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CardioRenal II > Biochemistry Lipoproteins > Flashcards

Biochemistry Lipoproteins Flashcards

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1
Q

Apoprotein roles

A

1.) Structural role (ampipathic in nature) 2.) Recognition role important in lipoprotein metabolism ( enzymatic regulation of an enzyme, particle recognition for specific receptors)

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2
Q

Tangier disease

A

deficiency of ABCA1- cholesterol cannot be transferred from the plasma membrane to nascent HDL

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3
Q

Familial LCAT deficiency consequences

A

1.) Block in reverse cholesterol transport 2.) limited ability of HDL to acquire cholesterol from VLDL or chylomicrons 2.) Elevated blood cholesterol and triglycerides

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4
Q

Where is VLDL synthesized

A

Liver- assembled in the golgi

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5
Q

lipoprotein exterior

A

ampipathic molecules cholesterol and phospholid

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6
Q

Consequences of Familial Hypercholesterolemia

A

1.) Accelerated CHD (many homozygotes die of CHD by age 20) 2.) Xanthomas (visible subcutaneous lipid depositis that often occur over joints and tendons)

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7
Q

Type III dysbetalipoproteinemia treatment

A

dietary

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8
Q

Discuss what happens when chylomicron binds LPL

A

LPL removes 80-90% of the TAG causing the chylomicron to become smaller. Surface molecules are transferred to HDL (phospholipid, cholesterol, apoproteins A and C) The chylomicron remnant also gains from more apoE and cholesterol ester from HDL

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9
Q

Apoprotein CII

A

LPL cofactor

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10
Q

Apoprotein B-100 role

A

structural- binds LDL receptor

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11
Q

Phospholipid transfer protein (PLTP)

A

A PLASMA PROTIEN. Facilitates transfer of phospholipid from VLDL, IDL, LDL, ect to HDL

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12
Q

Apoprotien associated with LDL

A

ONLY B-100 (also not rich in apoprotein- may explain why its difficult to clear)

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13
Q

Persons with ApoE4 have an increased incidence of what

A

hypercholesterolemia, CHD, and late onset Alzheimer Disease

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14
Q

How is reverse cholesterol transport sill possible with CETP deficienct

A

through cholesteryl ester transport by SR-B1 receptors of liver and through endocytosis of HDL with multiple copies of apoE

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15
Q

Lecithin Cholesterol Acyltransferase (LCAT)

A

transferes fatty acid fron the 2 position of phosphotidylcholine (lecithin) to cholesterol. Synthesized in the liver and secreted into plasma where it becomes associated with HDL and is activiated by apoA-1 (on HDL)

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16
Q

LDL-receptor related protein (LRP)

A

similar to the LDL receptor but not as specific for lipoproteins. Recognizes apoE. NOT significantly affected by intracellular cholesterol

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17
Q

Apoprotien E4

A

associated with an increased risk of hypercholesterolemia and CHD due to increased down regulation of LDL receptoR. HIGHER AFFINITY FOR RECEPTORS

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18
Q

how does the aount of protein within a major lipoprotien correlate to its density

A

increased protien results in increased density

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19
Q

where is HDL synthesized

A

Liver and small intestine

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20
Q

which major lipoprotein is the smallest

A

HDL

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21
Q

80% of chylomicrons go where

A

to heart, adipose and muscle. Remaining 20% is liver uptake

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22
Q

Where are chylomicrons formed

A

formed in intestinal epithelial cells from the digestion of dietary lipids and are assembled in the golgi

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23
Q

which lipoprotein carries lipids synthesized by the liver

A

VLDL

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24
Q

What controls the proteolysis of internalized LDL receptor

A

proprotein convertase subilisin/kexin type 9 (PCSK9)

