Cholesterol Transport (2)

Front 1

Lipoprotein with the highest number of triacylglycerides?

Back 1

Chylomicron

Front 2

Lipoprotein with the highest number of protein and phospholipid?

Back 2

HDL

Front 3

2 Roles of Apoproteins?

Back 3

1)sollubilize hydrophobic lipids
2) have cell-targeting signals

Front 4

Is the core high-density of low density in a chylomicron?

Back 4

low-density

Front 5

Is the protein surface of the chylomicron high or low density?

Back 5

high-density

Front 6

where are chylomicrons synthesized?

Back 6

intestine

Front 7

what is the major fat in our diet?

Back 7

triacylglycerols

Front 8

major enzyme that digests dietary triacylgylcerols?

Back 8

pancreatic lipases

Front 9

Where does pancreatic lipase hydrolyze triacylglycerol to FFA and 2-Monoacylglycerol?

Back 9

lumen of the intestine

Front 10

What two proteins are initially assembled on chylomicrons?

Back 10

Apo A
Apo B48

Front 11

Once in the circulation, which proteins does HDL add to the chylomicron?

Back 11

Apo CII
Apo E

Front 12

What activates lipoprotein lipase?

Back 12

Apo CII

Front 13

What binds lipoprotein lipase to the endothelial surface of the blood capillaries?

Back 13

Heparin Sulfate Proteoglycans

Front 14

HOw do FFA travel to the extrahepatic tissues?

Back 14

albumin

Front 15

What produces chylomicron remnants?

Back 15

lipoprotein lipase

Front 16

What does the liver recognize on the surface of chylomicron remnants?

Back 16

Apo E

Front 17

How does the liver take up the chylomicron remnant?

Back 17

Hepatic Lipase
LDL Receptor

Front 18

What binds to hepatocyte cell surface by Heparin Sulfate Proteoglycans?

Back 18

Hepatic Lipase- hydrolyzes triacylglycerides more

Front 19

What does the LDL receptor to with chylomicron remnant?

Back 19

targets it to the lysosome where it is degraded and cholesterol is released

Front 20

3 uses for cholesterol once released in the liver

Back 20

1)bile
2)bile salts
2)packaged into other lipoproteins

Front 21

Which proteins do VLDL and IDL have?

Back 21

Apo CII
Apo E
Apo B-100

Front 22

Where is VLDL assembled?

Back 22

liver

Front 23

what is a major role of VLDL?

Back 23

to get rid of excess triacylglycerol in liver cells

Front 24

3 ways excess triacylglycerol accumulates in the liver

Back 24

1)lipogenesis
2)plasma FFA
3)chylomicron remnants

Front 25

lipoprotein lipase breaks VLDL into?

Back 25

IDL
(VLDL remnants)

Front 26

What interacts with Apo E on IDL to make LDL?

Back 26

Hepatic Lipase

Front 27

Which lipoprotein has the most cholesteryl esters?

Back 27

LDL

Front 28

How is IDL formed from VLDL?

Back 28

a triacylglycerol is removed by lipoprotein lipase

Front 29

How is LDL formed from IDL?

Back 29

a triacylglycerol is removed by hepatic lipase

Front 30

what proteins are on the surface of LDL?

Back 30

Only Apo B-100

Front 31

What is a difference between VLDL and chylomicrons?

Back 31

VLDL already has Apo CII and Apo E on the cell surface. No need to get from HDL

Front 32

Higher percentage of cholesterol in VLDL or chylomicron?

Back 32

VLDL

Front 33

Fates of IDL

Back 33

1)LDL receptor- lysosome-free cholesterol
2)Heaptic Lipase- LDL

Front 34

Roles of LDL

Back 34

1)transport cholesterol to peripheral tissues
2) regulation of de novo synthesis at these peripheral tissues

Front 35

How does LDL bind to LDL receptor?

Back 35

Apo B-100

Front 36

Why does LDL last longer in the circulation?

Back 36

The low affinity of the Apo B-100 receptor

Front 37

What binds to the LDL receptor?

Back 37

IDL- high affinity
LDL- low affinity

Front 38

Why is HDL "good cholesterol"?

Back 38

it removes excess cholesterol from the circulation

Front 39

Proteins on HDL

Back 39

Apo A1
Apo C
Apo E

Front 40

Where does HDL originate?

Back 40

liver and small intestine

Front 41

What is the origional/oblong shape of HDL with no hydrophobic core?

Back 41

nascent/discoidal HDL

Front 42

What makes cholesterol esters on surface of spherical particle?

Back 42

LCAT (Lecithin-Cholesterol Acyl Transferase)

Front 43

What is ABCA-1?

Back 43

ATP-binding casette transporter
-delivers cholesterol to Apo-A1 forming nascent HDL

Front 44

how is nascent cholesterol formed?

Back 44

cholesterol binding to Apo A1

Front 45

what activates LCAT?

Back 45

Apo A1

Front 46

How is LCAT different from ACAT?

Back 46

ACAT is in the cell, LCAT is in the blood where it circulates with HDL

Front 47

what transfers a fatty acid into cholesterol in the blood

Back 47

Lecithin (phosphatidylcholine)

Front 48

What transfers fatty acids to cholesterol inside cells?

