LIPIDS PART 2 Flashcards
1
Q
Carriers of lipids as they are insoluble in water. They
need to be carried by soluble molecules (protein).
A
lipoproteins
2
Q
Spherical with 10 nm to > 1um
A
lipoproteins
3
Q
are found on the surface of
lipoproteins
A
amphipathic lipids
4
Q
head group of
phospholipids, and apolipoproteins
A
free cholesterol
5
Q
Hydrophobic and neutral lipids are located in the core of lipoproteins
A
micelles
6
Q
Primary function: To transport the lipid-energy source
to peripheral cells
A
lipoproteins
7
Q
Outside is the soluble protein which is on the surface called
A
apolipoprotein
8
Q
High lipid content = larger core region = lighter
density
A
TRUE
9
Q
lowest density, highest lipid
content, largest core
A
chylomicrons
10
Q
The size of the lipoprotein particle correlates with its
______ content
A
lipid
11
Q
The larger lipoprotein particles have correspondingly
larger core regions and contain relatively more
triglyceride and cholesteryl ester
A
LARGER ;MORE
12
Q
The higher the protein content, the higher in density
A
TRUE
13
Q
CHON (protein) components of lipoproteins
● Maintains structural integrity
● Ligands for cell receptors
● Activators and inhibitors of enzymes
A
APOLIPOPROTEINS
14
Q
is the only one without Apolipoprotein B or ApoB
A
HDL
15
Q
formation requires ApoB-48
A
chylomicron
16
Q
structural LCAT activator ABCA1 lipid acceptor
A
APO A1
17
Q
major lipoprotein location: HDL
A
apo a1
apo a2
apo a4
18
Q
structural, LDL receptor ligand
A
apo b100
19
Q
located in chylos for structural, remnant receptor ligand
A
apo b 48
20
Q
located in chylos, VLDL, HDL for structural and LPL cofactor
A
apo c2
21
Q
located in chylos, VLDL, HDL but for structural only
A
apo c1
22
Q
located in chylos, VLDL, HDL for stuctural, LPL inhibitor
A
apo c3
23
Q
structural, plasminogen inhibitor located in Lp(a)
A
apo (a)
24
Q
for HDL
A
APO A
25
LDL/VLDL
APO B100
26
chylomicrons
APO B 48
27
Lipoproteins with Apo-B
chylomicrons
VLDL
LDL
28
Reverse cholesterol pathway:
HDL
29
carrier of exogenous lipids.
chylomicrons
30
Endogenous Production of Lipids happens in the
LIVER
31
Carriers of the Endogenous Lipids
particularly, TRIGLYCERIDES
VLDL- ENDO
32
There are instances wherein the hydrolysis
(VLDL → LDL) is not complete, this will form
IDL
33
Comes from VLDL if complete hydrolysis.
○ Distribute lipids to peripheral cells.
LDL
34
Excretion pathway will be through stool and
urine, how many percent?
stool- 80%
urine- 20%
35
In digestion, dietary lipids are converted to
amphipathic lipids.
● Amphipathic lipids form micelles in intestinal lumen.
● It occurs when micelles come into contact with
microvillus membranes of intestinal mucosal cells and are absorbed.
1. LIPID ABSORPTION
36
is efficient; greater
than 90% of dietary triglycerides are taken
up by the intestine
TRIGLYCERIDE ABSORPTION
37
After entering the circulation, CMs interact with
proteoglycans on the surface of capillaries such as
skeletal muscles, heart, and adipose tissues.
2. EXOGENOUS PATHWAY
38
Proteoglycans and a specific protein promote the
binding of ______ which hydrolyzes
TAGs in chylomicrons.
LIPOPROTEIN LIPASE
39
Products of hydrolysis of TAGs by LPL that is used as energy source
free FA nd glycerol
40
(further broken down to free cholesterol and amino
acids in the liver)
CM RENANTS
41
VLDL loses core lipids, causing dissociation and
transfer of apolipoproteins and phospholipids to other
lipoprotein particles.
● During this pathway, VLDL is converted to VLDL
remnants, which can be further transformed by
lipolysis into LDL.
● Half of VLDL is converted to LDL; remainder is taken up as VLDL remnants by liver remnant receptors.
