Cholesterol Synthesis and Lipoprotein Transport

Question 1

What is the structure of cholesterol?

Answer 1

27 carbons, 4 rings, planar, one side hydrophobic, one side hydrophilic (because of hydroxyl group at carbon 3)

Question 2

What are the properties of cholesterol?

Answer 2

waxy, steroid metabolite that is insoluble in water

Question 3

Where is cholesterol commonly found in the body?

Answer 3

In atherosclerotic plaques and gall stones

Question 4

Where is cholesterol made?

Answer 4

In the liver

Question 5

What are the three fates of cholesterol?

Answer 5

Stored in the liver, bile or in membranes

Question 6

How is is stored in the liver?

Answer 6

As a cholesteryl ester (enzyme ACAT removed hydroxyl group)

Question 7

Why is cholesterol required in membranes?

Answer 7

Because phospholipid have cis bond kinks making the membrane too fluid - 8% cholesterol fills these gaps and makes the membrane the right level of solidness at 37 degrees

Question 8

How is cholesterol synthesised?

Answer 8

Acetyl CoA goes to acetoacetyl CoA which goes to HMG CoA which goes to mevalonic acid (using 2NADPH and HMG-CoA reductase), mevalonic acid goes to cholesterol

Question 9

What is the feedback mechanism in the pathway?

Answer 9

Cholesterol negatively feedbacks to HMG CoA reductase

Question 10

What are the intermediates in the conversion of mevalonic acid to cholesterol?

Answer 10

Squalene and isoprene

Question 11

Where does acetyl CoA come from?

Answer 11

Mitochondria - from glucose or fatty acid metabolism

Question 12

How does acetyl CoA get from the mitochondria to the cytosol?

Answer 12

Converts to citrate via the Krebs cycle which can pass through the membrane and then the reverse Krebs cycle is used to convert it back to acetyl CoA

Question 13

What are lipoproteins?

Answer 13

A phosopholipid monolayer sphere with a hydrophobic inside filled with cholesterol and triacylglyerols

Question 14

What kinds of lipoproteins are there?

Answer 14

chylomicrons, VLDL, LDL and HDL

Question 15

What are chylomicrons?

Answer 15

A lipoprotein package formed from dietary fats that allows them to be transported in circulation

Question 16

What is apoB-100?

Answer 16

The pure protein part of the lipoprotein - recognised by receptors on the liver

Question 17

Which lipoprotein contains the most cholesterol?

Answer 17

LDL

Question 18

Which lipoprotein contains the most triacylglycerols?

Answer 18

chylomicrons

Question 19

What lipoprotein is ApoA-I associated with?

Answer 19

HDL

Question 20

What is the role of ApoA-I?

Answer 20

activates the enzyme LCAT

Question 21

What lipoproteins in ApoC-II associate with?

Answer 21

chylomicrons, VLDL, HDL

Question 22

What is the role of ApoC-II?

Answer 22

Activates the enzyme lipoprotein lipase so that tissues can use fat as an energy source

Question 23

Which lipoprotein is the scavenger?

Answer 23

HDL

Question 24

Which lipoprotein is the donor?

Answer 24

LDL

Question 25

Where do VLDL come from?

Answer 25

The liver

Question 26

What happens to chylomicrons after they have been stripped of their free fatty acids in circulation by tissues with ApoC-II?

Answer 26

The remnants are transported back to the liver to be recycled

Question 27

What happens to VLDLs after they have been stripped of their free fatty acids in circulation by tissues with ApoC-II?

Answer 27

The remnants (also called IDL) are either transported back to the liver for recycling or can be converted to LDL

Question 28

Where does LDL go?

Answer 28

To extrahepatic tissue (e.g. the arteries) to deposit cholesterol

Question 29

Where do HDL precursors come from?

Answer 29

The liver and intestine

Question 30

What does HDL do?

Answer 30

Goes to the cholesterol deposits made by LDL and scavenge the cholesterol and take it back to the liver to be recycled

Question 31

What is the role of LCAT?

Answer 31

It is an enzyme in the plasma activated by ApoA-I that converts cholesterol into an ester to become part of HDL

Question 32

What is the role of ACAT?

Answer 32

It is an enzyme in the liver that converts cholesterol into an ester to from a VLDL

Question 33

What is the structure of HDL?

Answer 33

Two circular protein molecules surround cholesterol and phospholipids

Question 34

What is the upper limit of cholesterol recommended by the national heart foundation?

Answer 34

5.5mmol/L

Question 35

How is atherosclerosis formed?

Answer 35

LDL accumulates in an artery wall, endothelial cells in the artery react by displaying adhesion molecules, white cells invade the tissue and secrete inflammatory mediators, macrophages digest LDLs and become engorged with cholesterol and become foam cells, fibrous tissue develops to trap the foam cells, foam cells produce tissue factor and if the fibrous cap breaks a blood clot can form

Question 36

What is familial hypercholesterolaemia?

Answer 36

An inherited dominant disorder of mutations in the LDL receptor - affects 1/500 in the heterozygous form and 1/million in the homozygous form

Question 37

What are xanthomas?

Answer 37

Cholesterol deposits - waxy plaques beneath the skin in untreated familial hypercholesterolaemia

Question 38

How is familial hypercholesterolaemia treated?

Answer 38

With HMG CoA reductase inhibitors - statins

Question 39

Who won the nobel prize for the development of statins?

Answer 39

Michael Brown and Joseph Goldstein in 1985

Question 40

What is an adverse effect of statins?

Answer 40

Depleted Q10