Week 3 Lipoproteins Apolipoproteins in Lipid Metabolism Flashcards
What is the function of plasma Lipoproteins?
- their function is in the transport of lipids in the plasma
What types of molecules do plasma lipoproteins contain?
hydrophobic, hydrophilic, amphipathic molecules, also contain proteins (apolipoproteins)
What do lipoproteins do?
They keep lipids soluble and they transport lipids to and from various tissues
What are the 4 different types of plasma lipoproteins
- chylomicron (more TAG)
- VLDL (Less TAG)
- LDL (Less TAG)
- HDL (Lowest TAG)
What is the role of the chylomicron?
to transport TAG from the intestines to the peripheral tissues
What does lipoprotein destination depend on?
Their apolipoproteins
What is the role of apolipoproteins?
- recognition sites
- activators or coenzymes for enzymes
- structural
Assembly of amino acid B-48 requires?
MTP; ER/Golgi, chylomicron
When are new chylomicrons rapidly modified?
Once they reach the plasma
The addition of apoE and apoC-II leads to?
Recognition by hepatic receptors and activation of lipoprotein lipase (degrades the TAGs present in the chylomicron)
What stimulates lipoprotein synthesis and transfer to luminal surface of capillary?
Insulin
What do different TAGs have that help differentiate their different tissue-specific isoforms?
Km values for TAG
What happens when 90% of the TAGs are removed?
The chylomicron remnants return to the liver and are endocytosed and are degraded by the lysosome.
What is lipoprotein lipase activated by?
ApoCIII, stimulated by insulin
What does lipoprotein lipase do?
It causes the release of fatty acids and glycerol from TAGs in lipoproteins.
What the different LIPID transfer proteins?
HTGL
LCAT
CETP
What is the role of CETP?
Facilitates the exchange of cholesteryl esters for TAGs between HDL, VLDL and IDL, contributing to reverse cholesterol transport
What does cholesterol transported by lipoprotein back up?
It backs up the capacity of cells to synthesise cholesterol
What are the main stages of lipoprotein metabolism?
- assembly of lipoprotein particles (chylomicrons in the intestine)
- transfer of lipoprotein to peripheral cells (release of TAGs/FA from lipoproteins to cells)
- liver uptake
- generation of LDL particles
- reverse cholesterol transport
What are the 4 different types of apolipoproteins?
A, B, C, D, E (E1-4)
Individuals with E4 isoform are shown to be at an increased risk of a sporadic form of what?
Alzheimer Disease
What is the LDL receptor apoE/B regulated by?
Intracellular cholesterol concentration
What are scavenger lipoprotein receptors?
Nonspecific and nonregulated
What are the 3 functions of the liver?
Endocrine and exocrine
Food entering the duodenum stimulates the secretion of cholecystokinin and this is turn stimulates?
pancreatic enzyme production and secretion (bile release)
The acidity of the stomach contents entering the duodenum stimulates the release of secretin, what does this do?
It triggers the secretion of bicarbonate rich pancreatic fluid, which neutralises the acidity in the duodenum.
What is the most important biochemical marker present in pancreatitis?
Increased amylase activity in serum
What is chronic pancreatitis a consequence of?
Long term inflammation and leads to malnutrition and steatorrhea
Zollinger Ellison is a rare disorder involving what?
The chylomicron assembly being impaired.
In cystic fibrosis, which regulator protein is affected?
CF transmembrane conductance regulator protein
What is the treatment for cystic fibrosis?
Lipase enzyme replacement and vitamin supplementation
Where are VLDLs produced?
In the liver
What is the role of VLDL?
To provide cholesterol to peripheral tissues en route to the liver
What is atherosclerosis?
The hardening of the arteries.
What is the link between LDL and atherosclerosis?
LDL usually enters cells by receptor mediated endocytosis
Scavengers are not turned off with high cholesterol… uptake of oxidized LDL.. convert to foam cells
Foam cells contribute to plaque formation.
What is reverse cholesterol transport?
This is where direct HDL transport of cholesterol esters to the liver. Remnants is not taken up but sent back out to scavenge cholesterol and exchange apolipoprotein and TAG.
Familial Hypercholesterolemia involves? Which receptor?
The defect makes the body unable to remove LDL cholesterol from the blood. This results in high levels of LDL in the blood.
PCSK9 receptor
What does NAFLD involve?
deposition of excess TGs in the liver
What type of disease is Wolmans Disease and what is the deficiency?
Lysosomal acid lipase deficiency - certain fats may abnormally accumulate in the tissues and organs of the body.
Genetic - autosomal recessive - mutations