Lipoprotein handling Flashcards
1
Q
what is triglyceride made out of
A
3 fatty acids and glycerol
2
Q
how is a triglyceride made
A
- made by esterification
3
Q
why use free fatty acids as an energy store
A
- they are the major fuel for metabolism
- they are the immediate source of energy
- there oxidation produces a higher ATP than the oxidation of carbohydrates and proteins
4
Q
How are triglycerides transported in the blood
A
- triglycerides are hydrophobic therefore they are no readily transported in the blood
- packaged into lipoproteins - these use cholesterol and proteins
5
Q
where is TAG stored
A
- Liver and adipose tissue
6
Q
what is the purpose of lipogenesis
A
converts acetyl-CoA to fatty acids
- via lipogenesis and triglyceride synthesis energy can be efficiently stored in the form of fats
7
Q
whereas does lipogenesis take place
A
- adipose tissue
- liver
- cytosol of cells
8
Q
what do lipoproteins do
A
- the transport of TAG, cholesterol and phospholipids between different organs and tissues.
- they also trnsport some vitamins
9
Q
what are lipoproteins made by
A
hepatocytes and enterocytes
10
Q
what is the inner core of the lipoproteins made form
A
inner core is hydrophobic
- cholesterol esters and TAG and located in the core
11
Q
what is the outer core of lipoproteins made out of
A
- phospholipids
- free cholesterol
- apoproteins (these different between lipoprotein)
- outer core is hydrophilic
12
Q
what are two different types of apoprotein s
A
embedded (apoB) or loosely bound (apoC)
13
Q
what do apoproteins do
A
they determine the role of lipoproteins (cellular interaction)
- they activate and inhibit enzymes in lipoprotein metabolism
- Ligands for the cellular apoB/E (LDL) receptors and scavenger receptors
14
Q
what receptors are responsible for LDL clearance
A
ApoB/E receptors & scavenger receptors are responsible for LDL clearance
15
Q
what are the 5 major types of lipoproteins
A
chylomicrons VLDL IDL LDL HDL
16
Q
what is the order of apopprotiens from least dense to most dense
A
chylomicrons VLDL IDL LDL HDL
17
Q
what is the main component of chylomicrons and what apoprotein does it have
A
TAG
B48 A C E
18
Q
what is the main component of VLDL and what apoprotein does it have
A
TAG
B100 A C E
19
Q
what is the main component of IDL and what apoprotein does it have
A
TAG and cholesterol
B100 E
20
Q
what is the main component of LDL and what apoprotein does it have
A
Cholesterol
B100
21
Q
what is the main component of HDL and what apoprotein does it have
A
Protein
AI AII C E
22
Q
What does Apo B100 do
A
- it controls the metabolism of LDL
- it is truncated from apoB48
23
Q
what does APO B48 do
A
controls chylomicrons
24
Q
what does APOE do
A
- controls receptor binding of remnant particles
25
what does Apo C do
it acts as an enzyme inhibitor
26
what happens to chylomicrons
- chymicrons originate from the enterocytes
- chylomicrons are then converted to IDL it can then be converted to TAG by lipoprotein lipase
- or it can then be converted back to the liver
- or it can be converted to LDL
27
what happens to LDL
- LDL is even converted to cholesterol to cells or it is converted back to the liver
28
what happens to HDL
HDL is produced by the liver , it then picks up excess cholesterol from the peripheral tissue to the liver for disposal
29
what colour is someones blood who has just eaten fat blood plasma
Dietary fat goes into blood plasma and this makes it more cloudy
30
describe how chylomicrons are used
- Gut loads both the fatty acids and cholesterol into the lipoproteins called chylomicrons
- They contain Apo protein B48
- The chylomicrons then flow through the circulation
31
what do chylomicrons interact with
- interact with peripheral tissue, this contains lipoprotein lipase this allows the chlyomicrons to deposit the contents of the chylomicrons into the tissue
- it also interacts with HDL, they swap the app proteins, this increases the levels of Apo protein CII and increases the level of app protein E
the Apo protein E targets it from disposable therefore the liver takes it out of circulation
32
what do lipoprotein lipase do
- They interact with chylomicrons and VLDL
| - Breaks it into free fatty acids and glycerol and these can be taken up by cells and used to store fat
33
what app protein activates lipoprotein lipase
Apo Protein C2
34
what happens after you eat a meal to lipoprotein lipase
- after a meal LPL activity is high in adipose tissue
- therefore most fatty acid from TAG is chylomicrons are targeted to adipose tissue for etherification and storage
- the remnants are then metabolised by the liver
35
what is the half life of chylomicrons
less than 1 hour
36
what happens duration starvation to lipoprotein lipase
- LPL activity is high in muscle
