Lipid Transport Disorders

Question 1

Which one of hte following findings is not assocaited with chylomicronemia?
A. Creamy supernatant in blood
B. Eruptive xanthomas
C. Hepatosplenamegaly
D. Lipemia retinalis
E. Tendon xanthomas

Answer 1

E. Tendon xanthomas

Question 2

What is the hallmark blood finding in chylomicronemia?

Answer 2

↑↑↑ triglycerides in blood
- this can induce pancreatitis, but also pancreatitis can cuase ↑TG which is important clinically
- if TG is very high in blood you will get layer of fat in fridge (can be 20%)
- blood can look milky
high levels of chylomicrons as well

must be fasting

Question 3

Which proteins can be effected by chylomicronemia?

Answer 3

ApoC II
LPL
ApoC V

Question 4

Which condition is associated with recurrent pancreatitis?

Answer 4

chylomicronemia
acute pancreatitis is more like a stabbing knife pain that refers to the back. Recurrent is more like smoldering and can be a pain that people just deal with.
leads to calcificaiton of the pancreas

Question 6

Patients presents with…

LDL chlesterol = 350 g/dL
tendon xanthomas
Your patient’s defect of cholesterol metabolism is most likely caused by what mechanism?

Answer 6

Defective gene for synthesis or assembly of LDL receptors

Familial Hypercholesterolemia

Question 7

Apolioprotein B (apoB) is very important to normal cholesterol metabolism. What is a good way to describe the phenotype in patients with apoB defect?

Answer 7

These patients have a variable phenotype ranging from few clinical signs to familial hypercholesterolemia

Question 8

Which one of the following is not included in the clinical measurement of “non-HDL cholesterol”?
A. Cholesterol in IDL
B. Cholesterol in LDL
C. Cholesterol in Lp(a)
D. Cholesterol in plasma membrances
E. Cholesterol in VLDL

Answer 8

D. Cholesterol in plasma membrances

Question 9

Which one of the following findings is not expected in patietns with familial hypercholesterolemia?
A. Atherosclerosis
B. Lipemia retinalis
C. Recurrent pancreatitis
D. Tendon xanthomas
E. Xanthelasmas

Answer 9

C. Recurrent pancreatitis

Question 10

Your started your patient on orlistat and he now complains of diarrhea and incontenence. Which enzyme has been inhibited?

Answer 10

Pancreatic lipase
Orlistat is an inhibitor of pancreatic and gastric lipases. Can be effective in some patients recalcitrant to fibrates which activate peroxisome peroxisome
proliferator-activated receptor α (PPARα) that results in the lowering
plasma TG and increasing HDL

Treatments for PRIMARY HYPERTRIGLYCERIDEMIAS such as chylomicronemia

Question 11

Familial hypercholestrolemia is caused by a genetic deficiency of…

Answer 11

LDL receptors

Question 12

Which receptor on the liver cell takes up Apolipoprotein B?

Answer 12

LDL receptor

Question 13

Which receptor on the liver cell takes up Apolipoprotein E?

Answer 13

Remnant receptor
ApoE is attached to IDL and Chylomicron Remnant and allows them both to enter the liver through the LDL Receptor Related Protein (LRP)/Heparin Sulfate Proteon Glycin (HSPG)

Question 14

Which receptor on the liver cell takes up HDL particles?

Answer 14

SR-B1 (Scavenger Receptor Class B1)

Question 15

What is the site of action for ezetimibe?

Answer 15

Niemann-Pick C1 like protein
ezetimibe acts to lower cholesterol uptake by blocking the absoprtion meechanism of micelles
In the intestinal lumen, cholesterol is emulsified to form micelles, which are
taken up by mucosal cells through a poorly defined transport mechanism at the brush border involving a protein
called NPC1L1 (Niemann-Pick C1-like 1 protein)

Question 16

What is the site of action for statins?

Answer 16

HMG-CoA Reductase
Statins are HMG-CoA reductase inhibitors.
They work by competing for binding with HMG based on similarity of chemical structure. Inhibition of
de novo cholesterol synthesis results in the up-regulation of LDL receptor synthesis via the SREBP-mediated
pathway discussed earlier with the net result is the lowering of plasma LDL level

Question 17

What is the site of action of plant stanol/sterol?

phylosterols

Answer 17

Biliary micelles
Plant sterols (phytosterols) and excessive mucosal cellular cholesterol are transported back into the intestinal
lumen through ATP-dependent transporter encoded by the genes ABCG5/ABCG8.
Phytosterols, found in margarines and vegetable oil spreads and salad dressings containing esters of plant sterols, have been shown to reduce plasma cholesterol level. The exact mechanism is likely
to be complicated, but may involve competition for uptake, increased ABCG5/ABCG8 activity, displacement of cholesterol from the micelles or
inhibition of esterification by ACAT.

Question 18

Choose from the list of proteins an inactivating mutation or polymorphism associated with chylomicronemia.
A. ABC A1
B. Apolipoprotein E
C. LDL receptor
D. Lipoprotein lipase
E. Microsomal transfer protein

Answer 18

D. Lipoprotein lipase

Question 19

Choose from the list of proteins an inactivating mutation orpolymorphism assocaited with familial hypercholesterolemia.
A. ABC A1
B. Apoliprotein E
C. LDL receptor
D. Lipoprotein lipase
E. Microsomal transfer protein

Answer 19

C. LDL receptor

Question 20

Choose from the lsit of proteins an inactivating mutation or polymorphism associated with Tangiers disease.
A. ABC A1
B. Apolipoprotein E
C. LDL receptor
D. Lipoprotein lipase
E. Microsomal transfer protein

Answer 20

A. ABC A1

Question 21

Tangier’s Disease

Answer 21

ABCA-1 is an efflux protein on macrophages that allows cholesterol and cholesterol esters to leave macrophages and be picekd up by HDL.
This is an efflux disorder and is an issue with the Reverse Pathway.
Increased risk of heart disease.
Autosomal Recessive