Chem path 2s - Lipoproteins

Question 1

Outline the structure of atherosclerotic plaques

Answer 1

A necrotic core (DEad macrophages) of cholesterol crystals surrounded by foam cells (macrophages) all topped with a fibrous cap

Question 2

What is the biggest lipoprotein?

Answer 2

Chylomicrons

Question 3

Which lipoproteins are highest in triglycerides?

Answer 3

VLDLs and chylomicrons

Question 4

Which lipoproteins are the main carriers of cholesterol?

Answer 4

LDLs

Question 5

How do we obtain cholesterol?

Answer 5

Diet & bile acids or synthesised in the liver

Question 6

What is the enzyme invovled in the transport of cholesterol across the intestinal epithelium?

Answer 6

NPC1L1

Question 7

Where are bile acids reabsorbed?

Answer 7

TErminal ileum

Question 8

What enzyme does cholesterol downregulate the activity of?

Answer 8

HMG-COA-REDUCTASE - this is the main enzyme to produce cholesterol in the liver from acetate and mevalonic acid i.e. the amount of cholesterol synthesised in the liver is dependent on the amount of cholesterol absorbed in the small intestine

Question 9

what are the two fates of cholesterol which is either made in the liver/brought to the liver?

Answer 9

1) Hydroxylation by CYP7A1 enzyme, 7a-hydroxylase –> bile acids
2) Esterified by ACAT –> cholesterol esters and combined with TG and apoB in to VLDL (precursor to LDL)

Question 10

What is the precursor to LDL?

Answer 10

VLDL

Question 11

Which enzyme is involved in packaging free cholesterol in the peripheries into HDLs?

Answer 11

ABCA1

Question 12

What does CETP mediate the movement of?

Answer 12

VLDL –> HDL

HDL –> VLDL

Question 13

Which genes can be mutated in familial hypercholesterolaemia?

Answer 13

LDLR, ApoB, PCSK9 (AD usually)

Question 14

Which primary hypercholesterolaemia results in longevity?

Answer 14

Familial hyper-alpha-lipoproteinaemia = CETP deficiency so increase in HDL

Question 15

What is the function of pCSK9?

Answer 15

Binds to LDLR and promotes its degradation

Question 16

What are loss of function PCSK9 mutations associated with?

Answer 16

Low LDL levels

Question 17

What are the three types of primary hypertriglyceridaemia?

Answer 17

Type I, V and IV

Question 18

Type I familial hypertriglyceridaemia?

Answer 18

deficiency in apoCII or lipoprotein lipase deficiency –> INCREASED CHYLOMICRONS

Question 19

Type IV familial hypertriglyceridaemia?

Answer 19

Increased TG synthesis - INCREASED VLDLs

Question 20

Type V familial hypertriglyceridaemia?

Answer 20

apoA V deficiency - INCREASED VLDLs and some CMs

Question 21

Which type of mixed primary hyperlipidaemia is associated with alzheimer’s?

Answer 21

Familial dys-beta-lipoproteinaemia - ApoE2 polymorphism. ApoE3 = normal, ApoE4 = increased Alzheimer’s risk, ApoE2 = reduced Alzheimer’s

Question 22

What is a diagnostic sign of famililal dys-beta-lipoproteinaemia?

Answer 22

Yellowing of palmar crease

Question 23

Name one example of hypolipidaemia disease

Answer 23

Tangier disease

Question 24

What is the mutation of Tangier disease?

Answer 24

ABC A1–> HDL deficiency (Features orange tonsils)

Question 25

Outline the pathophysiology of atherosclerosis

Answer 25

LDLs become oxidised once it has gone through the vascular wall
Then taken up by macrophages
Within the macrophages the LDLs become esterified and form foam cells

Question 26

Which lipid lowering drug is the best for reducing LDLs and by how much?

Answer 26

Statins - ~50% reduction in LDL

Question 27

Which drugs are best at lowering TGs?

Answer 27

Fibrates e.g. gemfibrozil

Question 28

How does ezetimibe work?

Answer 28

Blocks cholesterol absorption by inhibiting NPC1LI

Question 29

What are the three treatment options for obesity?

Answer 29

Low calorie diet + exercise
Iatrogenic malabsorption (orlistat - pancreatic lipase inhibitor)
Bariatric surgery (BMI >40kg/m2)

Question 30

What are the three types of bariatric surgery?

Answer 30

Gastric banding
Bypass (Roux-en-Y)
Biliopancreatic bypass

Question 31

What is the definition of success in bariatric surgery?

Answer 31

> 50% reduction in excess weight

Question 32

What are the advantages of bariatric surgery?

Answer 32

Reduces excess weight
Reduces T2DM risk (72%)
Reduced TGs (50-60%)
Increased HDL
Reduced fatty liver
Reduced HTN

Question 33

Which mode of bariatric surgery reduces Hba1c the most?

Answer 33

Biliopancreatic diversion > bypass > medical therapy