Lipoprotein Metabolism

Front 1

a. Where are chylomicrons formed?

Back 1

i. Intestinal epithelial cells
ii. Assembled in Golgi apparatus

Front 2

b. Where are nascent chylomicrons secreted?

Back 2

i. Into lymph
ii. apoA proteins
iii. apoB-48

Front 3

c. What do chylomicrons accumulate in the blood stream?

Back 3

i. apoC and apoE from HDL

Front 4

d. What is LPL’s effect on chylomicrons?

Back 4

i. Removes TAG-- chylomicrons become smaller

Front 5

e. How are phospholipids transferred to HDL?

Back 5

i. PLTP

Front 6

f. What components of chylomicrons are transferred to HDL?

Back 6

i. Surface molecules→
1. Phospholipid
2. Cholesterol
3. apoA and apoC

Front 7

g. After losing its surface components, what do chylomicrons gain from HDL?

Back 7

i. More apoE
ii. Cholesteryl ester

Front 8

h. What clears chylomicron remnants from blood?

Back 8

i. LDL binds apoE
ii. LRP
iii. Both in liver

Front 9

i. When are chylomicrons present in the blood?

Back 9

i. After a meal
ii. ½ life is less than 1 hours

Front 10

j. What is the distribution of chylomicrons to the body tissues?

Back 10

i. 80% to heart, adipose and muscle
ii. 20% to liver

Front 11

a. Where are VLDL and LDL synthesized?

Back 11

i. Liver

Front 12

b. What are the steps of VLDL and LDL synthesis?

Back 12

i. Lipids assembled in ER
ii. Apoproteins synthesized in RER
iii. VLDL assembled in Golgi
iv. Secreted into bloodstream as nascent VLDL

Front 13

c. What does VLDL acquire from HDL in the bloodstream?

Back 13

i. apoC
ii. apoE

Front 14

d. What removes TAGs from VLDL?

Back 14

i. LPL

Front 15

e. What causes VLDL to become smaller?

Back 15

i. apoC, phospholipids, and TAGs transferred to HDL

Front 16

f. What do VLDL remnants acquire in the bloodstream?

Back 16

i. Choelsteryl ester

Front 17

g. How is VLDL/IDL removed from the bloodstream?

Back 17

i. LDL (B100/E) receptor in liver
ii. 50% of IDL cleared by liver

Front 18

h. What happens to the 50% of IDL not cleared by the liver?

Back 18

i. It is converted to LDL
ii. Becomes anchored to HL→ removal of TAG and phospholipids
iii. ApoE is transferred to HDL

Front 19

i. How many molecules of apoB100 does LDL contain?

Back 19

i. 1

Front 20

j. What is the half-life of plasma LDL?

Back 20

i. Up to several days

Front 21

k. How is LDL cleared from the blood?

Back 21

i. LDL receptor
ii. LRP receptor
iii. In liver (70%)

Front 22

l. What clears the 30% of LDL not cleared by the liver?

Back 22

i. Adrenal and gonads-- LDL scavenges cholesterol for steroid hormones
ii. Macrophages

Front 23

a. Where is HDL synthesized?

Back 23

i. Liver and intestine

Front 24

b. What are the characteristics of nascent HDL?

Back 24

i. Disc-shaped
ii. Phospholipid rich

Front 25

c. What are the apoproteins of nascent HDL from the liver?

Back 25

i. AI
ii. AII
iii. apoE
iv. apoC

Front 26

d. What are the apoproteins of nascent HDL from the intestine?

Back 26

i. AI

Front 27

e. What does HDL acquire in the bloodstream?

Back 27

i. Cholesterol from outer leaflet of cells by ABCA1
ii. LCAT from plasma
iii. CETP from plasma
iv. Other apoproteins/lipoproteins

Front 28

f. How does HDL dock to other cells?

Back 28

i. apoAI
ii. apoE

Front 29

g. How is HDL involved in reverse cholesterol transport?

Back 29

i. HDL3 expresses a high LCAT activity
ii. LCAT removes cholesterol, converting it to cholesteryl ester
iii. HDL3 transfers CE to IDL and chylomicron remnants in exchange for phospholipid and TAGs

Front 30

h. How does HDL3 become HDL2?

Back 30

i. Acquiring more phospholipids and increasing in size through reverse cholesterol transport

Front 31

i. For what is HDL2 a substrate?

Back 31

i. HL→ hydrolyzes excess TAG and PL

Front 32

j. How do SRB1 and HDL2 interact? What is the result of this interaction?

Back 32

i. SRB1 of liver binds HDL2 and selectively transfers CE to liver cell
ii. HDL3 is regenerated from HDL2 in this manner

Front 33

a. What causes abetalipoproteinemia?

Back 33

i. Deficiency of a TAG transfer protein in ER
ii. Liver and intestine unable to assemble or secrete apoB-containing lipoproteins

Front 34

b. What is absent in abetalipoproteinemia?

