Lipids and Lipoproteins Flashcards
What are the sources of cholesterol?
Diet and synthesised by liver from Acety CoA
How is cholesterol excreted?
Bile acids
How is cholesterol regulated in the body?
Negative feedback - inhibits further synthesis of itself by inhibiting HMG-CoA reductase
Insulin/glucagon control - insulin → increases synthesis; glucagon → decreases synthesis
Long term control - inhibition of HMG-CoA reductase → decrease cholesterol
also: reduced cellular uptake by inhibition of cholesterol receptor expression
What is the basic lipoprotein structure?
Non-polar lipid core - mostly TAGs and cholesterol esters
Polar (hydrophilic) outer coat
What is a chylomicron?
Takes TAGs from small intestine → tissues
What do VLDLs do?
Take TAGs from liver → tissues
What is IDL?
Remnant of VLDL and can form LDLs
What are LDLs?
Take cholesterol esters from IDL → tissues
What is HDL?
Free cholesterol scavenger in periphery → liver
How are long chain FAs transported from the intestine?
Converted to TAGs, packaged into chylomicrons → secreted into lacteals
(Exogenous pathway)
how are short and medium chain FAs transported from the intestine?
Secreted into bloodstream as FFAs
Increase in FFAs in blood → insulin secretion → encourage uptake by liver/muscle/tissue
Decrease FFAs in blood between meals → adipocyte release of FFAs
Diagram for major groups of lipoproteins and their actions
What does the exogenous lipid transport pathway include?
Takes lipids from small intestine → tissues via chylomicrons
- Chylomicrons secreted into lymph system by intestinal mucosal cells
- Chylomicrons acquire apolipoproteins from HDL circulating in blood (apoC and apoE)
- CMs and TAGs broken down → FFAs by lipoprotein lipase (apoC) for the tissues to absorb
- Remnants taken up by liver (apoE)
What is involved in the endogenous pathway?
Takes TAGs and Cholesterol to tissues via VLDL → IDL → LDL
- VLDL synthesised in the liver (TAGs + apolipoproteins/cholesterol)
- TAGs removed by lipoprotein lipase in capillaries → IDL
- Majority IDL donates apolipoproteins to HDL → becomes LDL
- LDL taken up by peripheral tissues (provide cholesterol)
What does reverse cholesterol transport invovle?
Transports free/used cholesterol back to the liver
HDL scavengers: free cholesterol in peripheries → liver
Provides apolipoproteins to CMs, VLDL, IDL
What is the clinical definition of familial hypercholesterolaemia?
Increased total cholesterol or LDL
+ Tendon Xanthoma in patient or close relative
What is xanthelasma?
Yellow flat plaques on upper/lower eyelids - lipid-containing macrophages condensing around the socket
Usually due to high cholesterol/atheromatous disease
What is corneal arcus?
Grey opaque line surrounding margin of cornea
Common in Type II Diabetes
What is the pathophysiology of Familial Hypercholesterolaemia?
Genetic disorder - autosomal dominant, though varying effect with homo/heterozygous
Causes LDL Receptor dysfunction - prevents proper uptake of LDL by cells
What investigations can be used for diagnosis of Familial Hypercholesterolaemia?
Bloods
Total cholesterol >7.5mmol/l
LDL >4.9mmol/l
Plus tendon xanthoma → diagnosis
What is the treatment for Familial Hypercholesterolaemia?
Diet/lifestyle
Treatment of associated conditions
Statins - decrease cholesterol synthesis and increase LDL uptake; increase atherosclerotic plaque stability
Fibrates - decrease hepatic secretion + increase peripheral uptake → decrease serum triglyceride
Increase gallstone risk by increasing choleseterol content of bile