- therefore FA derived from TAG in VLDL and is mainly fed into oxidation therefore it makes acetyl- CoA and enters the TCA cycle
37
what does ApoA do
- efflux of cholesterol from peripheral cells and the influx of cholesterol into hepatocytes
38
What does ApoB do
ApoB100 and ApoB/E receptors cause cellular uptake of LDL - it is derived from liver and forms part of LDL
- Apo B48 is derived from the gut and is found in chylomicrons
39
what does ApoC do
- made in the liver
- it is the peripheral activator of LPL
- transferred between lipoproteins
40
what does ApoE do
- stabilises VLDL, ILDL and remnant particles causes cellular uptake
- ligand for the Apo B/E receptor
41
what makes up the fatty acids in the diet
- most fatty acids are supplied by the diet
- 90% is in the form of triglyceride
- cholesterol
- cholesterol ester
- phospholipids
- free fatty acid
42
what are dietary TAG lipoproteins packaged into
chylomicrons
43
how is liver derived TAG released
- it is releases as VLDL
44
where is lipoprotein lipase situated (lipoprotein metabolism)
- it is situated on the endothelium adjacent to target cells
- it is the gatekeeper of lipoprotein metabolism
45
describe what happens to low density lipoproteins
- after their secretion VLDL acquires cholesterol easter and apoproteins ApoC and ApoE from HCL
- They are hydrolysed by LPL and this makes VLDL remnants called IDL
- the conformation of ApoB100 and ApoE in VLDL prevents them binding to the LDL (APOB/E) recemport
- in remnants ApoE assumes a conformation that allows them to bind to the LDL receptor
- there is a liver enzyme (hepatic TAG lipase_ this makes IDL transform into the rich LDL
- LDL only contains one type of apoprotein which is ApoB100
- It therefore lacks ApoE so this means that it remains in the circulation for longer and is eventually taken up by the liver or peripheral tissues
46
what does cholesterol do
- it is an essential component of cell membranes
- storied
- bile synthesis
47
what regulates cholesterol
HMG-CoA reductase
48
what regulates the expression of HMG-CoA reductase and the LDL receptor
SREBP - this regulates the expression of HMG-CoA reductase and the LDL receptor
49
how does LDL uptake occur
- occurs when intracellular cholesterol levels delicate
- LDL uptake occurs by the LDL ApoB/E receptor on the plasma membrane
- this causes the formation of cholesterol being release and esterified within the cell
50
what can HDL do
- it can exchange components with other lipoproteins and are in the liver and intestine
51
what structures are HDL
- they are formed as discoid, lipid poor particles containing mainly ApoA1
52
what does HDL do and how does it do it
- HDL transports cholesterol from peripheral tissues to the liver for disposal via bile
- HDL binds to the scavenger receptors and transfers cholesterol into the cell membrane
- the redundant parts of HDL then take part in the next transport
also
- HDL scavenges free cholesterol from cell membranes via ABCA1 transporter (a membrane protein) and esterfieis it to cholesterol esters
53
is LDL or HDL a risk to cardiovascular disease
- LDL is a risk for cardiovascular disease whereas HDL is cardio protective
54
what can elevate HDL
- moderate alcohol consumption
| - regulate aerobic exercise leads to elevated HDL levels
55
what is high TAG levels linked to
- atherosclerosis
- stroke
- CHD
56
what is more at risk high LDL levels or high TAG levels
- high LDL levels
57
what does smoking and diabetes do to LDL
- oxidised LDL which is generated by smoking and diabetes cause the formation of atherosclerotic plaques
58
how does oxidised LDL cause plaques to form
- oxidised LDL binds to scavenger receptors rather than the LDL receptor in macrophages
- scavenge receptors are not feedback regulated by cholesterol, this causes macrophages to become lipid laden and form foam cells
- this leads to the formation of fatty streaks in the arterial wall leading to plaque formation
59
what is an LDL treatment
- statins
60
what do statins do
- comeptivie inhibitor of HMG=CoA reductase
| - this lowers in cell cholesterol and therefore takes up more LDL
61
what is the mechanism of action of LDL cholestryamine
- binds bile acids in the gut preventing enterohepatic circulation
62
what are the LDL cholestryamine eadverse effects
- gastrointestinal adverse effects
| - nausea, abdominal boating, alteration of bowel habit flatulence
63
what is the lipid lowering effect of LDL cholestryamine
- 8-15% reduced in LDL, little or not effect on HDL cholesterol
- results in a rise of TAG concentration
64
what is the long term safety of LDL cholestryamine
- not systemically absorbed - therefore safety is good
| - supplements of fat soluble vitamins may be required
