Duan > Lipowhatthefuckever Flashcards
1
Q
what are lipoproteins?
A
protein-lipid complexes responsible for transport of plasma lipids
2
Q
what is on the surface of a lipoprotein?
A
phospholipids (duh)
unesterified cholesterol
apolipoproteins
3
Q
what is in the core of a lipoprotein?
A
cholesterol esters
triglycerides
4
Q
what are the 3 lipids?
A
triacylglycerol
phospholipids
cholesterol & cholesterol esters
5
Q
what is the difference btwn triacylglycerol & phosopholipid?
A
triacylglycerol has 3 FAs w/ a glycerol backbone, phospholipids only have 2 FAs
6
Q
where is Apo A-I?
A
liver & small intestine
7
Q
what does Apo A-I do?
A
structural
activate LCAT
8
Q
where is Apo A-II?
A
liver
9
Q
what does Apo A-II do?
A
strucutral
inhibit hepatic lipase
component of ligand for HDL binding
10
Q
where is Apo A-IV?
A
small intestine
11
Q
what does Apo A-IV do?
A
activate LCAT
modulate LPL
12
Q
where is Apo A-V?
A
liver
13
Q
what does Apo A-V do?
A
direct fxnal role unk
regulates TG levels
14
Q
where is Apo B-100?
A
liver
15
Q
what does Apo B-100 do?
A
structural
synthesize VLDL
ligand for LDL-Receptor
16
Q
what does Apo B-48 do?
A
structural
make chylomicrons
17
Q
where is Apo B-48?
A
small intestine
18
Q
what is Apo B-48 from?
A
from apo B-100 mRNA after specific mRNA editing
19
Q
where is apo C-I?
A
liver
20
Q
what does apo c-I do?
A
activate LCAT
inhibit hepatic TGRL uptake
21
Q
what does apo C-II do?
A
activate LPL
inhibit hepatic TGRL uptake
22
Q
where is apo C-II?
A
liver
23
Q
where is apo C-III?
A
liver
24
Q
what does Apo C-III do?
A
inhibit LPL
inhibit hepatic TGRL uptake
25
where is apo E?
liver
macrophages
brain
26
what does apo E do?
ligand for apoE receptor
| mobilize cellular cholesterol
27
which lipoproteins are in the liver?
```
A-I
A-II
A-V
B-100
C-I
C-II
C-III
E
```
28
which lipoproteins are in the small intestine?
A-I
A-IV
B-48
29
which lipoproteins are in macrophages & the brain?
ONLY E!
30
what is the smallest lipoprotein?
HDL
31
how big is HDL?
9-15 nm
32
how big is LDL?
20-22 nm
33
how big are chylomicrons, VLDL, and their catabolic remnants?
>30 nm
34
what are the biggest lipoproteins?
chylomicrons, VLDL, and their catabolic remnants
35
what is the density of HDL?
1.063-1.21 g/mL
36
what is the density of LDL?
1.019-1.063 g/mL
37
what is the density of chylomicrons, VLDL, & their catabolic remnants?
<1.006 g/mL
38
what affects the diameter & density of lipoproteins?
CE/TG/phospholipid/lipoprotein composition
39
what is the % total lipid & % total protein content of HDL?
50%
| 50%
40
what is the % total lipid & % total protein content of LDL?
80% total lipid
| 20% total protein
41
what is the % total lipid & % total protein content of IDL?
85% total lipid
| 15% total protein
42
what is the % total lipid & % total protein content of VLDL?
92% total lipid
| 8% total protein
43
what is the % total lipid & % total protein content of chylomicrons?
99% total lipid
| 1% total protein
44
what 3 things make up total lipid content?
CE
TG
phospholipids
45
what is the general trend as density of a particle decreases with total lipid and total protein?
lower density = larger diameter
higher lipid content
lower protein content
46
what are the 2 pathways for lipoprotein metabolism?
exogenous/chylomicron pathway
| endogenous/VLDL pathway
47
what pathway does dietary fat use for lipoprotein metabolism?
exogenous/chylomicron
48
what happens to lipids synthesized by the liver (what lipoprotein metabolism pathway)?
endogenous/VLDL pathway
49
what are the 5 steps of the exogenous/chylomicrons pathway?
1. bile salts solubilize dietary TG
2. pancreatic lipases hydrolyze TGs
3. diffuse into intestinal epithelial cells
4. ER re-synthesizes TG
5. packaged into chylomicrons
50
what is the half life of a chylomicron?
5-30 min
51
which apolipoproteins are in chylomicrons initially?
apo A
| apo B-48
52
which apolipoproteins on chylomicrons are acquired in circulation?
apo E
| apo Cs
53
what activates LPL?
apo C-II
54
where is LPL primarily?
on surface of capillaries of adipose & muscle tissue
55
what does LPL do?
hydrolyze TG to free FA + glycerol
56
what % of a chylomicron is TG?
>90%
57
what % of a chylomicron is CE + cholesterol?
