L4 - Lipid Transport

Question 1

2% of lipids are transported in the blood attached to albumin, the rest are carried as what?

Answer 1

lipoproteins

Question 2

What is the recommended range for plasma cholesterol?

Answer 2

<5mMol/L

Question 3

Some cholesterol is obtained from the diet but most is synthesised in the liver. List three major functions of cholesterol

Answer 3

• Modulates membrane fluidity
• Precursor of steroid hormones
• Precursor of bile acids

Question 4

Give some lipids that are transported within the micelles of lipoproteins

Answer 4

triglycerides/cholesterol esters (transportable form)/Fat soluble vitamins (A,D,E and K)

Question 5

lipoproteins consist of three major things, a phospholipid monolayer, it’s cargo (lipids) and apoliporproteins which bind the lipids. These apolipoproteins can be peripheral or ______

Answer 5

integral

Question 6

What do chylomicrons transport specifically around the bloodstream?

Answer 6

dietary fats

Question 7

VLDL’S transport fats made in the liver, as they travel around the bloodstream and deplete their cargo they become IDL’s and then _____

Answer 7

LDL’s

Question 8

what do HDL’s do?

Answer 8

transport cells excess cholesterol to the liver

Question 9

How long are chylomicrons present for after eating a meal?

Answer 9

4 hours

Question 10

Order these in DENSITY, highest to lowest 
chylomicrons
idl's 
ldl's
hdl's
vldl's

Answer 10

HDL's
LDL's
IDL's
VLDL's
Chylomicrons

Question 11

Which lipoproteins express apoB and which express apoA1? (important)

Answer 11

apoB - VLDL, IDL, LDL apoA1 - HDL

Question 12

Give two functions of the apolipoproteins

Answer 12

• package lipids
• act as co-factors for enzymes
• act as ligands for cell-surface receptors

Question 13

Chylomicrons containing dietary fats are loaded with cargo and the apoB-48 apolipoprotein in the small intestine before entering the lymphatics. Briefly describe their path from here to their breakdown in the liver

Answer 13

Enter the subclavian vein via the thoracic duct into the circulation and acquire ApoC and ApoE.

ApoC binds LDL on tissues and muscle, this releases the fatty acids and when triglyceride levels reach 20% apoC dissociates and the chylomicron becomes a remnant

Remnants travel to liver where LDL receptors on heptaocytes binds apoE and the remnant resulting in endocytosis and metabolism of the remnant

Question 14

VLDL’s transport fat made in the liver, they also deliver them by binding binding to LPL on liver and muscle cells, what apolipoproteins are added to VLDL’s ?

Answer 14

apoB100 during formation

apoC and apoE from HDL particles in the blood

Question 15

What are fatty acids released from any of these lipoproteins used for in the

a) muscle
b) adipose tissue

Answer 15

a) energy production

b) re-synthesis of triglyceride and storage as fat

Question 16

As VLDL particles are depleted they can dissociate from LPL and go back to the liver, as they deplete to 30% they become IDL’s and then to 10% LDL’s. What do IDL’s lose to become LDL’s and are endocytosed by peripheral cells

Answer 16

apoC and apoE - explanation - this means they can no longer be cleared by the liver

Question 17

What is the primary function of LDL’s?

Answer 17

To provide cholesterol from the liver to perihperal tissues

Question 18

Why are LDL’s considered more dangerous?

Answer 18

They have a much higher half life in the plasma, this means that they are in the blood for longer and thus more susceptible to oxidative damage

Question 19

How does oxidative damage to LDL’s lead to atherosclerosis?

Answer 19

Oxidised LDL’s are phagocytosed by macrohpages which results in the formation of foam cells -> fatty streak formatino -> atherosclerotic plaque formation -> atherosclerosis -> angina/stroke etc.

Question 20

Why do we see fatty liver in patients with kwashiokor

Answer 20

Low protein diet means that lipoproteins can’t be made effectively, fats not delivered to tissues and instead retained in the liver

Question 21

cells requiring cholesterol express what receptor on their surface?

Answer 21

LDL receptor- apoB-100 on LDL acts as the ligand for this

Question 22

Nascent HDL’s accumulate cholesterol and phospholipids lining blood vessels, transfer to HDL’s requires enzymatic activity, true or false?

Answer 22

False, it does not require enzymatic activity

Question 23

HDL’s collect cholesterol via reverse cholesterol uptake and deliver to the liver for breakdown to bile salts, they can also exhange cholesterol with LDL’s in circulation, and give to cells that need extra cholesterol T/F

Answer 23

T

Question 24

What is a hyperlipoproteinaemia?

Answer 24

Raised plasma level of one or more lipoprotein classs

Question 25

What causes hyperlipoproteinaemias?

Answer 25

Over-production or under-removal of the lipoproteins

Question 26

A patient presents with chylomicrons in their plasma after fasting for 10 hours, what is defective?

Answer 26

LPL - they aren’t being depleted of their cargo (type 1 hyperlipoproteinaemia)

Question 27

A patient presents with raised IDL and chylomicron remnant levels, what is causing this?

Answer 27

Defective apoE for removal in the liver

Question 28

Clinical signs of hyperlipoproteinaemias are the result of cholesterol depositions in the body because of subsequent elevated cholesterol levels, name two of these clinical signs

Answer 28

Xanthelasma - yellow patches on eyelids
Tendon Xanthoma - Nodules on tendons
Corneal arcus - white circle around eye in younger people (present in normal older people)

Question 29

give a non-pharmacological and a pharmacological approach to treating hyperlipoproteinaemias

Answer 29

non - Low cholesterol diet/ increase exercise/ stop smoking

pharm - bile salt sequesterants - forces live to make more bile acids which uses cholesterol/statins