4 Lipid Transport Flashcards
What are Hyperlipoproteinaemias?
Raised plasma levels of 1+ lipoprotein classes
What (in general terms) causes hyperproteinaemias?
Defects in: Enzymes, receptors, apoproteins
Under removal/over production
Specifically, what causes each type of hyperlipoproteinaemia? (6)
What is hyper cholesterolaemia?
High cholesterol levels in blood–>cholesterol depostions in areas of body
What are some of the symptoms of hypercholesterolaemia? (3)
- Xanthelasm: yellow patches on eyelids
- Tendon xanthoma: nodule on tendon
- Corneal Arcus: white circle around eye
What is the first line of treatment for hyperlipoproteinaemias?
LIFESTYLE MODIFICATION
-
Diet
- Reduce cholesterol, saturated lipids
- Increase fibre–> sequester bile salts
- Increase exercise
- Stop smoking
What drugs are used to treat hyperlipoproteinaemias if lifestyle modifications dont work?
-
Statins (Atorvastatin)
- reduce cholesterol synthesis
- inhibit HMG-CoA reductase
-
Bile Salt sequestrants (Colestipol)
- __bind bile salts in GI tract
- liver forced to produce more bile acids- uses up cholesterol
How does benecol reduce cholesterol levels?
Contains a molecule which bind preferentially to cholesterol
What are the ideal cholesterol plasma levels?
Total: 5mmol/L or less
If total cholestrol: HDL-cholesterol ratio is >6 then= high risk
Which vitamins are classed as lipids?
Vitamins A, D, E, K
In what form are the majority (98%) of lipids transported in the blood?
Lipoprotein particles
Phospholipid, cholesterol, cholesterol esters, proteins and TAG (triacylglycerol)
Apart from in the form of lipoprotein particles, how else can lipids be transported in the body (2%)?
Bound to albumin
Describe the structure of a phospholipid. (which part is hydrophobic and which part is hydrophilic)
How is cholesterol obtains for use in the body? (2)
- Synthesised by Liver (most)
- Diet
Give 3 functions of cholesterol in the body.
- Modulate fluidity
- Precursor for steroid hormones
- Cortisol, aldosterone, testosterone, oestrogen
- Prescursor for bile acid
In what form is cholesterol transported in the body?
Cholesterol ester
This image shows the structure of a lipoprotein. Label each of the arrows:
One of the 5 classes of Lipoproteins is HDL (high density lipoproteins). What are the other 4?
- Chylomicrons
- VLDL
- IDL
- LDL
- (HDL)
Out of the 5 classes of lipoproteins (Chylomicrons, VLDL, IDL, LDL, HDL) which ones are:
- The main carriers of fat
- The main carriers of cholesterol esters
What method do we use to measure the density of lipoproteins in blood plasma?
Flotation ultracentrifugation
Apoliproteins complement lipoproteins and can be integral or peripheral. What are the 6 major classes of Apoliproteins?
(Think simple)
- ApoA
- ApoB
- ApoC
- ApoD
- ApoE
- ApoH
ApoB and ApoA are either (VLDL, IDL, LDL, HDL). Identify which type of Lipoprotein these apoliproteins can be.
apoB = VLDL, IDL, LDL
apoA = HDL
Where in the body are chylomicrons loaded?
Small intestine
Identify the apoliprotein which is added to th echylomicrons before they enter the lymphatic system.
apoB-48
Fill in the missing gaps:
A chylomicron is formed in the ______ in the body. It then enters the ______ system. Once the chylomicron enters the left subclavian vein from the _____ duct, it acquires apo_ and apo_. apo_ binds to ________ _______ (which is found on adipocytes and muscle) , which allows fatty acids to be released from chylomicrons and enter cells.
Fill in the missing gaps:
A chylomicron is formed in the small intestine in the body. It then enters the lymphatic system. Once the chylomicron enters the left subclavian vein from the thoracic duct, it acquires apoC and apoE. apoC binds to lipoprotein lipase (which is found on adipocytes and muscle) , which then allows fatty acids to be released from chylomicrons and enter cells.
Which organ in the body are chylomicron remnants returned to?
Liver
Fill in the gaps:
Once the chylomicron remnants return to the liver, they have now become ___. There are ___ receptors on hepatocytes which allow for receptor mediated ______. Lysosomes release their contents.
Once the chylomicron remnants return to the liver, they have now become LDLs. There are LDL receptors on hepatocytes which allow for receptor mediated endocytosis. Lysosomes release their contents.
What is the function of VLDL made in the liver?
Transporting TAG to other tissues
What is the name of the enzyme that VLDLs bind to on endothelial cells in muscle and adipose to become depleted of TAG?
Lipoprotein lipase
What is the main function of LDLs?
Provide cholesterol from the liver
(IDL= short lived)
Why are LDLs not efficiently cleared by the liver?
Hint: Lacking …….
apoC and apoE
Why are LDLs more susceptible to oxidative damage than VLDLs and IDLs?
LDLs have much longer half life than VLDLs and IDLs
What happens to oxidised LDLs?
- Taken up by macrophages
- Transformed into foam cells
- Contribute formation of atherosclerotic plaques
apoB-100 can be found on LDLs. What is the function of this apoliprotein?
Functions as ligand
Binds to LDL receptor on cell requiring cholesterol
How are HDLs synthesised? (3 ways)
- By liver and small intestine
- Bud off from chylomicrons & VLDLs when digested by LPL
- Free apoA-I can acquire cholesterol and phospholipid from other lipoproteins- form HDLs
HDLs do not require enzyme activity to mature. How do they mature?
- Accumulate phospholipids and cholesterol…
- …from cells lining blood vessels…
- …hollow core- fills
What is the main function of HDLs?
- Removes cholesterol from cholesterol laden cells
- –> returns it to liver
- Reduces foam cell and plaque formation in blood vessels
Name the molecule which facilitates the transfer of cholesterol to a HDL.
ABCA1
(then cholesterol converted to cholesterol ester by LCAT)
Which organ takes up the mature HDL?
Liver
Describe the 2 ways in which HDLs can be used once taken up by the liver.
- Exchange cholesterol ester via CETP (cholesterol exchange transfer protein) for TAG with VLDL
- Cells requiring aditional cholesterol- use SR-B1 (scavenger receptor) to obtain cholesterol from HDL
