Exam 3 - Lipoproteins Flashcards
1
Q
Ideal healthy level of total cholesterol
A
<200 mg/dl
2
Q
Ideal healthy level of LDL - cholesterol
A
<100 mg/dl
3
Q
Ideal healthy level of HDL - cholesterol
A
> 60 mg/dl
4
Q
Ideal healthy level of triglycerides
A
<150 mg/dl
5
Q
Most abundant lipids in the body
A
- triglycerides
- phospholipids
- cholesterol
6
Q
Which lipid is a major source of energy for cells?
A
Triglycerides
7
Q
Major lipid component of cell membranes
A
Phospholipids
8
Q
Majority of cholesterol is made in the:
A
Liver
9
Q
Function of cholesterol
A
- cell growth
- cell division
- membrane repair
- steroid/hormone production
- bile salts
10
Q
Triglycerides structure
A
3 fatty acids to glycerol via ester linkage
high density energy store
11
Q
Phospholipids structure
A
2 fatty acids linked to glycerol backbone, with phosphate/polar head group
12
Q
Cholesterol is made into a cholesterol ester via what enzyme?
A
LCAT (lecithin cholesterol acyltransferase)
13
Q
Cholesterol from the diet is only found in:
A
Animal fat
14
Q
Cholesterol biosynthesis occurs primarily in the liver using:
A
Acetyl-CoA
15
Q
Degradation of cholesterol only occurs in the:
A
Liver
16
Q
What forms of metabolic fuel are found in the blood?
A
- glucose
- fatty acids
17
Q
After eating, glucose becomes ____ and excess gets converted into ____
A
oxidized; glycogen
18
Q
What form of fuel is used during fasting?
A
Fatty acids
19
Q
Metabolic fuels are used ____
A
Inversely
20
Q
____% of fatty acid is present as free fatty acid form (unesterified)
A
2-5% (95% in the form of fatty acid esters)
21
Q
Free fatty acids are derived from:
A
- intracellular hydrolysis of triglycerides in hepatic or adipose cells
- lipoprotein lipase acting on circulating lipoproteins
22
Q
During a fed state, insulin inhibits ______ and stimulates ____ and ____
A
hormone-sensitive lipase; triglyceride synthesis and LPL
23
Q
Insulin during fed state results in:
A
Storage of triglycerides (don’t need to use fatty acids as fuel if glucose is present)
24
Q
During fasting, there is a drop in ____ which activates _____ (enzyme). ____ are hydrolyzed in adipocytes
A
Insulin; hormone sensitive lipase; Triglycerides
25
Hormone sensitive lipase function
Make fatty acids available to cells/tissues that need it (in presence of insulin)
26
Function of lipoprotein lipase
Removes fatty acids off of lipoproteins so they can be mobilized/stored in the fat cell
27
True or false: lipids can be transported without aid in the bloodstream
False - they are insoluble so they need to be associated with lipoproteins for transport
28
Lipoprotein structure
- spherical soluble particle
- nonpolar lipids in core (TG and cholesterol esters)
- polar aspects toward aqueous phase
29
Where are apoproteins located with respect to the lipoprotein?
On the outside (outermost) in aqueous phase
30
What are apoproteins?
Proteins associated with lipoproteins
31
Functions of apoproteins
- structural role
- binding sites for receptors
- activators or co-enzymes for lipid metabolism
32
____ direct the fate of lipoproteins
Apoproteins
33
What are the different classifications of lipoproteins?
- Chylomicrons
- VLDL
- IDL
- LDL
- HDL
34
Which lipoprotein has the highest density? Why?
HDL - lowest amount of triglycerides and smallest
35
Largest lipoprotein
Chylomicron (also least dense)
36
Density of lipoproteins is based on:
Buoyant density compared to physiological saline
37
Larger lipoprotein particles means that there is:
- higher content of triglycerides
- lower density
38
Smaller lipoprotein particles means there is:
- less triglycerides
- greater relative mass of protein
- enriched in cholesterol esters
- greater density
39
Lipoproteins on gel electrophoresis - what is significant about chylomicrons?
Trapped at origin (much larger in size so they get stuck)
40
Apoproteins can be exchanged between different lipoproteins except for:
Apo B100 and Apo B48
41
True or false: Apo B100 and Apo B48 can exist on the same lipoprotein particle
False - only one or the other
42
Between different lipoproteins, protein content can vary such as:
Number and types of proteins associated with them
43
Besides proteins, what else can be exchanged between lipoproteins?
