Lipids and Lipoproteins

Question 1

What are the sources of cholesterol?

Answer 1

Diet and synthesised by liver from Acety CoA

Question 2

How is cholesterol excreted?

Answer 2

Bile acids

Question 3

How is cholesterol regulated in the body?

Answer 3

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

Question 4

What is the basic lipoprotein structure?

Answer 4

Non-polar lipid core - mostly TAGs and cholesterol esters

Polar (hydrophilic) outer coat

Question 5

What is a chylomicron?

Answer 5

Takes TAGs from small intestine → tissues

Question 6

What do VLDLs do?

Answer 6

Take TAGs from liver → tissues

Question 7

What is IDL?

Answer 7

Remnant of VLDL and can form LDLs

Question 8

What are LDLs?

Answer 8

Take cholesterol esters from IDL → tissues

Question 9

What is HDL?

Answer 9

Free cholesterol scavenger in periphery → liver

Question 10

How are long chain FAs transported from the intestine?

Answer 10

Converted to TAGs, packaged into chylomicrons → secreted into lacteals

(Exogenous pathway)

Question 11

how are short and medium chain FAs transported from the intestine?

Answer 11

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

Question 12

Diagram for major groups of lipoproteins and their actions

Answer 12

Question 13

What does the exogenous lipid transport pathway include?

Answer 13

Takes lipids from small intestine → tissues via chylomicrons

1. Chylomicrons secreted into lymph system by intestinal mucosal cells
2. Chylomicrons acquire apolipoproteins from HDL circulating in blood (apoC and apoE)
3. CMs and TAGs broken down → FFAs by lipoprotein lipase (apoC) for the tissues to absorb
4. Remnants taken up by liver (apoE)

Question 14

What is involved in the endogenous pathway?

Answer 14

Takes TAGs and Cholesterol to tissues via VLDL → IDL → LDL

1. VLDL synthesised in the liver (TAGs + apolipoproteins/cholesterol)
2. TAGs removed by lipoprotein lipase in capillaries → IDL
3. Majority IDL donates apolipoproteins to HDL → becomes LDL
4. LDL taken up by peripheral tissues (provide cholesterol)

Question 15

What does reverse cholesterol transport invovle?

Answer 15

Transports free/used cholesterol back to the liver

HDL scavengers: free cholesterol in peripheries → liver

Provides apolipoproteins to CMs, VLDL, IDL

Question 16

What is the clinical definition of familial hypercholesterolaemia?

Answer 16

Increased total cholesterol or LDL

+ Tendon Xanthoma in patient or close relative

Question 17

What is xanthelasma?

Answer 17

Yellow flat plaques on upper/lower eyelids - lipid-containing macrophages condensing around the socket

Usually due to high cholesterol/atheromatous disease

Question 18

What is corneal arcus?

Answer 18

Grey opaque line surrounding margin of cornea

Common in Type II Diabetes

Question 19

What is the pathophysiology of Familial Hypercholesterolaemia?

Answer 19

Genetic disorder - autosomal dominant, though varying effect with homo/heterozygous

Causes LDL Receptor dysfunction - prevents proper uptake of LDL by cells

Question 20

What investigations can be used for diagnosis of Familial Hypercholesterolaemia?

Answer 20

Bloods

Total cholesterol >7.5mmol/l

LDL >4.9mmol/l

Plus tendon xanthoma → diagnosis

Question 21

What is the treatment for Familial Hypercholesterolaemia?

Answer 21

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