Lipid Transport Flashcards
What are 2 ways lipids can be transported in blood?
Which is the main one
- Bound to albumin
- Carried as lipoprotein particles
As lipoproteins
Compare Phosphatidylcholine and Phosphatidylinositol
phosphatidylcholine: Choline head group attached to phosphate
Phosphatidylinositol: Inositol head group attached to phosphate
How is cholesterol obtained?
How is it transported around the body
- Some from diet, mostly made in liver
- transported as a Cholesterol ester (Cholesterol + Fatty acid tail)
What is cholesterol a precursor of
Give 4 examples
Steroid hormones
Cortisol
Aldosterone
Testosterone
Oestrogen
Describe the structure of a lipoprotein
- Phospholipid monolayer with some cholesterol
- Peripheral, Integral Apolipoproteins
- Cargo consisting of fat soluble vitamins, cholesterol ester, TAG
Name the 5 Lipoprotein types
- Chylomicrons
- VLDL (Very Low Density)
- IDL
- LDL (Low Density)
- HDL
What are the main carriers of fat
What are the main carriers of cholesterol esters
Fat: Chylomicron+ VLDL
Cholesterol Esters: IDL, LDL, HDL
Which Lipoproteins can change into each other, and how is the diameter related to the density
VLDL—>IDL—>LDL
Diameter inversely proportional to Density
What is an Apolipoprotein
What are 2 important ones and which lipoproteins are they on?
A protein on the outer surface of a lipoprotein
apoB- VLDL, IDL, LDL
apoA1- HDL
Explain the 2 functions of apilopoproteins
Structural: Packaging water insoluble lipid
Functional: Co-factor for enzymes
Ligands for cell surface receptors
Explain Chylomicron metabolism in 5 steps
- Chylomicrons loaded in Small Intestine, apoB-48 added before entering Lymphatic System
- Empty into Left Subclavian Vein, acquire apoC and apoE
- apoC binds Lipoprotein Lipase (LPL) on Adipocytes and Muscle. Fatty acid released, depleting chylomicrons of fat content
- When triglyceride=20%, apoC dissociates and Chylomicron becomes Chylomicron Remnant
- Chylomicron remnant returns to liver. LDL receptor on hepatocyte binds apoE, and remnant taken up by Receptor Mediated Endocytosis. Lysosomes release remaining contents
Explain VLDL Metabolism in 4 steps
What happens in the tissues (Included in the steps)
- During formation, apoB100, apoC, apoE added
- VLDL binds to Liprprotein Lipase (LPL) in Muscle and Adipose Endothelial cells, starts losing TAG
- In muscle, fatty acids are used for energy production
- In adipose, fatty acids are used to re-make TAG and stored as fat
Explain IDL and LDL are made and metabolised
- As TAG content of VLDL particles drop, they dissociate from LPL or go to liver
- If TAG content reaches 30%, particle becomes IDL
- IDL can either be taken up liver or rebind to LPL
- If TAG content reaches 10%, IDL loses apoC, apoE and becomes LDL particle
How is LDL taken up by cells
What is the effect of LDL not having apoC or apoE
- Cells with an LDL Receptor take up LDL by Receptor Mediated Endocytosis
- No apoC or apoE, so not efficiently cleared by liver
State the functions of;
- apoB-100
- apoC
- apoE
- Binds to LDL Receptors in cells needing cholesterol
- Binds to LPL on Adipocytes and Muscle
- Binds to LDL receptors in liver
Which cholesterol-containing lipoprotein is ‘good’
Which is ‘bad’
Bad- LDL
Good-HDL
Give 3 ways in which HDL can be formed
- Nascent HDL made by Liver
- HDL particles can also “bud off” from chylomicrons and VLDL as they get digested by LPL
- Free apoA-1 can take cholesterol from other lipoproteins and cell membranes to form nascent-like HDL
How do nascent HDL particles mature
Is an an enzyme needed to transfer lipids to HDL
Accumulate cholesterol from cells lining blood vessels, take on more globular shape
No
Explain Reverse Cholesterol Transport
ABCA1 protein in cell facilitates cholesterol transfer to HDL
Cholesterol then converted to cholesterol ester by LCAT
What 3 things can happen to mature HDL
- Taken up by liver
- SR-B1 used by cells to acquire cholesterol from HDL
- Cholesterol ester can be exchanged with TAG from VLDL by CETP (Cholesterol Exchange Transfer Protein)
Outline the functions of the 5 classes of Lipoproteins
Chylomicrons: Transport dietary TAG from intestine to tissues
VLDL: Transport TAG made in liver, to adipose/ muscle tissue
IDL: Precursor of LDL, Transport cholesterol made in liver to tissues
LDL: Transport cholesterol made in liver to tissues
HDL: Transport excess cholesterol from tissues to liver
What happens to the cholesterol taken to the liver
Disposal as bile salts OR transferred to cells requiring additional cholesterol
What are 2 causes of Hyperlipoproteinaemias
- Over-production
2. Under-removal
Describe 3 symptoms of Hypercholesterolaemia
Xanthelasma: Yellow patches on eyelids
Tendon Xanthoma: Nodules on tendon
Corneal Argus: White circle around eye (Common in older people, could be a symptom if in younger people)
How does High Serum LDL lead to Atherosclerotic plaque
Oxidised LDL-> Engulfed by macrophages
Foam cells gather to to form fatty streak in intima of blood vessel
Streak evolves into atheroscelrotic plague
How does an Atherosclerotic plague cause;
- Angina
- Stroke and Myocardial infarction
- Plaque encroaches on artery lumen
2. Plaque ruptures, triggering acute thrombosis
What are the 2 approaches in treating Hyperlipoproteinaemias
1st approach:
- Reduce cholesterol intake, increase fibre intake (encourages bile salt production using cholesterol)
- Increase exercise, stop smoking
If no response,
- STATINS (Inhibit HMG-CoA reductase to reduce cholesterol synthesis)
- Bile salt sequesterants (Bind biles salts in GI Tract)
What is Type 1 Hyperlipoproteinaemia
Chylomicrons in fasting plasma, Defective LPL
Not associated with coronary artery disease
What is Type 2a Hyperlipoproteinaemia
Defective LDL receptor, associated with coronary artery disease
What is Type 3 Hyperlipoproteinaemia
Defective apoE.
Raised IDL and chylomicron remnants.
Associated with coronary artery disease