3. endogenous pathway
42
Has more triglycerides
chylomicrons
43
One of the major roles of ______ is to maintain the
equilibrium of cholesterol in peripheral cells by the
reverse cholesterol transport pathway.
HDL
44
______removes excess cholesterol from cells.
______can directly deliver cholesterol to the liver.
HDL
45
Another pathway in which HDL mediates the removal
of cholesterol from cells involves what transporter
ABCA1
46
If there is a problem in this pathway, expect that the
color of the stool will be _____
GRAY
47
The net result of these three pathways is the net
delivery of cholesterol to peripheral cells, which can
lead to
ATHEROSCLEROSIS
48
They also synthesize their own cholesterol,
and unlike liver cells, they DO NOT have the
enzymatic pathways to catabolize
cholesterol.
peripheral cells
49
Body’s mechanism to maintain cholesterol equilibrium:
reverse cholesterol transport pathway
50
Which apolipoprotein is responsible for forming
chylomicrons?
apo b-48
51
largest and the least dense(1200 nm)
chylomicrons
52
account to the turbidity of postprandial plasma
chylomicrons
53
readily float on top of plasma (creamy layer)
chylomicrons
54
deliver dietary lipids to hepatic and peripheral cells
chylomicrons
55
Major apolipoprotein of chylomicrons
apo b-48
56
carriers of endogenous TG
VLDL
57
High TG but less than that of CM
VLDL
58
transfer TG from the liver to periphery
VLDL
59
causes turbidity in fasting hyperlipidemic plasma
VLDL
60
The patient fasted = still turbid =
hyperlipidemia
61
from metabolism (lipolysis) of VLDL
LDL
62
transport cholesterol to peripheral tissues
LDL
63
more cholesterol rich
LDL
64
readily taken up by cells via LDL receptors in liver and peripheral cells
LDL
65
If LDL receptor is not functioning, lipid
accumulation in blood vessels occurs,
endogenous synthesis increases
66
The body thinks it is not receiving enough
cholesterol, when in fact there is enough
cholesterol, it’s just that it is not absorbed by
the cells because of the ineffective LDL
receptors. This will _______ the biosynthesis
of cholesterol.
increase
67
proatherogenic lipoprotein
LDL
kapag antiatherogenic = HDL
68
has the capability of producing
atheromatous plaques in arteries
LDL
69
Will benefit from treatment
more than 190 mg/dL
70
With 2 or more CAD risk factors;
more than160 mg/dl
71
Previously diagnosed with heart
● disease; drug therapy should be considered
more than 130 mg/dl
72
smallest and most dense lipoprotein
Core is small and contains more proteins
than lipid.
HDL
73
synthesized by both liver and intestines
HDL
74
with antiatherogenic property
○ It is antiatherogenic because it delivers the
cholesterol to the liver.
HDL
75
capable of transporting excess cholesterol from
peripheral cells to the liver
HDL
76
vehicle for the reverse cholesterol transport –
“good cholesterol”
HDL
77
HDL Exist in two forms:
spherical HDL and discoidal HDL
78
Major types of spherical HDL
HDL 2 and HDL 3
79
larger in. size; less dense; higher lipid; may be
more efficient in the transport of lipids to the liver
HDL2
80
Major apolipoprotein: a1
HDL
81
typically contains 2 molecules of Apo A1
○ represents nascent or newly secreted HDL
○ most active form in removing excess
cholesterol from peripheral tissues
DISCOIDAL
82
exist transiently during the the
conversion of VLDL to LDL
■ Incomplete hydrolysis of VLDL
INTERMEDIATE DENSITY LIPOPROTEIN
83
Initial product or intermediates of VLDL
catabolism –
“VLDL remnants”
IDL
84
Does not accumulate in normal plasma after
an overnight fast
IDL
85
Major apolipoprotein of IDL
apo b 100
86
formed from catabolism of VLDL
○ precursor for LDL synthesis
IDL
87
LDL-like particles but larger and has higher
lipid content
lipoprotein a
88
Concentration________: Increase risk of
premature CHD and stroke
> 30 mg/dL
89
Homologous to plasminogen, thereby
compete for binding sites, promoting clotting
myocardial infarction
90
present in patients with biliary cirrhosis or
cholestasis and in patients with mutations in
lecithin-cholesterol acyltransferase(LCAT)
○ lacks apo B-100
LpX lipoprotein
91
a.k.a the “VLDL-rich in cholesterol”
○ accumulates in type 3 hyperlipoproteinemia
○ more cholesterol than VLDL
B-VLDL
92
due to defective catabolism of VLDL
○ known as “abnormally migrating 𝛃-VLDL”
– has the density of VLDL by ultracentrifugation but migrates with LDL in
the β region during electrophoresis.
