Lipoprotein handeling Flashcards
What are the different forms of fatty acids?
Triglycerides (90%), cholesterol, cholesterol esters, phospholipids, free fatty acids
Which forms of fatty acid is hydrophobic? What is the consequence of this?
Triglycerides and cholesterol
They have to be transported as lipoproteins
What is located on the outer coat of lipoproteins?
Phospholipids
Free cholesterol
Proteins (apoproteins)
What is located on the inner coat of lipoproteins?
cholesterol
cholesterol esters,
Triglycerides
Vitamins (e.g. A and E)
What are the three main transportation paths for lipoproteins?
Gut (food)—–> rest of the body
Liver——–> Peripheral tissues
Peripheral tissues——-> liver
What do apoproteins determine in the lipoprotein?
- Fate of the lipoprotein
- Interactiosn of the lipoprotein
- Inhibition and activation of certain enzymes
How are reactive oxygen species formed in the TCA cycle?
When electrons are not transported efficiently
What are reactive oxygen species?
High energy molecules
Cause damage of proteins, lipids, DNA
What is hypoxia? What is its effect on ROS’s
Low oxygen concentration
Causes the production of more ROS’s as there is a low amount of oxygen to mop up electrons
How do cells adapt to hypoxic situations?
Limits the amount of ATP needed
Improves the efficiency of anaerobic ATP production
Limits oxidative stress to prevent tissue damage
Which gene/protein enables the tissue to adapt to hypoxic situations? How does it work?
Hypoxia-induced factor-1 (HIF1)
During normal conditions HIF1 is broken down
During hypoxia, HIF1 is activated and moves to the nucleus where it acts as a transcription factor switching on genes which enable the cell to survive low oxygen conditions
What does activation of HIF1 cause?
Reduces mitochondria by promoting its degradation
Inhibits synthesis of new mitochondria by blacking PGC1 activity.
So less TCA less ROS produced
How is HIF1 an oncogen?
Allows cancer less to survive in low oxygen environments. Potential target for cancer drug therapy
What is leigh syndrom? What does it cause?
Genetic hereditary mutation in the genes for ECT causing loss of oxidative metabolism in ATP production.
Causes death to cells dependant on ATP e.g brain, nerves muscles
Death after 2/3 years (respiratory)
What is the main component and apoprotein in
Chylomicrons, VLDL,IDL,LDL and HDL?
Chylomicrons- Comp-TAG apo-B48 VLDL- comp-TAG apo-B100(A,C,E) IDL- comp- TAG, cholestral apo-B100(E) LDL-comp- cholestral apo- B100 HDL- comp-protein apo-AI,AII
What is the function of apoB-100?
Controls the metabolism of LDL’S
What is the function of B48?
Controls the uptake of chylomicrons
What is the function of ApoE and Apo C
Apo E- controls the binding of lipoproteins to receptors on the cell membrane
Apo C- Enzyme inhibitor
What is the function of Chylomicrons? How is it formed?
Formed in the gut- during digestion
Carries fat/ cholesterol from GI to peripheral tissues
What is the function of VLDL? How is it formed?
Formed in the liver
carries triglycerides to peripheral tissues
How is it IDL formed?
Formed from partly absorbed VLDL in periphery
How is it LDL formed?
remnants of VLDL and IDL which enter circulation and transport cholesterol around to peripheral tissues
What are HDL’s?
Scavengers of cholesterol from peripheral tissue which transport cholesterol esters to the liver to make VLDL and LDL
Describe the metabolism of chylomicrons
Absorbed from fats and cholesterol, absorbed from the GI and pass into the lymphatics before entering the blood
In lymphatics they interact with HDL which donates Apo E and C2
Functions of Apo E and C2 in relation to chylomicrons
ApoE- Allows chylomicron remnants to be taken up by the liver
ApoC2- Allows chylomicrons to give TAG to peripheral tissues
Describe the formation of VLDL
Produced by the liver
Requires the addition of ApoC2 and ApoE from HDL to mature
Remanats are either reabsorbed by the liver or become LDL
What is the function of lipoprotein lipase?
Breaks down TAG in chylomicrons and VLDL’s into free fatty acids which can be taken up by periphery cells
Which apoprotein acn activate lipoprotein lipase?
ApoC2
Describe lipoprotein lipase activity during starvation
Activity is highest in muscles where FA are used to make ATP from the TCA cycle
During starvation what happens to fat?
Its is transported from liver to muscle to be used to make energy
Describe lipoprotein lipase activity after a meal
Activity is highest in adipose to form fat via esterficaction
What do chylomicrons and VLDL’s mostly transport?
TAG
Which lipoprotein mostly transports cholestral?
LDL’s
How are IDL’s converted into LDL’s?
IDL’s are absorbed by the liver
The enzyme hepatic TAG ligase converts IDL’s to LDL’s (high in choesteral, only has Apo100)
How is LDL taken up by target cells?
ApoB100 binds to LDL receptors on target cells and allows receptor mediated endocytosis (taken up by target cells)
Why can LDL’s stay longer in circulation?
They lack ApoE
What is familial hypercholesterolemia?
Autosomal dominant genetic condition
Causes mutations in 3 genes:
1. LDLR- receptor for receptor mediated endocytosis of LDL’s
2. PSCK9- Kinase enzyme which controls the amount of LDL receptor produced
3. APOB- Gene for ApoB 100 which binds to LDL receptor on target cells
Causes high levels of LDL to accumulate in the blood
List the important functions of HDL
Can exchange molecules (apoproteins,cholesterol,TAG) with other lipoproteins
Made in the liver and small intestine
Transports used cholesterol back to the liver for disposal
When produced in the liver it makes mainly ApoA1
