Chloesterol and Lipid Metabolism

Question 1

are lipids soluble in water?

Answer 1

insoluble/sparingly soluble

Question 2

what are some of the functions of lipids?

Answer 2

essential for cell membrane makeup

energy

Question 3

polar/non-polar lipds are transported in the blood within liproproteins?

Answer 3

non-polar

Question 4

cholesterol and triglycerides are examples of what type of lipids?

Answer 4

non-polar

Question 5

Name the 2 common lipoproteins commonly transported within the blood?

Answer 5

HDL, LDL

Question 6

What are the levels like in LDL and HDL in cardio disease?

Answer 6

elevated LDL (or particles rich in triacylglycerols; TAGs)
decreased HDL

Question 7

Name the constituents of the lipoproteins

Answer 7

hydrophobic core
hydrophilic coat
apoproteins

Question 8

What does the hydrophobic core of lipoproteins contain?

Answer 8

esterified cholesterol and triacylglycerols (TAGs)

Question 9

What does the hydrophilic coat of lipoproteins contain?

Answer 9

monolayer of amphipathic cholesterol, phospholipids and some apoproteins

Question 10

What allows lipoproteins to bind to cells?

Answer 10

apoproteins being recognised by receptors in the liver and other tissues

Question 11

What are the apoproteins in HDL?

Answer 11

apoA1 + apoA2

Question 12

What are the apoprotein(s) in LDL?

Answer 12

apoB100

Question 13

What is the apoprotein in VLDL?

Answer 13

apoB100

Question 14

What are the chylomicrons’ apoproteins?

Answer 14

apoB48

Question 15

What do apoB containing lipoproteins do?

Answer 15

deliver triglycerides to muscle for ATP biogenesis and to adipocytes for storage

Question 16

Where are Chylomicrons formed?

Answer 16

intestinal cells

Question 17

What apoB lipoprotein transports dietary triglycerides and via which pathway?

Answer 17

chylomicrons and exogenous pathway

Question 18

Where are VLDL particles formed?

Answer 18

liver cells

Question 19

What apoB lipoprotein transports triglycerides synthesised in that organ and via which pathway?

Answer 19

VLDL

endogenous pathway

Question 20

Describe the vague 3 steps in the life cycle of lipoproteins

Answer 20

Assembly > Intravascular metabolism > Receptor Mediated Clearance

Question 21

In the assembly of Chylomicrons what does the digestion of dietary fat lead to?

Answer 21

triglycerides +cholesteryl ester into enterocyte

Question 22

Where are enterocytes converted into chylomicrons?

Answer 22

Endoplasmic Reticulum

Question 23

How are VLDL particles assembled in the liver?

Answer 23

from free fatty acids derived from adipose tissue (particularly during fasting) and de novo synthesis

Question 24

How do chylomicrons and VLDL become activated?

Answer 24

by the transfer of apoCII from HDL particles

Question 25

What happens once Chylomicrons and VLDL are activated?

Answer 25

Lipoprotein lipase then binds to them at the vascular wall via the apoCII and this then allows the breakdown into fatty acids and monoglycerides.

Question 26

Describe the Intravascular Metabolism of apoB-containing Lipoproteins?

Answer 26

LPl binds to them via apoCII hydrolyses core triglycerides to free fatty acids leaving Chylomicron and VLDL remnants

Question 27

Describe how apoB-containing lipoproteins are cleared from the body?

Answer 27

dissociated from LPL, apoE replaces apoCII and is a receptor for mediateing clearance to the liver
hepatic lipase metabolises them
think apoEXIT

Question 28

What is ‘BAD’ cholesterol?

Answer 28

LDL

Question 29

Describe how LDL cholesterol forms atheromatous plaque with a fibrous cap?

Answer 29

Dysfunction and injury of lining (endothelium) of blood vessels.

• uptake of LDL from into the intima, oxidised to atherogenic oxidised LDL (OXLDL)
• Monocytes migrate across endothelium into the intima where they become macrophages
• Uptake of OXLDL by macrophages converts them to cholesterol laden foam cells that form a fatty streak.
• Release of inflammatory substances from various cell types causes division and proliferation of smooth muscle cells into the intima causing collagen deposition.
• Atheromatous plaque forms with a fibrous cap.

Question 30

Why is HDL deemed good

Answer 30

removes excess cholesterol from cells by transporting it in plasma to the liver and it is the only thing that can eliminate cholesterol by secreting it into bile

Question 31

What is the only organ that can process cholesterol?

Answer 31

the liver

Question 32

What can reduce LDL by up to 60%? How?

Answer 32

statins
competive inhibitors of HMG CoA reductase rate limiting step in cholestorl synthesis in hepatocytes in the LIVER.
The decrease in hepatocyte cholesterol synthesis causes a compensatory increase in LDL receptor expression and enhanced clearance of LDL

Question 33

How and when are statins administered and what do they do apart from decrease LDL?

Answer 33

orally at night
decrease inflammation
reverses endothelial dysfunction
decreases thromvosis

Question 34

What is a bad side effect of statins?

Answer 34

muscle necrosis

Question 35

What do Fibrates do?

Answer 35

decreases triglycerides in 1st line

agonist of PPAR alpha which enhances the transcription of Lipoprotein lipase

Question 36

Name 2 fibrates

Answer 36

bezafibrate

gemfibrozil

Question 37

Name 3 bile acid binding resins

Answer 37

colestyramine
colestipol
colsevelam

Question 38

How do bile acid binding resins work?

Answer 38

bind to bile salts preventing them from being reabsorbed this means that more cholesterol is picked up from the blood resulting in decreased levels of hyperlipidaemia(containing cholesterol) so preventing more cholesterol absorption.
cause decreased absorption of triglycerides and increased LDL receptor expression.

Question 39

What does the drug Ezetimibe do?

Answer 39

inhibits NPC1L1 transport protein in enterocytes of duodenum, reducing absorption of cholesterol, decreasing LDL.