Chloesterol and Lipid Metabolism Flashcards
are lipids soluble in water?
insoluble/sparingly soluble
what are some of the functions of lipids?
essential for cell membrane makeup
energy
polar/non-polar lipds are transported in the blood within liproproteins?
non-polar
cholesterol and triglycerides are examples of what type of lipids?
non-polar
Name the 2 common lipoproteins commonly transported within the blood?
HDL, LDL
What are the levels like in LDL and HDL in cardio disease?
elevated LDL (or particles rich in triacylglycerols; TAGs) decreased HDL
Name the constituents of the lipoproteins
hydrophobic core
hydrophilic coat
apoproteins
What does the hydrophobic core of lipoproteins contain?
esterified cholesterol and triacylglycerols (TAGs)
What does the hydrophilic coat of lipoproteins contain?
monolayer of amphipathic cholesterol, phospholipids and some apoproteins
What allows lipoproteins to bind to cells?
apoproteins being recognised by receptors in the liver and other tissues
What are the apoproteins in HDL?
apoA1 + apoA2
What are the apoprotein(s) in LDL?
apoB100
What is the apoprotein in VLDL?
apoB100
What are the chylomicrons’ apoproteins?
apoB48
What do apoB containing lipoproteins do?
deliver triglycerides to muscle for ATP biogenesis and to adipocytes for storage
Where are Chylomicrons formed?
intestinal cells
What apoB lipoprotein transports dietary triglycerides and via which pathway?
chylomicrons and exogenous pathway
Where are VLDL particles formed?
liver cells
What apoB lipoprotein transports triglycerides synthesised in that organ and via which pathway?
VLDL
endogenous pathway
Describe the vague 3 steps in the life cycle of lipoproteins
Assembly > Intravascular metabolism > Receptor Mediated Clearance
In the assembly of Chylomicrons what does the digestion of dietary fat lead to?
triglycerides +cholesteryl ester into enterocyte
Where are enterocytes converted into chylomicrons?
Endoplasmic Reticulum
How are VLDL particles assembled in the liver?
from free fatty acids derived from adipose tissue (particularly during fasting) and de novo synthesis
How do chylomicrons and VLDL become activated?
by the transfer of apoCII from HDL particles
What happens once Chylomicrons and VLDL are activated?
Lipoprotein lipase then binds to them at the vascular wall via the apoCII and this then allows the breakdown into fatty acids and monoglycerides.
Describe the Intravascular Metabolism of apoB-containing Lipoproteins?
LPl binds to them via apoCII hydrolyses core triglycerides to free fatty acids leaving Chylomicron and VLDL remnants
Describe how apoB-containing lipoproteins are cleared from the body?
dissociated from LPL, apoE replaces apoCII and is a receptor for mediateing clearance to the liver
hepatic lipase metabolises them
think apoEXIT
What is ‘BAD’ cholesterol?
LDL
Describe how LDL cholesterol forms atheromatous plaque with a fibrous cap?
Dysfunction and injury of lining (endothelium) of blood vessels.
- uptake of LDL from into the intima, oxidised to atherogenic oxidised LDL (OXLDL)
- Monocytes migrate across endothelium into the intima where they become macrophages
- Uptake of OXLDL by macrophages converts them to cholesterol laden foam cells that form a fatty streak.
- Release of inflammatory substances from various cell types causes division and proliferation of smooth muscle cells into the intima causing collagen deposition.
- Atheromatous plaque forms with a fibrous cap.
Why is HDL deemed good
removes excess cholesterol from cells by transporting it in plasma to the liver and it is the only thing that can eliminate cholesterol by secreting it into bile
What is the only organ that can process cholesterol?
the liver
What can reduce LDL by up to 60%? How?
statins
competive inhibitors of HMG CoA reductase rate limiting step in cholestorl synthesis in hepatocytes in the LIVER.
The decrease in hepatocyte cholesterol synthesis causes a compensatory increase in LDL receptor expression and enhanced clearance of LDL
How and when are statins administered and what do they do apart from decrease LDL?
orally at night
decrease inflammation
reverses endothelial dysfunction
decreases thromvosis
What is a bad side effect of statins?
muscle necrosis
What do Fibrates do?
decreases triglycerides in 1st line
agonist of PPAR alpha which enhances the transcription of Lipoprotein lipase
Name 2 fibrates
bezafibrate
gemfibrozil
Name 3 bile acid binding resins
colestyramine
colestipol
colsevelam
How do bile acid binding resins work?
bind to bile salts preventing them from being reabsorbed this means that more cholesterol is picked up from the blood resulting in decreased levels of hyperlipidaemia(containing cholesterol) so preventing more cholesterol absorption.
cause decreased absorption of triglycerides and increased LDL receptor expression.
What does the drug Ezetimibe do?
inhibits NPC1L1 transport protein in enterocytes of duodenum, reducing absorption of cholesterol, decreasing LDL.