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25
Symptoms of Type I hyperchylomicronemia
Eruptive xanthomas, abdominal pain after a fat containing meal recurrent pancreatitis
26
Causes of Type I hyperchylomicronemia
deficiency of LPL or apoC-II
27
Hepatic Lipase (HL)
non-convalently bound to heparan sulfate glycoproteins on the sinosoidal surface of liver cells. Hydrolyzed bith TAG and phospholipids
28
Cholesteryl ester tranfer protein (CEPT)
Facilitates transfer of cholesteryl ester from HDL to VLDL, IDL, and IDL. CEPT is synthesized in the liver and secreted into the plasma where it becomes associated with HDL
29
Purpose of HDL
resovoir for apoprotiens and cholesterol reverse transport
30
ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1)
cellular plasma membrane protiens. ATP required- Moves cholesterol from the inner leaflet of the membrane to the outer leaflet (outer leaflet is "available" for the transfer to HDL- important in reverse cholesterol transport )
31
Causes of Type IV hypertriglyceridemia
Primarily lifestyle: obesity, type 2 diabetes, alcoholism, progesterone rich contraceptives, excess dietary carbohydrates (especially sugars)
32
Apoproteins B-48
present only on chylomicrons - plays a structural role
33
Apoprotein(a)
structurally resembles plasminogen but with no plasminogen activity = interferes with fibrinolysis by competeing with authentic plasminogen
34
LDL receptor in the absense of PCSK9
LDL receptor is recycled to the pasma membrane
35
what regulates synthesis of LDL receptor
cholesterol within the cell
36
importance of apoC-III on chylomycrons
inhibit premature removal of chylomicrons from circulation by inhibiting binding to recptors (LDL receptor, LRP, etc)
37
Major lipoprotiens
Chylomicrons, VLDL, LDL, HDL
38
Homozygous Familial Hypercholesterolemia
rare (1/1,000,000) - no functional LDL receptors leading to plasma cholesterol levels of 600-1200 mg/dl
39
Type V hyperlipoproteinemias
RARE. Increased triglycerides, increased cholesterol.
40
One way to distinguish VLDL from chylomicron
Chylomicrons have B-48 and VLDL have B-100
41
Heterozygous Familial Hypercholesterolemia
50% reduction in LDL receptors may double LDL cholesterol
42
Type V hyperlipoproteinemias treatment
dietary
43
Where do nacent chylomicrons get secreted
lymphy
44
HDL3 vs HDL2
HDL3 is smaller and relatively lipid poor - expresses high LCAT activity and removes cholesterol converting it to cholesteryl ester (CE) becomes HDL2 when it has acquired more TAG
45
lipoprotein interior
hydrophobic molecules - triacylglycerols and cholesterol esters
46
Apoproin(a) levels are an independent risk factor for
cardiovasuclar disease
47
which major lipoprotein is the largest
chylomicrons
48
Symptoms of Tangier Disease
Peripheral neuropathy, hepatosplenomegaly, lympadenopathy (only a mild tendenct for early artherosclerosis)
49
fate of chylomicron remnants
binds to Lipoprotein receptors and are cleared from blood by the live. Once internalized the components are metabolized
50
Type III dysbetalipoproteinemia causes
homozygotes for apoE2, low affinity for apoE2 receptor resulting in accumulation of chylomicron and VLDL remanants
51
what promotes LPL synthesis and tranfer to the capillary endothelial cell surface
insulin
52
what tissues express LDL (B-100/E) receptors? Where in these tissues are they expressed?
liver, adrenal glands, and gonads. Liver is most important. LDL receptor is found in claterin coated pits
53
what tissues express apoE
liver, brain, and placenta
54
importance of apoC-II on chylomicons
required for LPL activity
55
Nacent HDL
disc shaped, phospholipid rich praticle with apoprotiens- from liver (A-I , A-II, E, and C) OR from the intestine (only A-I)
56
which lipoprotien carries out reverse transport (what is reverse transport)
HDL- takes cholesterold from extrahepatic tissues back to the liver
57
Lipoprotein Lipase (LPL) location
NOT EXPRESSED BY ADULT LIVER. Anchored to the surface of capillary endothelial cells of adipose, skeletal muscle and heart muscle through a non-covalent interaction with glycosylphoshatidylinositol-anchored high density lipoprotein bidning protein 1 (GPIHBP1)
58
apoproteins present on nacent chylomircons
apoA proteins and apoB-48
59
Abetalipoproteinemia consequences
severe fat malapsorption (cant form chylomircons from dietary intake) accumulation of triglycerides in intestine and liver, deficiencies of fat soluble vitamins (carried in chylomicrons)
60
Consequences of Tangier Disease
Mature HDL cannot be formed, decreased LDL (no transfer of cholesteryl ester to VLDL from HDL), cholesteryl ester deposits in reticuloendothelial cells, bone marrow, schwann cells (cant get rid of cholesterol)
