Flipped Classroom: Lipoproteins III Flashcards
(100 cards)
1
Q
The second receptor-mediated fate for circulating LDL is via the
A
Scavenger receptor
2
Q
Has a lower affinity but broader specificity than the LDL receptor
A
Scavenger receptor
3
Q
The scavenger receptor can recognize both
A
Normal and damaged LDL
4
Q
Macrophages and some endothelial cell types possess the
A
Macrophage scavenger receptor (SR-A)
5
Q
Significant percentages of LDL uptake in organs such as the intestine and spleen are accounted for by the
A
Scavenger receptor
6
Q
SR-A has a higher affinity for
A
Oxidized (damaged) LDL
7
Q
Leads to foam cell formation
A
SR-A
8
Q
Even after mRNA has been fully processed, it may undergo additional posttranscriptional modification in which a base in the mRNA is altered. This is known as
A
RNA editing
9
Q
The apoB mRNA is made in the
A
Liver and small intestine
10
Q
However, in the small intestine only, the C residure in the codon CAA for glutamine is deaminated to U, changing this to a
A
Stop codon
11
Q
This results in translation of the shorter protein known as
A
ApoB-48
12
Q
What makes
- ) ApoB-100
- ) ApoB-48
A
- ) Liver (incorporated into VLDL)
2. ) Intestines (Chylomicron)
13
Q
A circulating, abnormal varient of LDL
A
Lipoprotein(a) aka Lp(a)
14
Q
Forms when ApoA forms a disulfide bonded complex with the ApoB-100 component of LDL
A
Lp(a)
15
Q
A modest independent risk factor for atherosclerotic cardiovascular disease events, especially an MI
A
Lp(a)
16
Q
Certain SNPs of the LPA gene maybe be associated with higher population risks for
A
CVD
17
Q
VLDLs travel in the circulatory system until they associate with LPL. This association is mediated via
A
ApoC-II
18
Q
Serves to remove excess cholesterol from the peripheral tissues and return it to the liver
A
Reverse cholesterol pathway
19
Q
This movement is accomplished by
A
HDL
20
Q
Transport of cholesterol from the liver to peripheral tissues is called
A
Cholesterol transport
21
Q
While the transport of cholesterol from the peripheral tissues to the liver and steroid producing tissues is called
A
Reverse cholesterol transport
22
Q
Formed in the blood by the addition of ipid to ApoA-I
A
HDL
23
Q
Accounts for about 70% of the apoproteins in HDL
A
ApoA-I
24
Q
Serves as a circulating reservoir of ApoC-II and ApoE
A
HDL
25
The apolipoprotein that is transferred to VLDL and chylomicrons and is an activator of LPL
ApoC-II
26
The apolipoprotein required for the receptor-mediated endocytosis of IDLs and chylomicron remnants
ApoE
27
Nascent HDL particles are derived from both the
Liver and intestine
28
Unlike the chylomicron and VLDL, the nascent HDL is not spherical but rather
Disc-shaped
29
Are also derived from surface components of both chylomicrons and VLDLs
HDL particles
30
ApoA-I activates
LCAT
31
ApoA-II activates
HL
32
Protein that is secreted by the liver and circulates in plasma, bound mainly to HDL
Cholesterol Ester Transfer Protein (CETP)
33
Promotes the redistribution of cholesterol esters, triglycerides, and, to a lesser extent, phospholipids netween plasma lipoproteins
CETP
34
The overall net effect of CETP is a net mass transfer of cholesterol esters from HDL to triglyceride-rich lipoproteins and
LDL
35
Also has the net effect of moving triglycerides from triglyceride-rich lipoproteins to LDL and HDL
CETP
36
Subsequently, the TAGs are removed from HDL by
HL
37
One consequence of these CETP-mediated transfers of cholesterol esters from HDL is a reduction in the cholesterol content and size of
HDL
38
The overall effect of CETP is a net mass transfer of cholesterol esters from HDL to
VLDL
39
The overall effect of CETP is also a net mass transfer of triglycerides from VLDL to
HDL
40
Nascent HDL form chiefly in the liver and intestine by loading phosphatidylcholine, cholesterol, and cholesterol esters onto
ApoA-I
41
Used by the liver to enrich discoidal HDL w/ phosphatidylcholine and cholesterol
ABCA1 transporter
42
When colesterol is taken up by HDL, it is immediately esterified by the plasma enzyme
LCAT
43
LCAT is synthesized and secreted by the
Liver
44
LCAT binds to nascent HDL and is activated by
ApoA-I
45
Transfers the fatty acid from carbon 2 of phosphatidylcholine to cholesterol, producing a hydrophobic cholesterol ester
LCAT
46
Whic HDL is more cholesterol ester rich, HDL3 or HDL2?
HDL2
47
CETP moves some of the cholesterol esters from HDL to VLDL in exchange for TAG, relieving product inhibition of
LCAT
48
Because VLDLs are catabolized to LDL, the cholesterol esters transferred by CETP are ultimately taken up by the
Liver
49
The uptake of cholesterol esters by thge liver is mediated by a cell-surface receptor
-Binds HDL
SR-B1
50
The HDL particle itself is not taken up. Rather, there is selective uptake of the cholesterol ester from the
HDL particle
51
With it's ability to degrade both TAG and phospholipids, participates in the conversion of HDL2 to HDL3
HL
52
Elevation of plasma cholesterol, triglycerides (TGs), or both, or a low HDL level that contributes to atherosclerosis
Dyslipidemia
53
Can result from a single inherited gene defect, or more commonly, are caused by a combination of genetic and environmental factors
Primary hyperlipidemias
54
The result of a metabolic disorder such as DM, obesity, hypothyroidism, or primary biliary cirrhosis
Secondary hyperlipidemias
55
How do we calculate LDL cholesterol?
