Plasma Lipoproteins & HDL Physiology Flashcards

1
Q

What are triacylglyerols made up of?

A

Glycerol and 3 fatty acids

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2
Q

What are phospholipids made up of?

A
Glycerol and 2 fatty acids
Phosphorous group (polar)
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3
Q

What are the main types of lipids?

A
  1. Triacylglycerol
  2. Phospholipids
  3. Cholesterol
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4
Q

What is cholesterol a precursor for?

A
  • bile salts
  • steroid hormones
  • vitamin D
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5
Q

Esterification of fats

A

FFAs to triacylglyerols

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6
Q

Hydrolysis of fats

A

Triacylglyerols to FFAs

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7
Q

What is the total recommended cholesterol?

A

< 4.0mmol/L

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8
Q

Which is the bad cholesterol?

A

LDL

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9
Q

What are lipoproteins composed of?

A
  1. Apoproteins
  2. Phospholipids (outside)
  3. Triacylglyerols
  4. Free and esterified cholesterols
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10
Q

What are the classes of lipoproteins?

A
  1. Chylomicrons
  2. VLDL
  3. IDL
  4. LDL
  5. HDL
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11
Q

As lipoproteins get smaller, the amount of triacylglyerols ………… and they become more ……………

A

Decreases, dense

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12
Q

Why are LDL’s bad?

A

Have a long plasma half-life

If they become oxidised they have a greater capacity to form foam cells and contribute to atherosclerosis

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13
Q

What enters the liver after the cholymicron passes through the circulation?

A

Cholymicron remnant

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14
Q

Which type of lipoproteins does the liver release?

A

VLDL

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15
Q

What does HDL do?

A

Removes cholesterol from peripheral cells

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16
Q

Apoproteins have a ………. role in cholymicron

A

Structural

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17
Q

What does apoC-II do?

A

Allows release of lipids from cholymicrons (exogenous) and VLDL (endogenous)

Co-factor for enzymes of lipid metabolism - causes hydrolysis

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18
Q

ApoB-48

A
  • found on cholymicrons
  • synthesised in intestines
  • lack receptor binding domain
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19
Q

ApoB-100

A
  • found on VLDL and LDL
  • synthesised in liver
  • binds to LDL receptors
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20
Q

How are lipoproteins (cholymicrons and VLDL) formed? (5)

A
  1. FFAs move into cell
  2. Need to be esterified in smooth endoplasmic reticulum (by the enzyme ACAT)
  3. Components are packaged together by MTP (micro so al transfer protein
  4. Transferred to Golgi apparatus where they become glycosylated
  5. Excocytosed into circulation (CM into lymphatics, VLDL into blood)
21
Q

Where is lipoprotein lipase present? (4)

A

Adipose
Muscle
Mammary gland
Heart

22
Q

What are the characteristics of LDL?

A
  • main carrier of cholesterol
  • ApoB-100 is the only apoprotein present
  • long plasma half-life of 3 days
  • atherogenic
23
Q

LDL receptor pathway

A
  1. ApoB-100 allows binding at BE (LDL) receptor
  2. Endocytosed
  3. Broken down by lysosomes
  4. Releases free cholesterol
24
Q

What are the 3 important roles of cholesterol in cells?

A
  1. Down regulation of cholesterol synthesis through decrease in HMG CoA reductase
  2. Storage of CE in cells through increase in ACAT
  3. Down regulation of receptor expression (decrease in LDL uptake)
25
What is the function of cholesterol?
- part of all cell membranes - gene regulator - regulator of fetal development - precursor for vitamin D, bile salts, steroid hormones
26
Cholesterol homeostasis: diet
0.5g/day
27
Cholesterol homeostasis: synthesis
1g/day
28
Cholesterol homeostasis: secretion into bile
1g/day
29
Cholesterol homeostasis: convert to bile salts
0.5g/day
30
Cholesterol homeostasis: secretion into VLDL
1g/day
31
What transports cholesterol into cells?
C transporters
32
What transports cholesterol out of cells?
ABCs | ATP-binding cassettes
33
ABCA1 transporter
Transports cholesterol out of cells into HDLs
34
ABCG5/8 transporter
Transports cholesterol into gut lumen/bile
35
What does cholesterol ester transfer protein allow?
Transport of cholesterol between lipoproteins LDL to HDL
36
The absorption of dietary cholesterol is.........
Very poor, 50%
37
Some of the cholesterol that is absorbed by the gut gets..........
Pumped back out again by ABCG5/8
38
What does the NPC1L1 transport protein do?
- cholesterol transport into cells | - blocked by Ezetimibe
39
Plant sterols compete with .......... for absorption
Cholesterol
40
How is cholesterol excreted in the liver?
1. Taken up in hepatocyte by SR-B1 (HDL) or LRP1 2. Hapatocytes also express LDL receptor 3. Converted to bile salts 4. Transported by bile salt export pump (BSEP) 5. Free cholesterols pumped out by ABCSG5/8 6. Bile salts taken up by apical sodium dependent bile salt transporter (SDBST) in enterocytes
41
What are the 5 steps of cholesterol biosynthesis?
1. Acetyl CoA converted to HMG-CoA via HMG-CoA synthase 2. HMG-CoA is converted to mevalonate by HMG-CoA reductase (rate limiting step) 3. Mevalonate is converted to isopentenyl pyrophosphate (IPP) 4. IPP converted to squalene 5. Squalene converted to cholesterol
42
Cholesterol slows down cholesterol biosynthesis by ........
Inhibiting expression of HMG-CoA reductase
43
What regulates the expression of genes related to cholesterol control?
SREBP transcription factor | Cleaved and activated by SCAP
44
How do statins reduce cholesterol?
Down regulate expression of MHG-CoA reductase | Has other pleiotropic effects (high up enzyme)
45
What is reverse cholesterol transport?
HDL picks up LDLs and transports them back to the liver and cholesterol can be recycled
46
What is the process of reverse cholesterol transport? (5)
1. Nascent HDL structures 2. HDL take up CE and phospholipids from peripheral cells via ABCA1 3. Lipid loaded HDL converted to mature plasma HDL by LCAT - possible because of Apo-A1 4. CE can be exchanged between lipoproteins by CETP 5. HDL particles taken up by SR-B1 receptor in liver and adrenal glands
47
Why is HDL good? (4)
1. Inhibits recruitment of macrophages to arteries 2. Inhibits arterial smooth muscle proliferation 3. Inhibits arterial smooth muscle contraction 4. Mediates transport of cholesterol from cells via cholesterol reverse transport
48
What do lipoprotein lipases do?
Cause hydrolysis