<5%
58
what % of a chylomicron is phospholipids?
5-10%
59
what % of a chylomicron is protein?
1-2%
60
what happens to the free FA from a chylomicron?
can be reused for energy or re-esterified
61
what happens to chylomicrons as they lose TG?
they shrink
62
what do apo E and apo C get transferred to (from a chylomicron)?
HDL
63
what is a chylomicron called when all the apo C is gone?
chylomicron remnants
64
what is the composition of a chylomicron remnant?
CE > TG
65
what happens to LPL after the chylomicron loses apo C-II?
no longer activated
66
what happens to chylomicron remnants?
taken up by liver
67
what is the half-life of a chylomicron remnant?
~5 min
68
what is the function of a chylomicron?
transport dietary lipids from the intestines to adipose, skeletal, & cardiac muscle tissue
69
where does a chylomicron get apo C II and apo E?
from HDL
70
what apolipoproteins does a chylomicron remnant have?
apo E
| apo B-48
71
what is VLDL responsible for?
endogenous TG formation & transport
72
are VLDLs bigger or smaller than chylomicrons?
smaller
73
what is the surface monolayer of VLDL composed of?
12% phospholipids
14% free cholesterol
4% protein
74
what is the hydrophobic core of VLDL composed of?
65% TG
8% CE
C 8-10%, CE 12-15%
idk man this is weird
75
what lipoproteins does VLDL have?
apo Cs (C-II from HDL)
apo E
apo B-100
76
what is the half-life of VLDL?
~12 hours
77
what are TGs hydrolyzed by?
LPL
78
VLDLs decrease in size to become what?
IDL
79
what happens if you lose Apo C-II?
less activation of LPL
80
what is the composition of IDL?
TG about the same as CE
81
what lipoproteins are on IDL?
apo Cs
Apo E
Apo B-100
82
what is the half-life of IDL?
minutes to an hour
83
what takes up 50% of IDLs?
the liver
| via apoE & Apo B-100
84
what happens to the IDLs that do not get taken up by the liver?
loses TG
| becomes LDL
85
what is the primary carrier of cholesterol in the blood?
LDL
86
what lipoprotein has the highest cholesterol?
LDL
87
what is the composition of LDL?
5% TG
20% protein
70% C + CE
88
what removes LDL?
LDLR via apo B-100
89
what is the half life of LDL?
2.5-3 days
90
what lipoproteins have apo B-100?
VLDL, IDL, LDL
91
increased apo B-100 is correlated w/ what?
increased CVS disease
92
what is the genetic defect assoc w/ familial defective apo B?
glutamine substituted arginine at amino acid 3500 > missense mutation
93
what is familial defective apo B?
affects binding affinity of apo B-100 at its receptor (i.e. the LDL receptor)
94
where can you find the LDL receptor?
hepatic & extrahepatic tissues
95
what happens when an LDL particle binds to the receptor?
the receptor-LDL complex is endocytosed
96
what happens to the cholesterol in LDL after the LDL-receptor complex is endocytosed?
cholesterol is de-esterified & released as free cholesterol in cytoplasm > can be used in membranes
97
what re-esterifies XS cholesterol?
ACAT
| acyl-CoA-cholesterol acyl transferase
98
what pathway occurs in the small intestine?
exogenous pathway
99
what pathway occurs in the liver?
endogenous pathway
100
what does ACAT do in the intestine/exogenous pathway?
regulates dietary cholesterol absorption
101
what does ACAT do in the liver/endogenous pathway?
esterifies cholesterol for production & release of VLDL
102
what does ACAT promote?
foam cell formation & atherogenesis
103
what does LDL come from?
VLDL
| + LPL
104
where is HDL synthesized?
liver & small intestine
105
what does HDL do?
transports cholesterol from peripheral tissues to liver
106
what is the composition of HDL?
CE & phospholipids (50/50)
107
what lipoproteins are present in HDL?
apo A-I
apo A-II
apo C-II
apo E
108
what is the cofactor for LCAT?
apo A-I
109
what is LCAT?
lecithin cholesterol acyl trasnferase
110
what does LCAT do?
esterifies cholesterol > moves into interior of particle to enlarge HDL
111
what happens to HDL particles as the circulate through the bloodstream?
they acquire cholesterol & phospholipids and grow
112
what does CETP do?
exchange VLDL TGs against HDL CEs
113
what are the 2 mechanisms of cholesterol regulation?
1. rate of cholesterol synthesis
| 2. rate of LDL receptor transcription
114
what are the 4 primary lipoprotein disorders?
primary chylomicronemia
familial hypertriglyceridemia
familial combined hyperlipoproteinemia
familial dysbetalipoproteinemia
115
what is primary chylomicronemia?
LPL or cofactor deficiency
| increased chylomicrons & VLDL
116
what is the result of hypertriglyceridemia?
increased VLDL
| +/- chylomicrons
117
what is the result of familial combined hyperlipoproteinemia?