Back 48

Fatty Acid Acetyl CoA

Front 49

What removes lysolecithin from the blood?

Back 49

albumin

Front 50

What happens to cholesterol esters from HDL?

Back 50

transferred via CETP (cholesterol ester transfer protein) to LDL or VLDL

Front 51

what provides a substrate for LCAT?

Back 51

PLTP (Phospholipid Transfer Protein)

Front 52

What removes cholesterol esters from HDL and transfers them to IDL and LDL?

Back 52

CETP (Cholesteryl Ester Transfer Protein)

Front 53

What is the exchange that CETP does?

Back 53

gives cholesterol ester to other lipoproteins, transfers trigylcerides onto HDL

Front 54

LCAT in the plasma is preferentially associated with

Back 54

LCAT

Front 55

receptor in the liver and adrenal gland that mediates selective uptake of cholesteryl esters from HDL particles

Back 55

SR-B!
(Scavenger Receptor B1)

Front 56

What happens to HDL after it binds to SR-B1?

Back 56

depleted HDL recirculates into bloodstream to extract more cholesterol from extrahepatic tissues or other lipoprotein particles

Front 57

Oncw HLS paticle is mature, 2 things can happen

Back 57

1) CETP- loads IDL with more cholesteryl esters
2) can interact with SR-B1 receptor

Front 58

Where is the SR-B1 receptor located?

Back 58

liver and adrenal gland

Front 59

Where does HDL commonly acquire cholesterol from?

Back 59

macrophage foam cells

Front 60

What does PLTP cause HDL to take up?

Back 60

PHOSPHOLIPIDS and cholesterol

Front 61

What are the 3 things measured diagnostically for lipid levels

Back 61

1)LDL
2)HDL
3) plasma triglycerides

Front 62

FH is a disorder of ....

Back 62

gene encoding the LDL receptor

Front 63

What accumulates in the plasma of FH patients?

Back 63

LDL

Front 64

Two types of depositions of LDL

Back 64

1)xanthomas (tendons and skin)
2)atheroma (arteries)

Front 65

inherritance pattern of FH

Back 65

autosomal dominant

Front 66

3 characteristics of atherosclerosis

Back 66

1)accumulation of cholesteryl esters in arterial wall fro macrophage foam cells (filled with chol. esters)
2) smooth muscle proliferation
3) fibrosis

Front 67

3 things that happen if your body senses enough cholesterol

Back 67

1) decrease HMG CoA Reductase
2) increase ACAT (storage)
3)decrease LDL receptors

Front 68

How does LDL bind to the LDL receptor?

Back 68

Apo B-100

Front 69

LDL receptor is what kind of protein?

Back 69

integral membrane protein

Front 70

where is the LDL receptor synthesized?

Back 70

on membrane-bound ribosomes in the ER

Front 71

How does the LDL receptor travel to the Golgi?

Back 71

vesicular transport

Front 72

What does the LDL receptor require?

Back 72

N-linked co-translational glycosylation

Front 73

Where does the LDL receptor travel from the Golgi?

Back 73

to the cell surface

Front 74

LDL receptor assocaites with __ at the cell surface?

Back 74

clathrin-coated pits

Front 75

purpose of endosomes

Back 75

acidified compartments- allows LDL to dissociate from the LDL receptor

Front 76

What happens in the lysosomes?

Back 76

proteins degraded to aa
cholesterol released

Front 77

What two things does SREBP regulate?

Back 77

HMG CoA Reductase
LDL Receptor Synthesis

Front 78

Which part of the SREB acts as a transcriptional activator?

Back 78

N-terminal domain

Front 79

When are SREBP activated to go into the nucleus and bind to SREs?

Back 79

at low cholesterol levels

Front 80

Two functions of the LDL receptor

Back 80

1) removes IDL (precursor of LDL)
2) takes up LDL directly

Front 81

What happens to LDL receptors when eat alot of sat fats and cholesterol?

Back 81

downregulate LDL receptors....increases plasma LDL levels

Front 82

Treatment for Heterozygote FH

Back 82

1)Bile acid binding resins
2) HMG CoA reductase inhibitors
3) diet

Front 83

Two examples of bile acid binding resins

Back 83

cholestryamine and colestipol

Front 84

How do bile acid binding resins work?

Back 84

bind bile acids in intestinal lumen and prevent absorption- increased fecal excretion of bile acids
-body converts more cholesterol to bile acids...liver responds to chol. deficiency by upregulationg production of LDL receptors

Front 85

How do statins work?

Back 85

1) inhibit HMG CoA reductase
2) also inhibit VLDL synthesis (precursor of LDL)-
* cell senses chol. decrease and increases LDL receptors and plasma clearance

Front 86

problem with using bile acid depletion alone?

Back 86

body not only up regulates LDL receptors, but also increases de novo synthesis of cholesterol- soln is to use in combo with statin

Front 87

treatment of homozygote FH

Back 87

1) plasma exchange- LDL apheresis- everything bound to Apo- B100 removed (not HDL)
2) liver transport
3) gene therapy