Blood Lipoproteins Lec 2 Flashcards

1
Q

What are the lipoprotein complexes?

A
Chylomicrons
very low density lipoproteins (VLDL)
intermediate density lipoproteins (IDLs)
low density lipoproteins (LDLs)
hight density lipoproteins (HDLs)
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2
Q

What is the purpose of lipoproteins?

A

to protect their hydrophobic cargo from aqueous env. while shuttling from tissue to tissue

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3
Q

What is in the core of the lipoprotein (the hydrophobic core)?

A

Triacylglycerol (TAG)

cholesterol esters

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4
Q

how is the density determined for lipoproteins?

A

protein to lipid ratio–ex: chylomicrons contain the highest % of lipid (primarily TAG) and the lowest % protein

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5
Q

When performing electrophoresis which lipoprotein particle is going to travel the furthest and which the least?

A

Furthest—HDL

Least– chylomicron

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6
Q

When performing ultracentrifugation which lipoprotein will sit on top and which will be at bottom?

A

Top- chylomicrons

bottome- HDL3

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7
Q

What are some of the functions of apoliproteins?

A

sites for cell surface receptors
enzyme activators involved in lipoprotein metabolism
some–structural components of the lipoprotein

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8
Q

Apo A-I-where is it synthesized and whats its function?

A

Liver and intestine

Structural protein in HDL

Activates LCAT- Transfers FA from lecithin to cholesterol to generate CE

Involved in RCT–transfer of cell cholesterol by ABCA1 to nascent HDL and delivery to liver

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9
Q

What is LCAT and what activates it?

A

transfers a FA from lecithin to cholesterol to generate CE–activity involved in maturation of HDL

Apo A-I activates it

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10
Q

Apo A-II where is it synthesized and whats its function?

A

Liver

Structural protein- HDL

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11
Q

Apo B-100 where is it synthesized and whats its function?

A

Liver
Structural protein-VLDL/LDL
VLDL assembly
LDLR binding

measurements of api B-100 in plasma reflect particle number and higher levels are associated with CVD

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12
Q

Apo B-48 where is it synthesized and whats its function?

A

Intestine

Chylomicron formation and secretion

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13
Q

Apo C-I where is it synthesized and whats its function?

A

Liver

LCAT activator–transfers FA from lecithin to cholesterol to generate CE–maturation of HDL

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14
Q

Apo C-II where is it synthesized and whats its function?

A

Liver

LPL activator

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15
Q

Apo C-III where is it synthesized and whats its function?

A

Liver

LPL inhibitor

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16
Q

Apo E (E2, E3, E4) where are they synthesized and whats their function?

A

Recognition by LDL and CM remnant receptors–mediates the hepatic uptake of CM and VLDL remnants as well as IDL

Responsible for clearance of intestinal derived LPs after a meal and for the clearance of VLDL and IDL before they are covered to LDL

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17
Q

What Apo E is a risk for dysbetalipoproteinemia (type III hyperlipidemia) ? and what is seen in the plasma?

A

Apo E2–characterized by elevation of CM and VLDL remnants in the plasma

18
Q

Apo(a) where is it synthesized and whats its function?

A

Liver

modulates thrombosis/thrombolysis

19
Q

Where are the enzymes involved in the synthesis of the TAG, cholesterol and phospholipids found for chylomicron metabolism?

A

Smooth ER–> microsomal triglyceride transfer protein (MTP)–loads Apo B-48 with lipid

20
Q

What enzyme loads Apo B-48 with lipid?

A

microsomal triglyceride transfer protein (MTP)

21
Q

When the nascent chylomicron reaches the blood it receives what?

A

Apo-E and Apo-C

22
Q

What does Apo-C II come in contact with in the blood and what does this cause?

A

LPL–activation

-hydrolyzes TAG–yielding fatty acids/glycerol

23
Q

What occurs after the FAs are formed and all thats left is a chylomicron remnant?

A

Remnant taken up by liver by Apo-E binding to specific lipoprotein receptors followed by endocytosis/lysosomal hydrolytic enzymes degrading remnant components to cholesterol/AAs/FAs

24
Q

Where does Apo C-II bind to the LPL?

A

The C terminal domain–provides specificity

25
In the fed state (elevated insulin) adipose tissue does what and muscle tissue does what? what occurs in the fasted state?
Adipose tissue--LPL expression is increased Muscle-- LPL is decreased Fed-- Adipose LPL decreased Muscle--LPL increased
26
When pts have deficiency of LPL or Apo C-II what occurs and what are the pts at risk of?
Type 1 hyperlipoproteinemia/familial LPL deficiency Accumulation of chylomicron TAG in plasma Higher risk for pancreatitis
27
What Nascent particles are present on VLDLs after they are produced by the liver?
Apo B-100
28
What do HDL particles supply to VLDLs?
Apo E and Apo C-II
29
What does cholesterol ester exchange protein (CETP) facilitate?
Exchange of TAGs from VLDL to HDL for cholesterol esters Greater concentration of TAG contacting lipoprotein parcels in blood the greater the exchange
30
How does nonalcoholic fatty liver (hepatic steatosis) occur?
conditions where there is an imbalance btwn TAG synthesis and secretion of VLDL
31
What do pts with homozygous E2 deficiency have? | What occurs in these pts?
can't clear chylomicrons or IDL--this is type III hyperlipoproteinemia hypercholesterolemia and premature atherosclerosis
32
Apo E-4 is related to what dz?
Alzheimer's
33
If cholesterol is not needed right away what occurs and how does it occur?
Cholesterol is estterified by Acyl CoA: cholesterol acyl transferase(ACAT) get increased ACAT activity with increased intracellular cholesterol + fatty acid to C3--replaces OH to form cholesterol ester
34
What is the function of the LDL particle?
to provide cholesterol to the peripheral tissues and return it to the liver
35
What do LDL receptors recognize on the LDL particles?
Apo B- 100 and Apo E
36
What is type II hyperlipidemia/familial hypercholerolemia?
Deficiency of LDL receptor--causing elevated plasma LDL-cholesterol
37
What causes the conformational change causing release of LDL from it receptor?
ph dependent conformational change at region 2 of the LDL receptor
38
Where and how are HDLs formed?
formed in blood by addition of lipids to api A-1 which is synthesized in the liver and intestine and secreted in the blood
39
What does HDL supply?
circulating supplier of api C-II and Apo E
40
What is Tangier disease?
rare deficiency in ABCA1--leading to absence of HDL particles because of degradation of lipid-free apo A-I
41
What is reverse cholesterol transport?
Transfer of cholesterol from peripheral cell to HDL--from HDL to liver for bile acid/salt synthesis