B-VLDL
93
density of chylos
<0.93
94
density of VLDL
0.93-1.006
95
density of LDL
1.019-1.063
96
density of HDL
1.063-1.21
97
VLDL on electrophoretic ability
pre beta lipoprotein
98
IDL based on electrophoretic mobility
slow pre beta
99
LDL on electrophoretic mobility
beta lipoprotein
100
diseases associated with abnormal
lipid concentrations
○ Any abnormality in the lipid content
○ due to genetic abnormalities
○ due to environmental/lifestyle imbalances
○ or a consequence of other disease
dyslipidemias
101
Nodules in the skin due to lipid deposits
○ Different from warts (viral infection)
○ Any parts of the body
xanthomas
102
Indicative of the presence of an underlying genetic
abnormality that may lead to dyslipidemia
○ These can be removed but the genetic
abnormality remains
xanthomas
103
High cholesterol in the blood
hypercholesterolemia
104
High TAGs in the blood
hypertriglyceridemia
105
Combined hyperlipidemia with elevated TC
and TG
hyperlipoproteinemia
106
Lipid abnormality most closely linked to heart disease
hypercholesterolemia
107
genetic abnormality predisposing people to elevated cholesterol levels
familial hypercholesterolemia
108
TC = 800-1000 mg/dL(20-26 mmol/L)
■ More severe
○ Heart attack at teenage years
HOMOZYGOTIC FAMILIAL HYPERCHOLESTEROLEMIA
109
treatment of homozygotes
LDL pheresis
110
TC = 300-600 mg/dL(8-15 mmol/L)
○ If not treated, becomes symptomatic for
heart disease in their 20s to 50s
heterozygotic familial hypercholesterolemia
111
treatment of heterozygotic FH
statin
112
In both homozygotes and heterozygotes:
○ High LDL
○ Produce cholesterol normally
○ Deficient LDL receptors
113
no LDL-R synthesis
class 1
114
no LDL-R transport
class 2
115
no LDL to LDLR binding
class 3
116
no LDL-R/LDL internalization
class 4
117
no LDL-R recycling
class 5
118
defect in the LDL receptor gene: reduced LDL binding
familial hypercholesterolemia
class 3
119
normal IC synthesis but deficient LDL
receptors to bind LDL and transfer
cholesterol into cells
familial hypercholesterolemia
120
a result of an imbalance between synthesis and
clearance of VLDL in the circulation
hypertriglyceridemia
121
consequence of genetic abnormalities, or the result of secondary causes, such as hormonal abnormalities
associated with the pancreas, adrenal glands, and
pituitary, or of diabetes mellitus or nephrosis.
