Lipid Transport

Question 1

What are the 5 types of lipids?

Answer 1

• Triacylglycrerol
• Fatty acids
• Cholesterol
• Phospholipids
• Vitamins (A, D, E and K)

Question 2

Describe cholesterols

Answer 2

• synthesised in the liver
• essential for regulating membrane fluidity
• precursor of steroid hormones and bile acids
• transported as cholesterol ester

Question 3

What are lipoproteins?

Answer 3

Biochemical assemblies of lipids and proteins to transport the lipid portion in the blood

Question 4

What are the five classes of lipoproteins?

Answer 4

• Chylomicrons
• VLDL (very low density lipoproteins)
• IDL (intermediate density lipoproteins)
• LDL (low density lipoproteins)
• HDL (high density lipoproteins)

each contains variable content of apolipoproteins, TAG, cholesterol and cholesterol esters

Question 5

What are apolipoproteins?

Answer 5

Proteins that bind to lipids to package them into soluble particles (lipoproteins)
-apoB (VLDL, IDL, LDL) and apoA1 (HDL) are the most important

Question 6

Describe how chylomicrons come about

Answer 6

1) Dietary lipids absorbed in the intestine (hydrolysed first to fatty acids and glycerol)
2) Re-esterification to triacylglycerols and packaged into chylomicrons
3) apoB-48 added before entering lymphatic system
4) Enters the bloodstream which empties into left subclavian vein and gains 2 new apoproteins (C+E)
5) In the capillary walls of the target tissue (muscle and adipose), lipoprotein lipase hydrolyses them to release fatty acids (apoC binding)

Question 7

What happens to the remainder of chylomicros (chylomicron remnants)?

Answer 7

1) When chylomicrons release their fatty acids to target tissues (by lipoprotein lipase), apoC dissociates when TAG reduced to ~20%
2) Chylomicron remnant goes to the liver, apoE and chymicron taken up via receptor mediated endocytosis

Question 8

Where is VLDL made?

Answer 8

Liver

Question 9

What is the purpose of VLDL?

Answer 9

transporting triacylglycerol to other tissues from the liver

Question 10

Which apolipoprotein is added during the formation of VLDL

Answer 10

apoB100 (apoC+E added later from HDL)

Question 11

How does VLDL release its contents to target tissues?

Answer 11

Binds to lipoprotein lipase on endothelial cells in muscle and adipose (same as chylomicrons)

Question 12

How are IDLs formed?

Answer 12

when VLDL content further depletes to ~30% than returning to the liver

Question 13

How are LDLs formed?

Answer 13

Further depletion of IDLs to ~10% and apoC and apoE are lost

Question 14

What is the purpose of LDL?

Answer 14

provide cholesterol from the liver to preipheral tissues (that have LDL receptors in them to be taken up by endocytosis)

Question 15

What is the clinical relevance of LDLs?

Answer 15

• LDLs have a longer half life (than VLDL or IDL) this makes them more suceptuble to oxidative damage
• oxidised LDLs are phagocytosed by macrophages which ultimately leads to atherosclerotic plaques

Question 16

Briefly describe the process of Atherosclerosis

Answer 16

1) Oxidised LDL phagocytosed = foam cells
2) Foam cells acumulate in the intima = fatty streaks
3) Fatty streaks evolve to atherosclerotic plaques
4) Growth of plaques lead to angina
5) Further growth leads to ruptured vessels activating acute thrombosis = stroke or myocardial infarction

Question 17

Where are nascent (empty) HDLs synthesised?

Answer 17

Liver

Question 18

What is the function of HDLs?

Answer 18

Transport excess cholesterols from cells back to the liver or steroidogenic cells to give cholesterol to form steroid hormones

• can take TAGs from LDLs
• prevent foam cells forming

Question 19

What is hyperlipoproteinaemia?

Answer 19

Raised plasma level of one or more lipoprotein classes

-overproduction or under removal

Question 20

What is hypercholesterolaemia?

Answer 20

High level of cholesterol in the blood

Question 21

What is Xanthelasma?

Answer 21

Yellow patches on the eyelids (cholesterol deposits)

Question 22

What is tendon Xanthoma?

Answer 22

Nodules on tendons (cholesterol deposits)

Question 23

What is corneal arcus?

Answer 23

White circle around the iris of the eye (cholesterol deposits)

Question 24

How is hyperlipoproteinaemia treated?

Answer 24

• Diet
• Lifestyle
• Drugs (statins or bile salt sequestrants)

Question 25

Describe the mechanism of statins

Answer 25

Inhibits HMG-CoA reductase

-an enzyme in cholesterol synthesis

Question 26

Describe the mechanism of bile salt sequestrants

Answer 26

They bind bile salts in the GI tract which forces liver to produce more bile acids thus using more cholesterol