Back 34

i. Chylomicrons
ii. VLDL
iii. LDL

Front 35

c. What are the consequences of abetalipoproteinemia?

Back 35

i. Severe fat malabsorption
ii. Accumulation of TAGs in intestine and liver
iii. Deficiencies of fat soluble vitamins

Front 36

d. What will untreated patients of abetalipoproteinemia develop?

Back 36

i. Ataxia
ii. Retinitis pigmentosa
iii. Myopathy

Front 37

a. How do you tx abetalipoproteinemia?

Back 37

i. Vitamin E

Front 38

f. What causes Tangier disease?

Back 38

i. Deficiency of ABCA1

Front 39

g. What are the consequences of Tangier disease?

Back 39

i. HDL cannot be formed
ii. Decreased LDL
iii. Cholesteryl ester deposits in RES, bone marrow, and Schwann cells

Front 40

h. What are the symptoms of Tangier disease?

Back 40

i. Peripheral neuropathy
ii. Hepatosplenomegaly
iii. LAD
iv. Mild tendency for early atherosclerosis

Front 41

i. What is the cause of familial hypercholesterolemia?

Back 41

i. Deficiency of LDL receptor

Front 42

j. What is the average cholesterol level in familial hypercholesterolemia?

Back 42

i. 350 mg/dL

Front 43

k. What form of inheritance is more common in familial hypercholesterolemia?

Back 43

i. Heterozygotes→ more severe form of disease

Front 44

l. What are the consequences of familial hypercholesterolemia?

Back 44

i. Accelerated CHD
ii. Homozygotes die by age of 20

Front 45

m. What causes xanthomas?

Back 45

i. Mutations in LDL receptor

Front 46

n. What are the consequences of familial LCAT deficiency?

Back 46

i. Block in reverse cholesterol transport
ii. Limited ability of HDL to acquire cholesterol from VLDL or chylomcirons
iii. Elevated blood cholesterol and TAGs

Front 47

o. What are the symptoms of familial LCAT deficiency?

Back 47

i. Free cholesterol accumulates in most tissues
ii. Kidney disease
iii. Corneal clouding
iv. Mild tendency for early atherosclerosis

Front 48

p. What are the consequences of a CETP deficiency?

Back 48

i. Benign
ii. Cholesteryl esters cannot be transferred from HDL to other lipoproteins
iii. Homozygotes have 4x elevation of HDL cholesterol
iv. LDL is normal or low

Front 49

q. How is reverse cholesterol transport still possible in someone with a CETP deficiency?

Back 49

i. SRB1 receptors of liver
ii. Endocytosis of HDL with multiple copies of apoE

Front 50

a. What is the plasma lipid profile of type I hyperchylomicronemia?

Back 50

a. Greatly increased TAGs
b. Cholesterol slightly elevated
c. Not associated with increased atherosclerosis

Front 51

b. What causes type I hyperlipoproteinemia?

Back 51

a. LPL deficiency
b. apoC-II deficiency

Front 52

c. What are the symptoms of type I hyperlipoproteinemia?

Back 52

a. Eruptive xanthomas
b. Abdominal pain after a fat-containing meal
c. Recurrent pancreatitis

Front 53

d. What is the manifestation of type II hypercholesterolemia?

Back 53

a. LDL elevation
b. Atherosclerosis is a major risk

Front 54

e. What causes type II hypercholesterolemia?

Back 54

a. Familial hypercholesterolemia
b. Obesity, diabetes (less common)

Front 55

f. What is the plasma lipid profile of type III dysbetalipoproteinemia?

Back 55

a. Increased TAGs
b. Increased cholesterol

Front 56

g. What causes type III dysbetalipoproteinemia?

Back 56

a. Homozygotes for apoE2
b. ApoE2 does not bind hepatic apoE receptors
c. Chylomicrons and VLDL remnants accumulate

Front 57

h. What are the symptoms of dysbetalipoproteinemia?

Back 57

a. Xanthomas
b. Increased risk of CHD

Front 58

i. How do you tx dysbetalipoproteinemia?

Back 58

a. Dietary changes

Front 59

a. What is the plasma lipid profile of type IV/hypertriglyceridemia?

Back 59

a. Increased TAGs
b. Hypercholesterolemia due to cholesterol content of VLDL

Front 60

k. What causes type IV/hypertriglyceridemia?

Back 60

a. Obesity
b. Type II diabetes
c. Progesterone-rich contraceptives
d. Excess dietary carbohydrates

Front 61

l. What is the plasma lipid profile of type V/hyperlipoproteinemias?

Back 61

a. Increased TAGs
b. Increased cholesterol

Front 62

m. What is the cause of type V/hyperlipoproteinemias?

Back 62

a. Increased chylomicrons and VLDL
b. Associated with uncontrolled diabetes, obesity, and kidney disease

Front 63

n. How do you tx type V/hyperlipoproteinemias?

Back 63

a. Dietary changes