Chemical Pathology - Lipoprotein metabolism, CVD and obesity

Question 1

What is the role of HDL?

Answer 1

Picks up excess cholesterol from the periphery and transports it to liver

Question 2

What is the role of the enzyme CETP in cholesterol metabolism?

Answer 2

movement of cholesterol from HDL to VLDL conversion
movement of triglyceride from VLDL to HDL

Question 3

What is the key enzyme involved in cholesterol synthesis?

Answer 3

HMG CoA reductase

rate determining step that converts HMG Coa to mevalonate in the synthesis of cholesterol

Question 4

Which enzyme converts cholesterol to cholesteryl ester?

Answer 4

ACAT

Acyl-coenzyme A:cholesterol acyltransferases

Question 5

What is VLDL constituted of?

Answer 5

ApolipoproteinB, cholesteryl ester and triglyceride

Question 6

What is the function of 7-alpha hydroxase in cholesterol metabolism?

Answer 6

Converts cholesterol to bile acids

Question 7

What is the main component of mixed micelles?

Answer 7

Bile acids

Question 8

Where are bile acids resorbed?

Answer 8

Terminal ileum

Question 9

What controls the amount of cholesterol resorbed into the intestine?

Answer 9

Balance of 2 transporters : NPC1L1 and ABC G5/G8

NPC1L1 mediates intestinal cholesterol absorption and it may also limit hepatobiliary cholesterol excretion,

responsible for biliary and transintestinal secretion of cholesterol and dietary sterols.

Question 10

What is the inheritance pattern of familial hypercholesterolaemia type II?

Answer 10

dominant

Question 11

What name is given to an inherited predeliction to high HDL, and what mutation causes this?

Answer 11

Familial hyperalphalipoproteinaemia
= CETP deficiency

Cholesteryl ester transfer protein

Question 12

What condition is caused by ABC G5/G8 mutation?

Answer 12

Phytosterolaemia

Question 13

What is phytosterolaemia?

Answer 13

AR Inherited condition that allows plant sterols to enter the plasma freely, which are more athrogenic than cholesterol itself causing premature atherosclerosis

Question 14

Recall 3 clinical signs of hypercholesterolaemia

Answer 14

Xanthalasma
Arcus
Tendon xanthoma

Question 15

How can you examine for tendon xanthoma?

Answer 15

Feel back of ACL

Question 16

What are the different types of primary hypertriglyceridaemia? what’s the inheritance

Answer 16

I, IV and V
all dominant
characterized by the liver overproducing very-low-density lipoproteins (VLDL

Question 17

What is A-beta-lipoproteinaemia?

Answer 17

MTP deficiency causing hypolipidaemia

Inability to absorb fat results in deficiencies of lipids and various essential vitamins

Question 18

Recall 4 inherited conditions that can cause hypolipidaemia

Answer 18

A-beta-lipoproteinaemia - AR
Hypo-beta-lipoproteinaemia - AD
Tangier disease (HDL deficiency)
hypo-alpha-Lipoproteinaemia

Question 19

What is the effect of statins on cholesterol levels?

Answer 19

Very effective at reducing LDL, also reduce triglyceride and HDL

Question 20

What is the effect of fibrate drugs on cholesterol levels?

Answer 20

Very effective at reducing triglycerides,

e.g fenofibrate

also reduces LDL

Question 21

What is the role of PCSK9?

Answer 21

Binds LDLR and promotes its degradation

Question 22

What is the mechanism of action of statins?

Answer 22

HMG coA reductase inhibition

Question 23

What is the most potent pharmacological agent at reducing low density lipoprotein concentration in blood?

Answer 23

evolocumab - pcsk9 inhibitor

another pcsk9 inhibitor is alirocumab

Question 24

what enzyme converts cholesterol in liver to bile acids

Answer 24

7a hydroxylase

Question 25

what packages cholesterol esters

Answer 25

Microsomal triglyceride transfer protein (MTP)

Question 26

what packages free cholesterol from periphery into HDLs

Answer 26

ABC A1

Question 27

give 4 types of primary hypercholesterolaemia

Answer 27

Familial hypercholesterolaemia (FH) Polygenic hypercholesterolaemia Familial hyper-a-lipoproteinaemia phytosterolaemia

Question 28

give 3 mutations seen in FH

Answer 28

LDL-R apoB PCSK9

Question 29

result of a loss vs gain mutation in pcsk9

Answer 29

Gain-of-function mutations in PCSK9 have been associated to hypercholesterolemia and to an increase in cardiovascular risk. = FH! In contrast, loss-of-function mutations in PCSK9 result in low LDL-c levels and seem to decrease the risk of coronary heart disease, without having any known negative impact on human health

Question 30

what 2 proteins in implicated in familial type 1 hypertriglyceridaemia

Answer 30

apoC 2 deficiency or lipoprotein lipase def (elevated chylomicrons)

Question 31

what gene in implicated in type 5 hypertriglyceridaemia

Answer 31

apoA-V deficiency

Question 32

what is mixed hyperlipadaemia, give an example of a disease

Answer 32

characterised by raised triglyceride AND cholesterol levels familial dysbetalipoproteinemia type 3 hyperlipoproteinameia aka

Question 33

what polymorphism in type 3 Hyperlipoproteinemia/familial dysbetalipo

Answer 33

Apoe2 | (Apoe4 increases Alzheimers, ApoE2 decreases it)

Question 34

wat 2 signs are diagnostic of dysbetalipoproteinemia/type 3 Hyperlipoproteinemia

Answer 34

Yellow infiltration of the palmar creases xanthoma on the elbows.

Question 35

what mutation in hypoalphalipoproteinaemia and hypobetalipoproteinaemia

Answer 35

hypo alpha = apoA-I mutations hypo beta = truncated apoB

Question 36

mutation in ABC A1 causes

Answer 36

tangier disease mutation causes HDL def

Question 37

Tangier disease is most often characterized by

Answer 37

enlarged orange- or yellow-colored tonsils. This discoloration is due to fatty deposits accumulating in the tonsils

Question 38

state a MTP inhibitor

Answer 38

lomitapide

Question 39

give an antiPCSK9 monoclonal antibody

Answer 39

REGN727 aka Alirocumab

Question 40

give a drug that inhibits inhibits apolipoprotein B 100 (apoB) protein synthesis

Answer 40

mipomersen risk of liver damage

Question 41

give 3 drugs to treat FH

Answer 41

hetero - statins homo - mipomersen, lomitapide

Question 42

give a CVD risk marker

Answer 42

lipoprotein a an ldl

Question 43

what drug to manage high lipoprotein a

Answer 43

nicotinic acid aka niacin It is unique among the various lipid therapies in that it can not only reduce all of atherogenic lipid fractions (total cholesterol, low-density lipoprotein, very low-density lipoprotein, non-HDL lipoproteins, and triglycerides), but is also the most effective agent for raising high-density lipoprotein (specifically Apolipoprotein A-1). It is also the only lipid therapy that can lower lipoprotein (a).

Question 44

give 2 surgeries for obesity, which is better

Answer 44

billiopancreatic diversion \> gastric bypass | (both better than medical therapy)

Question 45

ezetimibe targets what

Answer 45

NPC 1L1