Lipid Metabolism, Dyslipidemias and Treatment 1

Question 1

1. Explain the role of lipoproteins in atherogenesis

Answer 1

LDL is essential for the formation of atheroma, their migration into the sub endothelial space and subsequent modification and phagocytosis by macrophages leads to the inflammatory response seen in atheroma formation.

Question 2

1. Why are lipoproteins important in understanding coronary heart disease?

Answer 2

dylipidemia is one of the risk factors for CHD, and it shows a positive correlation with the risk of CHD mortality; adult humans experience contextually high levels of blood lipids and lipoproteins which leads to disease

Question 3

2. Contrast lipoprotein and lipoprotein particle.

Answer 3

lipoprotein particles are spherical with a nonpoloar TG and cholesterol esters coated in polar unesterified cholesterol, phospholipids and apolipoproteins (plasma lipids circulate in lipoprotein particles)

apoplipoprotins stabilize lipoprotein particles, impart solubility to lipoproteins, catalyze changes in particle composition and facilitate entry/exit into/from cells

Question 4

3. Explain the difference between lipoproteins and lipids.

Answer 4

lipids are the molecules that are carried inside lipoprotein particles, cholesterol and TG are lipids and once they are combined with apoplipoproteins, they are considered a lipoprotein particle

Question 5

Describe a chylomicron.

Answer 5

very low density lipoprotein made of mostly triglycerides (90-96%) that are traveling from the gut in the blood stream, they carry apoplipoproteins B-48 (coming from the intestine) and CII (activator of lipoprotein lipase)

Question 6

Describe VLDL.

Answer 6

a very low density lipoprotein made of 60% triglycerides and carrying the apoproteins B-100 (made in the liver), E and C-II

Question 7

Describe IDL.

Answer 7

intermediate density lipoprotein (need not know anything more)

Question 8

Describe LDL.

Answer 8

low density lipoprotein that is made of 50% cholesterol, carries the B-100 apoplipoprotein (made in the liver)

Question 9

Describe HDL.

Answer 9

high density lipoprotein, containing only 20% cholesterol and apoplipoprotein A-I and A-II

Question 10

Atherogenicity is determined by the _____ and ______ of lipoproteins.

Answer 10

concentration and the size

Question 11

Explain why all abnormalities in plasma lipid concentrations “dyslipidemias” are really “dyslipoporteinemias.”

Answer 11

lipids (cholesterol, tryglycerides) are only surrogate markers for lipoproteins

Question 12

HDL cholesterol, LDL cholesterol and triglycerides are surrogate measures for what?

Answer 12

HDL- C: surrogate for number of HDL particles
LDL-C: surrogate for LDL particles (usually calculated using the Friedewald equation)
TG: surrogate for number of VLDL particles

Question 13

Under what circumstances can the LDL measure be misleading/ inaccurate as calculated by Friedewald equation?

Answer 13

less accurate as TG levels increase, since the assumption that TG/5= VLDL-C breaks down

misleadingly low when small LDL particles are present

Question 14

At the same level of LDL-C, people with small, dense LDL have about ____ more particles than those with large LDL.

Answer 14

25%

Question 15

Explain why the size of lipoprotein particles is important.

Answer 15

Large LDL and HDL particles can carry more cholesterol than small LDL and HDL particles, the problem arises with increasing number of lipoprotein molecules, not necessarily with increasing total cholesterol (although there is a vague correlation)

the number of LDL particles interacting with the arterial wall drives the disease, not the the cholesterol within, the size of LDL particles modulates the risk

Question 16

4. Explain the key steps in the endogenous lipoprotein pathway involving lipids from the gut.

Answer 16

1. lipids from the gut are transported in a chylomicron (with apo B48, apoC and apo E
2. chylomicron undergoes lipolysis by LPL creating a HDL and chylomicron remnant (IDL)
3. chylomicron remnant can be cleared from the body by the liver via remnant receptor binding

Question 17

4. Explain the key steps in the endogenous lipoprotein pathway involving lipids from the liver.

Answer 17

1. liver produces VLDL with apo B-100, apo C and apo E
2. lipolysis by LPL creates an IDL which is metabolized by hepatic triglyceride lipase into LDL
3. LDL can be taken up by the liver via LDL receptors or be deposited in tissues.

Question 18

Apo B, E, and B/E receptors are all the same receptor, they are also know by the following names:

Answer 18

LDL and chylomicron remnant receptor

Question 19

Cholesterol from the diet and bile enters the small intestine and is absorbed via a ______ _____ .

Answer 19

sterol transporter (unabsorbed cholesterol is excreted in the feces)

Question 20

Chylomicron remnants, LDL and IDL are taken up by the hepatic ______ receptor (CYM, LDL) or ______ receptor related protein. (CYM, IDL)

Answer 20

LDL receptor, or to a lesser extent LDL receptor-related protein

Question 21

Excess cholesterol that is delivered to back to the liver via HDL particles, which are taken up by hepatic ____.

Answer 21

SR-BI

Question 22

4. Bile is reabsorbed in the intestine by ____ ___ ____ transporter. After absorption some cholesterol can be exported back from the enterocyte into the intestinal lumen by the _____ transporter (_____)

Answer 22

intestinal bile acid transporter; ABC transporter (ABCG5/G8

Question 23

4. Within enterocytes, cholesterol is esterified with fatty acids via ____-___ _____ _____ and absorbed fatty acids are also used to synthesize ___ ___ and ___ in the enterocyte.

Answer 23

acyl-CoA cholesterol acyltransferase (ACAT)

TG and phospholipids

Question 24

Through the activity of __ ____ ____ cholesterol esters are packaged with TG phopholipids and apolipidprotein B-48 into chylomicrons.

Answer 24

microsomal transfer protein (MTP)

Question 25

Chylomicrons acquire apo E and apo CII during transport to the liver, these apoplipoproteins are required for what actions of the lipoprotein particle?

Answer 25

LPL of endothelial cells requires apoC to hydrolyze TG
chylomicron remnants are cleared from the circulation by binding of apo E to to the hepatic LDL receptor or LDL receptor related protein (some evidence that they can also be taken up by the aerial wall where they can contribute to atherogenesis)

Question 26

How are LDL formed?

Answer 26

LDL are formed from the depletion of TG from IDL due to hydrolysis by LPL (apoC and a poE play similar roles in the metabolism of chylomicrons and VLDL)

Question 27

Cholesterol leaves the liver via 2 routes, name them

Answer 27

secretion in the form of VLDL (most of which is returned to the liver in the form of LDL)
excretion into the bile

Question 28

The liver controls cholesterol balance by regulating two things, name them.

Answer 28

regulating excretion of cholesterol into the bile
regulating the amount of cholesterol that is taken up by altering LDL receptors

(50% of body pool cleared daily)

Question 29

How are levels of LDL receptor expressed altered?

Answer 29

regulated by diet, hormones, genetics, medications

expression suppressed by cellular cholesterol, stimulated by cholesterol depletion, insulin and T4

Question 30

Cholesterol is created inside cells via what enzyme?

Answer 30

HMG-CoA Reductase