BIOC Lecture 10: Lipid Transport Flashcards
What are endogenous lipids?
lipids that are naturally synthesized within the body
Where are most TAG’s made?
In the liver
What are the two ways to make TAG’s?
- From the degradation of fatty acids
- Derive from a 3C molecule in the glycolysis pathway
These two ways make glycerol 3-phosphate backbone
What needs to be removed to make a TAG?
Phosphate
What is the structure of cholesterol?
4 sterol ring structure with a hydrocarbon tail
What is every carbon molecule in cholesterol derived from?
Acetyl CoA (it is the building block)
What is cholesterol most commonly found in the form of?
Cholesterol ester for storage
How is a cholesterol ester made?
Fatty acid added to hydroxyl group
Where does cholesterol come from?
Meat and animal products such as dairy - not plants
How are cholesterol levels regulated?
The body shuts down its own cholesterol synthesis pathway when levels are high from the diet
How does the body shut down its cholesterol synthesis pathway?
By cholesterol feeding back to inhibit the enzyme HMG CoA reductase
How does the cholesterol synthesis pathway work?
- Acetyl CoA (from FFA’s, AA’s and glucose) gets converted into HMG CoA
- HMG CoA is converted into mevalonate, catalysed by the enzyme HMG CoA reductase
Is cholesterol soluble?
Very insoluble
What tissues have the greatest demand for cholesterol?
Liver and reproductive tissues
What is the only way to get rid of cholesterol?
Steroid ring cannot be degraded - excreted as bile
What is cholesterol a major component of?
Membranes and lipoproteins
What are cholesterol precursors to?
- Steroid hormones
- Bile acids
- Vitamin D
What is cholesterol important for the transport of?
Fat soluble vitamins
Why are cholesterol important for neuronal function?
Part of the myelin sheet that insulates our nerves
What are plasma lipoproteins?
particles that transport lipids, including cholesterol and triglycerides, through the bloodstream
What is the structure of plasma lipoproteins?
- Single phospholipid layer
- Polar heads point outwards
- Apolipoproteins embedded in phospholipid layer
- Packaged in the middle are hydrophobic lipids (cholesterol esters and TAG’s)
What are the 4 main lipoprotein classes?
- Chylomicrons
- VLDL
- LDL
- HDL
Which lipoproteins are TAG rich?
Chylomicrons and VLDL
Which lipoproteins are cholesterol rich?
HDL and HDL
Which lipoproteins are the densest?
HDL because of its high protein content, and low lipid content
Where are both forms of ApoB synthesised?
In ER in enterocytes
How are lipoproteins assembled?
Using different apolipoproteins, including ApoB48 and ApoB100
What is ApoB?
A lipid binding protein which comes in 2 different forms
What are the two different forms of ApoB?
ApoB48 and ApoB100
What does ApoB serve as the receiver of?
Lipids
How are chylomicrons assembled? (First Step)
Lipids combine with apoB via MTP in ER to form chylomicrons (ApoB particle)
How are chylomicrons assembled? (Second Step)
The chylomicron already produced + TAG via MTP creating a larger chylomicrons (larger ApoB)
What is MTP?
Microsomal triglyceride transfer protein
Where do chylomicrons go for maturation?
To golgi
Where are chylomicrons secreted from?
Intestinal cells entering the bloodstream via the lymphatic system
What appearance can chylomicrons give?
Give plasma a “milky” appearance after a fat-rich meal due to high TAG content
What do lipoproteins solubilise?
Lipids for transport in blood to tissues
What system do lipoproteins provide?
A delivery system for shifting lipids in and out of cells
What are the important functions of apoproteins?
- Assembly (apoB)
- Ligands for cell surface receptors (apos B and E)
- Enzyme cofactors
What hydrolyses lipids?
Lipoprotein and hepatic lipases
What factors affect lipid levels?
- Diet (SAFA increases, PUFA decreases TAG + LDL)
- Drugs
- Genetics
- Disease
What do statin drugs inhibit?
HMG-CoA
- Which lowers cholesterol levels and increases LDL receptor activity
What do ezetimibe drugs do?
Blocks cholesterol absorption from intestine, less cholesterol uptake in body, also upregulates LDL receptors
What drug do PUFA’s act similarly to?
Fibrates
What do both PUFA’s and fibrates do?
Both activate a transcription factor known as PPAR
What is the function of PPAR?
- When activated, switches on genes, one of them being lipoprotein lipase (LPL)
- LPL hydrolyzes the TAG which lowers the TAG content in your VLDL particles and therefore lower TAG levels in the blood
What is familial hypocholesterolemia (FH) caused by?
Defects in LDLR causing elevated LDL cholesterol
What do defects in apoB or MTP cause?
Low blood cholesterol levels
What do defects in LPL or ApoCII cause?
Elevated TAG levels
