Lipid transport in blood Flashcards
(94 cards)
1
Q
overview process of fuel storage (basic)
A
- energy providing foods are consumed in greater quantities than needed at the time
- excess energy is stored
- CHO stored as glycogen, but store limited as liver glycogen dissapears overnight
- long term fuel store is lipid as TAG
- lipid storage is not limited = we get fat
2
Q
what fuel store is limited
A
CHO as glycogen
3
Q
what fuel store isnt limited
A
lipid as TAG
4
Q
what is TAG
A
triacylglycerol
- glycerol phosphate
- 3 x fatty acids
5
Q
where does TAG synthesis occur
A
in nearly all cells
but mostly in the liver, SI and adipose
6
Q
what is glycerol phosphate
A
active form of glycerol and comes from glycolysis.
the phosphate group leaves once TAG is formed
7
Q
state of TAG
A
completely hydrophobic and therefore will NOT circulate
8
Q
how are TAGs made hydrophillic
A
addition of apoproteins and other lipids such as plp c and VLDL
9
Q
plp c
A
phospholipid cholesterol
10
Q
VLDL
A
very low density lipoprotein
11
Q
lipoprotein structure
A
outer shell:
- singles layer of phospholipids, cholesterol and apoproteins
inner shell:
- TAG and cholesterol esters
12
Q
what are the hydrophilic parts of lipoprotein
A
phospholipids
cholestorol
apoproteins
13
Q
what are the hydrophobic parts of lipoprotein
A
TAG
cholesterol esters
14
Q
state of phospholipids
A
hydrophilic, charged and polar
15
Q
state of cholesterol
A
hydrophillic and polar
NOT charged
16
Q
purpose of lipoprotein
A
allows lipid, which is insoluble in water, to be transported as a lipoprotein complex
17
Q
role of apoproteins
A
- don’t function on their own
- structural role as they are onthe outside of lipoprptein bc hydrophillic
- recognised by receptors on cell surfaces
- activate certain enzymes in lipid metabolism
- important for transport and storage
18
Q
classes of lipoproteins
A
chylomicrons
VLDL
LDL
HDL
19
Q
how do classes of lipoproteins vary
A
more fat = lower density
20
Q
chylomicrons
A
- largest and lowest density lipoprotein
- carry mainly TAG
21
Q
VLDL
A
- very low density lipoprotein
- carries mainly endogenous fat/TAG
22
Q
LDL
A
- low density lipoprotein
- carries mainly cholesterol to the tissue
- BAD CHOLESTEROL
23
Q
HDL
A
- high density lipoprotien
- carries mainly cholesterol, from the tissue to the liver
- cholesterol is taken to liver for excretion
- GOOD CHOLESTEROL
24
Q
what apoproteins are found on chylomicrons
A
apo B48
found in the intestine; fat that we eat
48 AA
25
what apoproteins are found on VLDL
apo B-100
| 100 AA
26
what apoproteins are found on LDL
apo B-100
| 100 AA
27
B-100
- apoprotein found on VLDL and LDL
- important for receptor recognition
- 100 AA
28
B-48
- apoprotein found on chylomicrons
- structural role
- 48 AA
29
apo-E
- apoprotein on chylomicron remnants
- important for receptor recognition
- or from HDL
30
apo C-11
activates LPL
| - on chylomicrons
31
apo A-1
activates LCAT
| - on HDL
32
How do apoproteins work as destination-targeting signals
- bind to specific receptors on the surface of cells
- binding leads to uptake of the lipoprotein bound to apo
- uptake is receptor-mediated endocytosis
= individual lipoproteins are taken up only by designated cells for specificty
33
what is the uptake method for lipoproteins in to cells
receptor-mediated endocytosis
34
LPL
lipoprotein lipase
35
apoproteins that activate enzymes
apo C-11 on chylomicrons activates LPL
= removes fatty acids from TAG
apo A-1 on HDL activates LCAT
= forms cholesterol in peripheral cells and phospholipd on HDL itself, and carries as ester to the liver
36
current average fat intakes
~80g per day
| needs to be reduced by 30%
37
what activates LPL
- apo C-11
| - insulin in absorptive state
38
Transport of lipid from the gut: exogenous fat
- fat eaten
- TAG from SI joins with apo-E and apo C-11 from HDL in cirucaltion to form chylomicron for cirucaltion
- LPL on capillary lining is activated by apo C-11 and insulin in absorptive state, and hydrolyses TAG
- TAG cannot move across membrane, but FA can
- FA cross to adipose where re-esterified using GP from glycolysis
- glycerol from TAG is inactive, and goes to liver where glyerol kinase activates it
- of the remaining chylomicron:
- apo C-11 returns to HDL
- apo E binds to recepto on liver causes chylomicron remnant to be internalised and reused
39
Transport of lipid from the gut: endogenous fat
similar to the process of exogenous liver, but starts from VLDL in the liver
- VLDL has b-100, but also picks up C-11 and E from HDL
- LPL on capillary lining is activated by apo C-11 and hydrolyses TAG
- TAG cannot move across membrane, but FA can
- FA cross to adipose where re-esterified using GP from glycolysis