hypertryglyceridemia
122
Very high TAG: > 500 mg/dL (can cause acute and
recurrent
PANCREATITIS
MORE THAN 500mg/dl
123
elevated TC (and LDL) and TG
● increased risk for CHD
combine hyperlipidemia
124
high TC and/or TG
○ due to overproduction of VLDL and apo
B-100
familial combined hyperlipidemia
125
due in part to excessive hepatic synthesis of
apoprotein B, leading to increased VLDL
secretion and increased production of LDL
from VLDL
familial combined hyperlipidemia
126
patients may have eruptive xanthomata and
are at high risk for developing CHD
familial combined hyperlipidemia
127
accumulation of cholesterol-rich VLDL and
chylomicron remnants as a result of defective
catabolism of those particles
dysbetalipoproteinemia type 3
128
associated with the presence of a relatively rare form of apo E ________
dysbetalipoproteinemia, apoE2/2
129
dysbetalipoproteinemia TC and TG
TC 200 TO 300
TG 300 TO 600
130
Presence of palmar xanthomas and tuberous and
tuberoeruptive xanthomas
○ premature atherosclerosis in 30 - 50% of
patients (lower extremities)
dysbetalipoproteinemia type 3
131
variant of LDL with an extra apo (a)
Lp(a)
132
with homology with plasminogen
apo (a)
133
absence of Apo A-1
● decreased HDL(<40mg/dL or<1.0 mmol/L)
● increased risk of premature CHD
hypoalphalipoproteinemia
134
Rare autosomal recessive disorder
characterized by markedly reduced or
almost deficient HDL due to a mutation in the
________ gene on chromosome 9
TANGIER DISEASE
ABCA1
135
Low LDL as a result of a defect in the Apo B gene, but because it is not generally associated with CHD,
unless in the homozygous state
hypobetalipoproteinemia
136
due to a defect in the microsomal transfer protein
used in the synthesis and secretion of VLDL
abetalipoprotenimia
bassen-kornzweig syndrome
137
Associated with deficiency of microsomal triglyceride transfer protein(MTP)
abetalipoproteinemia
138
Lipid storage diseases
gaucher’s and niemann-pick disease
139
mutation in the Apo B-100 gene rather than the LDL
receptor
familial defective apolipoprotein b-100
140
resulting in a single substitution of glutamine
for arginine at residue 3500 of apo B-100.
○ substitution reduces the positive charge of
apo B-100 and decreases its affinity for the
LDL receptor.
familial defective apolipoprotein b-100
141
activator of LPL
apo c 2
142
increased LDL- Apo B-100 concentrations with normal
or moderately increased concentrations of LDL
cholesterol
hyperapobetalipoproteinemia
143
creamy layer over clear plasma
high chylomicrons
hyperlipoproteinemia type 1
144
high LDL
CLEAR
type 2A
145
high LDL, VDL
slight turbid
type 2B
146
high b-VLDL or IDL
turbid
type 3
147
HIGH VLDL
turbid to milky
type 4
148
high VLDL, chylomicrons
creamy layer over turbid suspension
tyle 5 hypolipoproteinemia
149
Q3. Among the lipoprotein abnormalities, which one gives a characteristic plasma appearance of creamy layer over a turbid suspension? What lipoproteins are high n this type?
type 5
increased VLDL, chylomicrons
150
Treatment of choice for familial homozygotic
hypercholesterolemia:
LDL phresis
151
More than 500 mg/dL TAG is seen in a patient
pancreatitis
152
Endogenous pathway
○ Doesn’t require fasting
TC
153
From diet
○ Requires fasting
TG
154
storage of lipid
-20 to -70C
155
fasting requirements
12-16 hrs
156
CDC reference method:
abell, levy and brodie
157
Routine Method of cholesterol measurement
cholesterol oxidase
158
Cholesterol + H2SO4 + acetic
anhydride = 3,5 cholestadiene (or
cholestadienyl monosulfonic acid)
■ (green solution)
liebermann-burchard
159
Cholesterol + H2SO4 + ferric
chloride = red end color
PHOSPHOLIPID MEASUREMENT
(cholestadienyl disulfonic acid)
■ (red solution)
salkowski
160
routine method of triglyceride
glycerol kinase
161
CDC Reference Method of triglycerides
modified van handel and zilversmith
162
hydrolysis with KOH ⇒(glycerol + FA)
○ glycerol + periodate ⇒(formaldehyde)
○ formaldehyde + chromotropic H2SO4
solution ⇒ pink chromophore
van handel and zilversmith
colorimetric
163
hydrolysis with KOH ⇒ (glycerol + FA)
○ glycerol + periodate ⇒ (formaldehyde)
○ formaldehyde + acetylacetone + NH3
(yellow)
hantzch condensation
fluorometric
164
Reference method of lipoprotein
ultracentrifugation
165
Supernatant HDL-C by phosphotungstic acid-mgcl2
HDL-C
166
Use of detergents to block HDL and VLDL.
● Measures LDL
direct homogenous assay
167
Limitation: Can’t be used if TG > 400 mg/dL,
so we need to dilute it first before measuring
friedewald equation
