ChemPath: Lipoprotein metabolism, CVD and obesity Flashcards
What are the features of an atherosclerotic lesion?
- Fibrous cap
- Foam cells (macrophages full of cholesteryl ester)
- Necrotic core (full of cholesterol crystals)
What is the biggest plasma lipoprotein?
Chylomicrons
During what time will chylomicrons be most abundant?
After eating (they are present in very small amounts in the fasted state)
Describe the uptake of cholesterol by the intestinal epithelium.
- Cholesterol entering the intestines will come from the diet and bile
- Cholesterol will be solubilised in mixed micelles
- It is then transported cross the intestinal epithelium by NPC1L1 (this is the main determinant of cholesterol transport)
- balance between NPC1L1 and ABC G5,G8 determines amount of cholesterol absorbed
Name two transports that transport cholesterol back into the intestinal lumen.
ABC G5
ABC G8
Where are bile acids absorbed?
Terminal ileum
What happens when cholesterol arrives at the liver?
Downregulates the activity of HMG CoA reductase
NOTE: HMG CoA reductase is responsible for the production of cholesterol from acetate and mevalonic acid
If more cholesterol absorbed in SI, less will be made by liver
What are the two fates of cholesterol that is either produced by or transported to the liver?
- Hydroxylation by 7a-hydroxylase to produce bile acids
- Esterification by ACAT to produce cholesterol ester which is incorporated into VLDLs along with triglycerids and ApoB
VLDL is precursor for LDL
Which transfer protein is important in the packaging of VLDLs?
MTP
Which transfer protein is important in the packaging of HDLs?
ABCA1
What are the effects of CETP on the movement of substances between lipoproteins?
- Moves cholesterol from HDL → VLDL
- Moves triglycerides from VLDL → HDL
Which receptor is responsible for the uptake of some HDLs by the liver?
SR-B1
Describe the transport and metabolism of triglycerides.
- Triglycerides from fatty foods are hydrolysed to fatty acids, absorbed, and resynthesized into triglycerides which are transported by chylomicrons into the plasma
- Chylomicrons are hydrolysed by lipoprotein lipase into free fatty acids
- Some free fatty acids are taken up by the liver, and some by adipose tissue
- The liver resynthesizes fatty acids into triglycerides and packages them into VLDLs
- VLDLs are acted upon by lipoprotein lipase to liberate free fatty acids
List the three causes of familial hypercholesterolaemia (type II).
- Caused by autosomal dominant gene mutations in:
- LDL receptor
- ApoB
- PCSK9
List some mutations that are implicated in polygenic hypercholesterolaemia.
- NPC1L1
- HMGCR
- CYP7A1