-the Friedewald equation (mg/dL)
LDL cholesterol = Total cholesterol - HDL - VLDL
56
The Friedewald equation is inaccurate when the concentration of triglycerides is high (greater than 400) or when there is an appreciable number of
Chylomicrons
57
How do we calculate VLDL cholesterol?
Total triglycerides/5
58
Patients who have hypertriglyceridemia mayhave normal or elevated
LDL cholesterol
59
Hypertriglyceridemia is defined as total plasma triglycerides in the fasting state in excess of
150 mg/dL
60
The hyertriglyceridemia is due to an abnormally high quantity of
Chylomicrons, VLDL, or both
61
The major risk of very severe hypertriglyceridemia is
Pancreatitis
62
Patients who hace very severe hypertriglyceridemia may also have
Eruptive and tuberous xanthomas
63
Characterized by the pathologic presence of chylomicrons after a 12-14 hour period of fasting
Familial chylomicronemia
64
In familial chylomicronemia, samples of lipemic plasma that are refridgerated overnight develop a
Creamy supernatant
65
When the plasma is tested, fasting triglyceride measurements are typically above
1000 mg/dL
66
Lowering of plasma triglycerides to below 500 mg/dL virtually eliminates a person's risk of a repeat episode of hypertriglyceridemia-induced
Pancreatitis
67
Due to deficiency of LPL and ApoC-II activity
Familial chylomicronemia
68
Has secondary factors and a greater elevation of total cholesterol relative to that in familial chylomicronemia
Primary mixed hyperlipidemia
69
Characterized by the accumulation of remnants of chylomicrons and of VLDLs
Dysbetalipoproteinaemia
70
This is because Dysbetalipoproteinaemia develops due to a deficiency of
ApoE
71
Has a population prevalence of 1-2 in 20,000
Familial dysbetalipoproteinaemia
72
Plasma levels of LDL levels are decreased and plasma levels of IDL are increased because of interrupted processing of VLDL in
Dysbetalipoproteinaemia
73
An increased VLDL:triglyceride ratio and an ApoE homozygosity are therefore diagnostic for
Familial Dysbetalipoproteinaemia
74
The onset of Familial Dysbetalipoproteinaemia occurs after
Childhood
75
In women, onset of Familial Dysbetalipoproteinaemia is typically delayed until
Menopause
76
Clinical manifestations may very from no physical signs to severe cutaneous and tendinous xanthomata, atherosclerosis of coronary and peripheral arteries, and pancreatitis when severe hypertriglyceridemia is present
Familial Dysbetalipoproteinaemia
77
The cornerstone of treatment for hypertriglyceridemia
Lifestyle modification
78
Reduces VLDL production in a high dose
Statin
79
Increases LPL activity
Sipplement of fish oil rich in omega-3 FA
80
Activate PPARa transcription factors that lead to both increased lipoprotein lipase activity and an increased rate of fatty acid B-oxidation
Fibrate drugs
81
Works in part by activating niacin receptor 1 that inhibits lipolysis
Nicotinic acid (Vitamin B3)
82
People with hypercholesterolemia have a high risk of developing
Coronary artery disease
83
People that have two alleles for a defective LDL receptor have
Homozygous familial hypercholesterolemia
84
Have an LDL concentration that is 10x the normal concentration
Patients with Homozygous familial hypercholesterolemia
85
In less frequent circumstances, a patient can have Homozygous familial hypercholesterolemia due to two loss-of-function mutations in
ApoB-100
86
About 5% of heterozygous familial hypercholesterolemia pateints have a mutant
ApoB-100
87
About 2% of heterozygous familial hypercholesterolemia pateints have overactive
PCSK9 enzyme
88
Most patients who have heterozygous familial hypercholesterolemia have a mutant allele for the
LDL receptor
89
Patients with heterozygous familial hypercholesterolemia typically have how much more LDL than usual?
2x
90
Patients with heterozygous familial hypercholesterolemia that is untreated typically have heart attacks before their
Late 50's
91
Patients with Homozygous familial hypercholesterolemia typically have heart attacks in their
Teens and twenties
92
The most common lipoprotein abnormality among pateints with CAD
Low HDL (less than 40 mg/dL)
93
Low HDL is also a component trait of the
Metabolic syndrome
94
The most common genetic disorder of HDL is
Familial hypoalphalipoproteinemia (FHA)
95
Common finding in patients with premature CAD
FHA
96
Results in a profound decrease in HDL (less than 5 mg/dL)
Complete loss of ApoA-1
97
ApoA-1 deficient patients can be distinguished from other causes of HDL deficiency by the complete absence of
ApoA-1
98
Patients with ApoA-1 deficiency also have normal levels of
LDL and TAGs
99
Patients with HDL deficiency due to ApoA-1 deficiency may also exhibit mild to moderate
Corneal opacification or corneal clouding
100
Another cause of low HDL is
LCAT deficiency