- Surface phospholipids and cholesterol
- cholesterol esters and TGs (but needs cholesterol ester transfer protein)
44
Source of chylomicrons
Gut/intestine
45
Chylomicrons - apoproteins associated
- B48
- CII
- E
46
Function of chylomicrons
- transport dietary triglycerides
- FFA goes to adipose/muscle
- cholesterol esters goes to liver as remnants
47
Source of VLDL
Liver
48
VLDL - apoproteins associated
- B100
- CII
- E
49
VLDL function
- transports endogenous triglycerides
- FFA goes to adipose/muscle
- cholesterol esters go to LDL
50
Source of LDL
Blood (remnant of VLDL)
51
LDL apoproteins associated
B100
52
LDL function
- transports cholesterol (from VLDL) to peripheral tissues
- cholesterol esters go to liver and peripheral cells
53
Source of HDL
Liver
54
HDL - apoproteins associated
- A1
- CII
- E
55
HDL function
- reverse cholesterol transport
- removes used cholesterol from tissues and brings to liver
- donates apolipoproteins to CM and VLDL
56
Apoprotein A1 site of action
Blood, plasma membrane
57
Function of apoprotein A1
- activates LCAT and CETP
- binds to apo A1 receptors on cells that require cholesterol extraction (HDL)
58
Apoprotein B48 site of action
Gut (chylomicrons)
59
Apoprotein B48 function
- structural
- export of chylomicrons from intestinal cells (enterocytes)
60
Apoprotein B100 site of action
Various cells (VLDL and LDL)
61
Apoprotein B100 function
- structural
- ligand for LDL receptor
- export of liver VLDL
62
Apoprotein CII site of action
Capillary walls
63
Apoprotein CII function
Activates lipoprotein lipase (LPL)
64
Apoprotein E site of action
Liver
65
Apoprotein function
Receptor ligand - clears remnants, IDL, and HDL
66
ApoB100 and ApoB48 are from the same gene - which one is larger?
ApoB100 (it is the entire gene, ApoB48 is 48% the size of B100)
67
Which apoprotein is produced exclusively by the intestine?
ApoB48
68
ApoB48 formation is a result of:
- Tissue-specific expression of editase, a cytidine deaminase
- changes cytidine into uracil, glutamine codon CAG becomes UAG stop codon at position 6666
| mRNA-editing enzyme activity
69
____ are absent in a fasting state
Chylomicrons
| once you consume the dietary fats you ingested, they are gone
70
Chylomicrons are assembled in:
Intestinal mucosal cells
71
How do chylomicrons form and enter the bloodstream?
- hydrolysis of triglycerides into fatty acids
- Fatty acids cross cell membrane of enterocytes
- fatty acids are reassembled into TGs inside the intestinal cell and packaged into chylomicron
- Chylomicron enters lacteal
- Enters lymphatic system
- then enters blood via thoracic duct
72
As chylomicrons circulate in the blood, they acquire apoproteins:
A, CII and E
73
Triglyceride content of chylomicrons
86%
74
True or false: chylomicrons can vary in size
True - size of particles depends on the amount of triglyceride available (based on dietary intake)
75
Triglyceride composition of chylomicron closely resembles:
Dietary intake
76
VLDL triglyceride content
55% (also contains significant amount of cholesterol and CE)
77
Nascent VLDL contains which apoprotein?
B100 (major structural apoprotein)
78
___ acts upon VLDL in order to liberate FFA
LPL
79
Lipolysis created _____ VLDL remnants
smaller, more cholesterol ester-rich
80
VLDL assembly occurs in what kind of cells?
Hepatocytes (through uptake of recycled plasma lipoproteins)
81
Three sources of fatty acids for VLDL assembly
- plasma FFA that dissociate from albumin
- from TG-rich lipoproteins that have undergone receptor-mediated endocytosis
- synthesis in liver de novo
82
VLDL secretory particles are released into:
the space of Disse
83
50% of VLDL is lipolytically converted into:
IDL and LDL
84
IDL is enriched in:
Cholesterol esters
85
LDL is ____-rich
Cholesterol
86
95% of protein in LDL is:
ApoB100
87
LDL contributes to ____ of the cholesterol found in plasma
70
88
Best single predictor of increased risk of atherosclerosis
High level of plasma LDL or apoB100
89
Lipoprotein lipase - site of action and activator
Site of action: capillary walls
Activator: Apo CII
90
ACAT (acyl-CoA cholesterol acyltransferase) - site of action and activator
Site of action: inside cells
Activator: free choles
91
ACAT function
cholesterol ester storage
92
LCAT (lectin cholesterol acyltransferase) site of action and activator
Site of action: blood
Activator: Apo A1
93
LCAT function
Cholesterol extraction from cells (HDL carries CE for liver clearance to bile acids)
94
CETP - site of action and activator
Site of action: plasma membrane
Activator: apo A1 (choles included)
95
CETP function
flips cholesterol and lecithin to outer layer of lipid bilayer for LCAT action in blood
96
Apo CII activates lipoprotein lipase which breaks down _____ into ____ and _____
Triglycerides; free fatty acids and glycerol backbone
FFA goes to muscle and adipose, glycerol goes to liver
97
LPL is attached to inner wall of capillary via:
Polysaccharide chain
98
Review endogenous and exogenous pathways on slides
99
When HDL goes back to the liver it is:
Degraded
100
Cholesterol is excreted as ____ or ____ from HDL
bile salts; repackaged in VLDL
101
Cholesterol synthesis in the liver is regulated by:
Cholesterol arriving through HDL
102
Lipoprotein clearance involves irreversible removal from ____
Plasma
103
Chylomicrons half life
1 hour - cleared by liver E receptor
104
Large VLDL half life
Minutes; 50% cleared by liver, 50% to IDL/LDL
105
Small VLDL/IDL half life
1-2 hours, converted to LDL
106
LDL half life
2-3 days
107
Why does LDL have a longer half life?