61
What do Chylomicrons carry
lipids from the digestion of food stuffs
62
What makes up a lipoproteins
HYDROPHILIC LAYER: Protien. Phospholipid HYDROPHOBIC LAYER: triacylglycerols, cholesterol and cholesterol esters
63
Type III dysbetalipoproteinemia
RARE. Increaed triglycerides, increaed cholesterol. Symptoms include xanthomas and increased risk of CHD
64
IDL
VLDL remnant - 50% cleared by the liver , 50% not cleared and remodeled to form LDL
65
apoproteins
proteins associated with lipoproteins
66
Familial hypercholesterolemia
AUTOSOMAL DOMINANT - deficienct in LDL receptor
67
Is cholesterol esterase ampipathic
no- only lipid soluble
68
apoproteins present on newly synthesized VLDL
apoB 100 and small amounts of apoE ad apoC f
69
Apoprotien E2
associated with familial dysbetalipoproteinemia due to less efficienct clearance of VLDL and chylomicrons. LOWER AFFINITY FOR RECEPTORS
70
LPL tissue Km - what is the significance of this
large Km in adipose and small Km in the heart - Significance: heart gets first crack at it- only when you have excess (high amounts) does it go to adipose tissue (store excess as fat)
71
where do you find the highest concentration of Lipoprotein lipase (LPL)
in the heart
72
Familial LCAt deficiency symptoms
Free cholesterol accumulates in most tissues, kidney disease, corneal clouding , mild tendency for early atherosclerosis
73
Untreated Abetalipoproteinemia leads to
Ataxia, retinitis pigmentosa, myopathy
74
\*\* LDL (B-100/E) receptor \*\*
plasma membrane receptor found in clathrin coated pits. LDL binds receptor and results in internalization of LDL and further metabolism of its contents
75
CETP deficiency
BENIGN- common in Japan. Cholesteryl esters cannot be transferred from HDL to other lipoproteins. Homozygotes may have 4x elevation of HDL cholesterol, LDL cholesterol is normal and low
76
which major lipoprotein is the most dense
HDL
77
Type IV hypertriglyceridemia
COMMON. Increased triglycerides and usually some hypercholesterolemia due to cholesterol content of VLDL
78
Lipoprotein lipase (LPL) function
1.) catalyzes step wise hydrolysis of triacylglycerol to glycerol and 3 NEFA.
79
Fate of VLDL remanants
1.) Some go to liver 2.) Some get attached to liver hepatic lipase 3.) some are lost 4.) some associate with B100 to form LDL
80
clearance of LDL
70% by liver (LDL receptor, LRP receptor) 30% by extrahepatic tissues (ex: adrenals use cholesterol to form steroid hormones)
81
HDL purpose
1.) serves as a resovoir for apoproteins needed by nascent chylomicrons and nacent VLDL 2.) reverse cholesterol transport
82
Abetalipoproteinemia
deficiency of triglyceride transfer protein in the endoplasmic reticulum. Liver and intestine are unable to assemble or secrete apoB-containing lipoproteins - chylomicrons, VLDL and LDL essesntially absent
83
Chylomicrons are composed of mostly what
triacylglycerides
84
which lipoprotien carries lipids from digestion
chylomicrons
85
Lp (a)
modified LDL- B-100 with apoprotein(a) covalently bound via disulfide bond
86
Causes of Type V hyperlipoproteinemias
increased chylomurons and VLDL. Associated with uncontrolled diabetes and kidney disease.
87
Which apoproteins do chylomicrons accumulate in the blood? What is the source of these apoprotiens?
apoC (I and II) and apoE from circulating HDL
88
how are apoprotein(a) levels determined
genetically - derived from its own gene (LPA) which is thought to have evolved from the plasminogen gene (PLG)
89
Apoprotein E function
binds to LDL receptor
90
which major lipoprotein is the least dense
chylomicrons
91
Type II hypercholesterolemia
COMMON. Elevated LDL cholesterol caused by familial hypercholesterolemia. Seconday causes are more common and include obesity and diabetes. Major risk pattern for atherosclerosis
92
LDL metabolism
long plasma halflife (up to several days)
93
Apoprotein A1 function
activates LCAT
94
Type I hyperchylomicronemia
increased triglycerides (up to 1000 mg/dl), slightly elevated cholesterol, NOT associated with increased atherosclerosis
95
when is the only time chylomicrons are present in the body?
after a meal - half life is less than 1 hour
96
Treatment of Abetalipoproteinemia
clinical signs respond to treatment with vitamin E
97
Scavenger receptor B1 (SR-B1)
binds HDL via apoA-1 - transderes cholesteryl esters from HDL from liver. Mostly expressed in the liver
98
What do VLFL carry
lipids synthesized by the liver
99
LDL receptor fate in the presence of PCSk9
More destruction/downregulation of the LDL receptor - less LDL is brought into the liver = Hyperlipidemia
100
Treatment of type I hyperchylomicronemia
low fat diet

CardioRenal II (12 decks)

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