder?
Cholecystokinin (CCK)
What is the functional unit of lipid?
Triacylglycerides/Triglycerides (TAG)
What tissues secrete lipases?
Salivary glands, Stomach, Pancreas
How do salivary/gastric lipases digest lipids?
TAG –> DAG + FFA
accounts for about 1/3 of lipase activity in adults
Work optimally at acidic pH
How do pancreatic lipases digest lipids?
TAG –> 2-MAG + 2FFA
2-MAG just means the middle FA is still attached to the glycerol backbone and the ends have been freed.
Bile Salt Dependent (BSL)
Where are Bile Acids reabsorbed and approximately how much is conserved?
Ileum – 90-99% reabsorbed (reduce, reuse, recycle)
Enterohepatic Circulation
Which Lipases are Bile Salt Dependent?
Pancreatic (BSDL)
AND
Breast Milk of primates and other animals
Important for NEONATES to aid lipid digestion.
What is enterohepatic ciruclation in reference to?
the recycling of Bile Acids/Salts
What lipase is inhibited by bile acids?
CDL: Colipase Dependent Lipase
It is allosterically activated by Colipase
What is PRPL-2?
Pancreatic Lipase Related Protein.
It is Colipase dependent just as CDL is.
Hydrolyzes TAG, phospholipids, and Galactolipids.
Important in NEONATES.
What does colipase do?
It helps Lipase BIND to the surface of emulsion droplets.
What results from lipase and bile acid action?
Mixed Micelles!
What is in a mixed micelle?
LCFA, 2-MAG, lysolecithin, cholesterol, fat soluble vitamins (A,D,E,K)
What happens to mixed micelles upon absorption into an enterocyte?
LCFA attached to CoA for activation –> Fatty Acyl-CoA
They are then either:
added to glycerol backbones (MAG or DAG) to regenerate TAGs.
added to Glycerol-3-P to generate Phosphatidic Acid (then more added to generate DAG then TAG)
added to lysolecithin to generate Lecithin
added to Cholesterol to generate Cholesterol Ester
All of which are incorporated into Chylomicrons
How are MCFA and SCFAs absorbed?
They can cross directly through an enterocyte and into hepatic portal circulation
What is in a chylomicron?
TAGs, Lecithin, Cholesterol Ester, Fat Soluble Vitamins (A,D,E,K)
AND
APO-B48
What happens to Bile Acids when mixed micelles are absorbed?
Bile Acids are left behind and reabsorbed in the distal ileum.
What is the function of APO-B48 protein in the chylomicron lipoprotein?
Export by exocytosis from enterocytes through basal membrane
What is the structure of a phospholipid?
Glycerol Core (C1,C2,C3) with FAs at C1 and C2 and a varied side group (R3) linked to C3 by a phosphate bridge.
What is the function of phospholipids?
Most abundant cell membrane component
Anchorage of cell membrane proteins and carbs
Mediators of cell signaling
How are phospholipids broken down?
Phospholipases (see slide 12 for clarification) PLA1 - cuts after O at C1 PLA2 - cuts after O at C2 PLC - cuts after first O at C3 PLD - cuts after P at C3
How are TAGs reassembled?
FA + CoA.SH via Acyl-CoA Synthetase –> Fatty Acyl-CoA
Uses ATP –> AMP + PPi (pyrophosphate – irreversible)
Fatty Acids must first be ACTIVATED by adding CoA
What is the fate of a chylomicron after entering lymphatic circulation?
Lymphatics–>Blood–>LPL digestion into target cell –> Chylomicron remnant to LIVER –> recycled into VLDL –> general circulation
Cholesterol remains after action by LPL
What is the fate of VLDLs after entering general circulation?
Blood –> LPL action to become IDLs –> IDLs can enter liver for recycling OR more LPL action to become LDLs
Cholesterol remains after action by LPL
What is the DENSITY referring to in VLDLs, IDLs, LDLs, HDLs?
Protein Density!
VLDLs have tons of fat so less dense with protein; HDLs start with very little fat so more dense with protein
What happens to LDLs once they are generated in the blood stream?
The LIVER can take them up and Recycle them
OR
Can bind to LDL Receptors, deliver CHOLESTEROL to target cells, become HDLs
What is the story with HDLs?
HDLs can be made from the LIVER or derived from LDLs after they dump their cholesterol.
HDLs can suck up cholesterol and return it to the liver as well!
What are the peripheral Apoproteins?
apoproteins A, C, and E
What are the integral Apoproteins?
APOB100 - much bigger –> for export of VLDLs from liver
APOB48 - much smaller –> for export of chylomicrons from enterocytes
APOB100 contains APOB48 and is much larger
What apoproteins are on chylomicrons?
APOB-48 - export from enterocyte
APOC-II - picked up from HDL, bind and activate LPL
APOE - binds chylomicron Remnants at liver for recycling
What apoproteins are on VLDLs?
APOB-100 - export of VLDLs from liver
APOC-II - picked up from HDL, bind and activate LPL
APOE - binds chylomicron Remnants at liver for recycling
What apoproteins are on IDLs, and LDLs?
the same as VLDLs: apoB-100, apoC-II, apo-E
What apoproteins are on HDLs?
APOA1 - interacts with ABCA1 which activates LCAT for cholesterol uptake (helps HDL suck up cholesterol)
APOA2 - helps the HDL take up cholesterol by stabilizing APOA1 structure
APOC-II and APOE for transfer to the chylomicrons and VLDLs
What is the LCAT on HDLs?
an ENZYME that put short chain “things” on the cholesterol that facilitates sucking up cholesterol from target sources
What is the target tissues for circulating Chylomicrons
Muscle, Adipose, and Mammary Glands
Where is Hormone Sensitive Lipase (HSL) found?
inside Adipose tissue
What is the function of HSL?
break down TAG in the fat cell and release FFAs to circulation
What is the main carrier of FFAs in the circulation?
ALBUMIN
What ACTIVATES HSL?
Glucagon, Catecholamines, Thyroid Hormone, Cortisol (Glucocorticoids), GH, TSH, MSH, ACTH, ADH
What DEactivates HSL?
Insulin, Ketones, PGE
What does the liver do with excess fat in times of high blood [FFA]?
same thing it always does, build it back into VLDLs and return it to target cells (muscle and adipose)
Futile Cycling
How does LCAT help take up cholesterol from target sources?
Attaches cholesterol to lecithin, making more hydrophobic, pushing it to the center of HDL
How are HDLs removed from blood by liver?
apoA-1 binds to SR-1 in LIVER and steroidogenic tissues –> recycled
Why is LDL that “BAD” cholesterol and HDL the “Good” cholesterol?
HDL removes cholesterol from the bloodstream. LDL doesn’t.
Is Hypercholesterolemia a concern in animals?
No
What is the only way the body can get rid of Cholesterol?
BILE –> FECES