Loss of ApoE -- loss of Apo E receptors on the liver so takes longer to clear but longer access to extrahepatic tissues
108
____% of plasma LDL is cleared by the liver
40%
109
____ of plasma LDL is cleared by extrahepatic tissues
60%
110
_____ is preferentially used by extrahepatic tissues as opposed to de novo cholesterol synthesis
LDL cholesterol
111
70% of LDL clearance is mediated by ____; remainder is by _____
LDL receptors; scavenger receptors (macrophages)
112
LDL cholesterol is taken up into cells via ____
clathrin coated pits (endocytosis)
113
Increased cholesterol causes inhibition of:
- inhibits production of cholesterol
- inhibits LDL receptor synthesis (less HMGCoA reductase, so less synthesis of endogenous receptors)
114
Mutations in LDL receptors causes increased ____ and therefore _____
plasma LDL levels; accelerates progress of atherosclerosis
115
What is the function of HMGCoA reductase?
responsible for synthesizing cholesterol
116
Statin drugs decrease ____ by targeting ____
LDL; HMGCoA reductase
117
Type 1 Hyperlipoproteinemia: defect, lipoprotein in excess, lipid elevations
- defect: Decreased LPL or altered ApoCII
- lipoprotein in excess: chylomicrons
- lipid elevations: triglycerides
118
Type 2 Hyperlipoproteinemia: defect, lipoprotein in excess, lipid elevations
- defect: LDL receptor deficiency
- lipoprotein in excess: LDL
- lipid elevations: cholesterol
119
Type 2b Hyperlipoproteinemia: defect, lipoprotein in excess, lipid elevations
- defect: decreased LDL receptor, increased ApoB
- lipoprotein in excess: LDL and VLDL
- lipid elevations: cholesterol and triglyceridea
120
Type 3 Hyperlipoproteinemia: defect, lipoprotein in excess, lipid elevations
- defect: defective ApoE synthesis
- excess: VLDL and IDL
- lipid elevations: cholesterol and triglycerides
121
Type 4 Hyperlipoproteinemia: defect, lipoprotein in excess, lipid elevations
- defect: increased VLDL synthesis
- excess: VLDL
- elevated: triglycerides
122
Type 5 Hyperlipoproteinemia: defect, lipoprotein in excess, lipid elevations
- defect: increased VLDL production, decreased LPL
- excess: VLDL and chylomicrons
- elevated: cholesterol and triglycerides
123
Corneal arcus is associated with hyperlipoproteinemia types ____ in what population?
2 and 3; males over 40
124
Corneal arcus is predictive of:
increased risk of coronary artery disease
125
Corneal arcus looks like:
Ring around cornea
126
Tendon xanthoma is found in:
Type 2a hyperlipoproteinemia
127
Increased LDL circulation can be acted on by _____ and taken up by _____. These then become ____ cells which can deposit into artery walls and cause _____ to develop
Oxygen radicals; scavenger receptors on macrophages; foam cells; atherosclerosis/CAD
128
Common cause of accelerated atherosclerosis is:
Deficiency of LDL receptors
can also be inherited defect or high cholesterol/high saturated fat diet
129
Foam cells are ____ filled with ____
Macrophages; cholesterol esters
130
Oxidized LDL stimulates endothelial cells to release _____ to recruit ____ to the arterial wall
cytokines; monocytes
131
Foam cells form a ____ as part of the atherogenic plaque
Fatty streak
132
Elevated LDL means that there is increase in:
- residence time in plasma
- modification and oxidation of LDL