- glycerol from TAG is inactive, and goes to liver where glyerol kinase activates it
- of the remaining VLDL is becomes IDL, and apo E and C-11 return to HDL
- IDL is now LDL with just B-100 apoprotein, consisting of mostly cholesterol
- 50% of LDL will go to the liver via B100 receptor
- 50% of LDL will go to periphery by B100 receptor
40
what does defective b100 receptor cause
high blood cholesterol
41
cholesterol synthesis
we do not need cholesterol from the diet becuase we can biosynthesis it
- if diet provides cholesterol, biosynthesis is reduced and number of b100 receptors on cell surface
42
control of cholesterol synthesis
- nucleus makes LDL receptors
- B-100 on LDL binds to receptor and whole of LDL is internalised
- lysosome forms and cholesterol is released along with proteins from LDL
- cholesterol release effects the nucles to stop synthesis of enzymes used to synthesis cholesterol
= balance between diet and biosynthesis
- vegans rely on biosynthesis
43
who relies on cholesterol biosynthesis
vegans
44
LDL receptors
- very important
- recognises B-100 on LDL
- remove LDL and hence cholesterol from circulation
= receptor mediated endocytosis
45
LDL receptor deficiency
= familia hypercholesterolemia
- very high blood cholesterol levels
- premature death from atherosclerosis (8yrs!!)
46
how is cholestoerl synthesised (biochem prcess)
- acetyl CoA + acetoacetyl CoA -> HMG-CoA
- HMG-CoA -> mevalonate = rate limiting step
needs HMG-CoA reductase
- mevaolonate -> cholestorel
47
what is the rate limiting step of cholesterol synthesis
- HMG-CoA -> mevalonate = rate limiting step
| needs HMG-CoA reductase
48
enzyme needed for cholesterol synthesis
HMG-CoA reductase
49
how is cholesterol reduced therapeutically
statins
50
how do statins work
statins ihibit HMG-CoA reductase, and therefore decreases cholesterol synthesis in cells
- this allows liver and periphery to take up more cholesterol from the circulation
- 0.5g/day is removed from circuation by liver in the form of bile salts
51
what does removal of cholsterol from circulation by liver from
bile salts
52
alternative approaches for reducing total LDL cholesterol
- inhibitors of cholesterol absorption
- bile acid sequestering agents
= prevent reabsorption from the intestine
53
LCAT
lecithine cholesterol acyltransferase
- transfers acyl group (FA) from lecithine and puts it on cholesterol
LCAT AKA PCAT
lecithine = phosphatidylcholine
54
descirbe HDL
- high density lipoprotein
- HLD are good cholesterol
- made in SI and liver
- flat and hollow inside
- comes with Apo- A1
55
role of HDL in cholesterol transport
- HDL goes to peripheral cells to remove cholesterol
- LCAT is activated by apo-A1 on HDL
- LCAT removes a FA from lecithine to bind to cholesterol and transport from periphery to HDL
- cholesterol ester is formed and buried inside HDL bc neutral
- Most cholesterol ester then taken to liver for excretion
- some CE is offloaded to VLDL to allow HDL to continue removal of cholesterol
- this is becuase build up of CE in HDL inhibits LCAT
56
CETP
cholsterol ester transfer protein
57
what does CETP do
CETP allows the offloading of CE to other lipoproteins
- HDL transfers CE to LDL, IDL and VLDL
- IDL and LDL deliver contents to extrahepatic tissues but a proprtion retun to liver using LDL receptor
- transfer of CE between lipoproteins is reversible
- without CEPT, LCAT would be inhibited by CE
- inhibition of LCAT would stop efficent removal of cholsterol from circulatin
58
IDL
intermediate density lipoprotein
59
what is the recepto though which HDL delivers cholesterol directly to the liver
SR-B1
60
normal cholestero levels
~5
61
high serum cholesterol is
bad
62
high HDL is
good
63
accumulation of high cholesterol in lymphatic organs and premature CV disease =
Tangier diease
64
what is Tangier disease
accumulation of high cholesterol in lymphatic organs and premature CV disease =
65
what causes Tangier disease
- deficiency of gene coding for ABCA-1 transferase
| - ABC-1 is needed to transport cholesterol out of cells to HDL and enables macrophages to unload cholesterol
66
ABC-1 transferase
ATP binding casette 1
- needed to transport cholesterol out of cells to HDL and enables macrophages to unload cholesterol
- antiatherogenic
67
antiatherogenic
preventing or inhibiting atherogenesis or antiatherogenic effects
68
Apo-1 milano
mutation in Apo A1 that was recognised in a lab in Milan
- Apo A1 is needed to activate LCAT
- carriers have v low HDL so expected to have high incidence of CVD
BUT
people with Apo-1 milano have been shown to live to 100
- presumably from increased efflux of cholesterol
- possible therapeutic treatment?