```
increased VLDL
OR
increased LDL
OR
both
```
118
what is the result of familial dysbetalipoproteinemia?
increased VLDL remnants & chylomicron remnants
119
what do mutations in the LDL receptor lead to?
familial hypercholesterolemia
120
what do most LDL receptor mutations result in?
impaired fxn
121
what do SOME LDL receptor mutations result in?
fewer receptors d/t impaired cell processing
122
what is the clinical result of heterozygous LDL receptor mutation?
serum cholesterol up to 2x normal
| ~5% have MI before 60yo
123
what is the clinical result of homozygous LDL receptor mutaiton?
high serum cholesterol
CVD signs at an early age
MI by 20yo
124
are hetero or homozygous mutations in the LDL receptor more common?
heterozygous (1 in 500)
| homo is 1 in 1 million
125
what happens to TGs in alcoholism?
increase
126
what happens to TGs in liver disease?
increase
127
what happens to VLDL & chylomicrons in alcoholism & liver disease?
VLDL is low to normal
| chylomicrons increase
128
T/F: only type 1 diabetes increases risk for CVD
FALSE
| type 1 & 2
129
how does insulin affect LPL transcription?
increases it
increased removal of TGs
decreased VLDL
130
what happens to LPL transcription if insulin is low or if pt is insulin resistant?
decrease in LPL transcription
131
what happens to VLDL if insulin is low or if pt is insulin resistant?
increase VLDL
| less effect of chylomicrons
132
what happens to proteins & lipids with high blood sugar?
can become glycated
| increased risk of atherogenesis
133
what are the LDL mods in atherosclerosis?
oxidation of apo B-100
| glycation
134
HDL has at least 2 antioxidant enzymes that can inhibit or reverse WHAT?
oxidation
135
what is a scavenger receptor?
binds to modified LDL (in atherosclerosis) & endocytosed the particles
136
what are foam cells?
cholesterol accumulates in macrophages > XS is deposited as droplets in cytoplasm
137
how does LDL impact atherosclerosis?
LDL moves out of arterial lumen & into arterial wall > modified & oxidized > inflammation > foam cells
138
what is the first step for therapy for atherogenic heart disease?
lowering plasma LDL thru diet & meds
139
how do statins work (GENERALLY)?
block cholesterol production
| increase expression of LDL receptor by liver
140
what is another name for the statins?
HMG-CoA reductase inhibitors
141
what are the 6 statins you need to know?
```
lovastatin
simvastatin
pravastatin
fluvastatin
atorvastatin
rosuvastatin
```
142
what are the 4 mechanisms of action of the statins?
inhibits HMG-CoA reductase
decrease in cholesterol synthesis
increased synthesis of hepatic LDL receptors
increased LDL uptake
143
how do statins impact TG, LDL, & HDL?
= or dec TG
dec LDL
= or inc HDL
144
what are the clinical uses of statins?
lowering LDL
heterozygous familial hypercholesterolemia
secondary hypercholesterolemia d/t diabetes
145
what can you combine statins w/ to achieve greater effects & 50% reduction in LDL?
bile acid-binding resins
or
ezetimibe
146
when does the majority of cholesterol synthesis occur?
at NIGHT
147
when are statins most effective (what time of day)?
at NIGHT bc that's when cholesterol synthesis occurs
148
what are 2 other possible uses for statins?
osteoporosis
| anti-inflammatory (modulate immune system AND decrease high sensitivity CRP)
149
what are the side effects of statins?
HA
photosensitivity
MYALGIA & MYOPATHY (grapefruit!)
rarely liver damage
150
how are statins cleared?
P450A (CYP3A4)
151
what can statins interact w/?
```
GRAPEFRUIT JUICE
dihydropyridine CCBs
St. John's wort
fibrates
niacin
ketoconazole
erythromycin
```
152
what is a possible consequence of statin therapy w/ other drugs?
increase levels of oral contraceptives, digoxin, & warfarin
153
what are the bile acid-binding resins?
cholestyramine
colestipol
colesevelam
154
what is the mechanism of action of bile acid binding resins?
anion exchange resin
| binds bile acids in intestine > increased fecal excretion of bile acid
155
how do bile acid binding resins get absorbed?
they DON'T!
| they're hydrophobic & unaffected by digestive enzymes so they remain unchanged
156
what are the results of bile acid binding resins?
increased pdtion of LDL receptors
| increased activity of HMG-CoA reductase
157
how are TGs, LDL, and HDL affected by bile acid binding resins?
inc or dec TGs
decreased LDL
= HDL
158
when do you use bile acid binding resins?
pts w/ high LDL
159
what do bile acid binding resins have an ADDITIVE effect in lowering LDL w/?
nicotinic acid & statins
160
what are the side effects of bile acid binding resins?
GI probs, nausea, indigestion
steatorrhea in high dose
impaired absorption of vitamins (A, D, E, K, folic acid)
may cause hyperchloremic acidosis