69
varieties of hyperlipidaemias
- hypercholesterolaemia
- hypertriglycerideaemia
effected by either genetics or diet and lifestyle
70
examples of genetic hyperlipoproteinaemias
- defective LDL receptor
- lipoprotein lipase deficiency
- deficiency of C-11
- deficiency of apoproteins involved in remnant uptake
71
effects of defective LDL receptor
hypercholesterolaemia
| - high LDL in blood
72
effects of lipoprotein lipase deficiency
high chylomicrons and VLDL
73
effects of C-11 deficiency
high chylomicrons and VLDL
74
effects of deficiency of apoproteins involved in remnant uptake
- high chylomicron and VLDL remnant
75
risk factors for secondary hyperlipoproteinaemias
- obesity
- T2D
- dietary cholesterol
- diestry FA (SFA)
- alcoholism
76
how does alcohol effect lipoprotein
- exercise and small amounts of exercise increase HDL but lots of alcohol increases LDL
77
What lifestyle factors increase HDL
exercise and small amounts of exercise
78
difference of dietary FA
- SFA vs PUFA
n-6 PUFA lower cholesterol
n-3 PUFA lower TAG
79
what is lipoprotein a
Lp (a) is LDL with apo-A
80
high levels of Lp(a)
- high concentrations in plasma are associated with increased CHD risk
- levels of Lp(a) are gentic but can be increased by transfat and decreased by oestrogen
- related to plasminogen
- Lp(a) slows the breakdown of blood clots by competeing with plasminogen
81
CHD
coronary heart disease
82
what increases Lp(a)
trans fats
83
what decreases Lp(a)
oestrogen
84
what is atherosclerosis
plaque build up
plaque is:
- complex structure involving inflammation and proliferation of smooth muscle in artery wall
- contains connective tissue and pool of holesterol rich lipid
- stars as a fatty streak from accumulation of foam cells
85
what are foam cells
macrophages filled with lipid, mainly cholesterol
86
how do foam cells effect LDL metabolism
- usually LDL will go to extrahepatic cells when cholesterol is low, and to the liver for excretionwhen cholesterol is high
but, when there's too much LDL it becomes oxidised and is no longer recognised by normal receptor
- oxidised LDL is recognised by scavenger receptor in foam cells
- scavenger regualtors are not down regulated like normal LDL receptors
= cholesterol accumulation
87
what happens to stored fat
hormone sensitive lipase inside adipocyt is activated by glycogen in he fasting state, and inhibited by insulin in the fed state
fasting state:
- free FA are released into bloodstream from adipocytes
- not actually 'free' but they are non-esterified
88
NEFA transport
carried adsorbed to the surface of blood protein: serum albumin
89
why is serum albumin a carrier for many molecules
it has hydrophobic patches on its surface and so is the carrier for many molecules with hydrophobic sections
90
can the brain use FFA as energy source
no, serum bound FFA cannot cross the blood brain barrier
91
ketone bodies function
- act on pancrease to stimulate insulin release
- insulin limits muscle proteolysis and adipose lipolysis
= conservation of muscle tissue
92
ketones action during fasted state
- causes insulin producting from beta cells
- start breaking down fat which limits protein breakdown
- concervse protein, which is the only source of glucose in fasted state
- glucose is needed for brain
93
ketones and diabetes
action of ketones is not good for diabetics
- during starvation, ketons usually causes insulin producting from beta cells
- this cant happen in diabetics
= ketoacidoses from accumulation of ketones = medical emergency
94
What is the mechanism by which malonyl-CoA regulates fatty acid oxidation
inhibits fatty acid transport into mitochondria
