lipid transport and dyslipidaemia Flashcards

(45 cards)

1
Q

what are lipids made of

A

cholesterol and triglycerides

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2
Q

what roles do lipids play in the body

A

energy and stores
antioxidants
insulation and protection
hormones

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3
Q

how is fat absorbed from the diet

A
  • Enters as droplets
    • Emulsified by bile salts in intestine
    • Pancreatic lipase breaks down micelles to monoglycerides and free fatty acids
    • Monoglycerides and free fatty acids move into epithelial cells and reform triglycerides
    • Chylomicrons are formed and they are transported into the blood
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4
Q

what are lipoproteins

A

Hydrophobic lipid core and hydrophilic polar phospholipid coating (apoproteins- bind to specific receptors on liver and other tissues)

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5
Q

what are the 5 types of lipoproteins

A

chylomicrons
VLDL - very low density
IDL - intermediate density
LDL- low density
HDL- high density

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6
Q

what are chylomicrons composed of

A

mainly lipids
apoproteins B48, A, C, E

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7
Q

what are VLDLs comprised of

A

mainly triglycerides
apoproteins B100, A, C, E

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8
Q

what are IDLs comprised of

A

50/50 fat and protein
apoproteins B100, E

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9
Q

what are LDLs comprised of

A

cholesterol
apoprotein B100

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10
Q

what are HDLs comprised of

A

protein
apoprotein A1, A11, C, E

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11
Q

what does apoprotein B48 do

A

in chylomicrons, for intestinal uptake of dietary lipids

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12
Q

what does apoprotein E do

A

in chylomicrons, mediates uptake of chylomicron remnants into liver by LDL receptor

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13
Q

what does apoprotein B100 do

A

in VLDL, IDL and LDL, main ligand for LDL receptor

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14
Q

what does apoprotein A1 do

A

in HDL, promotes cholesterol efflux from tissues to liver for excretion

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15
Q

what is the LDL receptor pathway

A
  1. LDL binds on liver hepatocytes
    1. Receptor mediated endocytosis
    2. Taken up into coated vesicles (pH 5)
    3. LDL disassociated from liver
    4. Vesicle pinches to separate receptor and LDL
    5. Vesicle with LDL fuses with lysosome - cholesterol release in cytosol
    6. Vesicle with receptor fuses with cell membrane - replaces LDL receptor
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16
Q

how are exogenous lipids moved around the body

A
  1. absorbed by ileum - moves to lymph, blood to muscle as chylomicrons
  2. TG hydrolysed by lipoprotein lipase to MG and FA
  3. remaining chylomicron remnants with cholesteryl esters endocytosed in liver
  4. cholesterol stores, oxides to bile acids or enters endogenous pathway
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17
Q

how are endogenous lipids moved around the body

A
  1. cholesterol and newly synthesised TG travel to adipose as VLDL
  2. TG hydrolysed by lipoprotein lipase
  3. VLDL is made smaller to LDLs
  4. bind to LDL receptors on cells and deposit cholesterol
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18
Q

what is reverse cholesterol transport

A

HDL removes cholesterol from cells and returns it to the liver

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19
Q

how does reverse cholesterol transport work

A

pre-beta HDL takes cholesterol from cells
LCAT esterifies pre-beta HDL containing cholesterol
transferred by cholesterol ester protein to the liver for excretion

20
Q

what is ACAT

A

acyl CoA - cholesterol acyltransferase
- catalyses intracellular synthesis of cholesteryl ester in macrophages, adrenal cortex, gut and liver

21
Q

what is LCAT

A

lethicin cholesterol acyltransferase
- catalyses cholesteryl ether synthesis in HDL particles

22
Q

what is CETP

A

cholesteryl ester transfer protein
- Transfer of cholesteryl ester between HDL to IDL or VDL

23
Q

what is PLTP

A

phospholipid transfer protein
- Transfer of cholesterol and TG between different classes of lipoprotein particles in plasma

24
Q

what is PCSK9 and how does it affect cholesterol

A
  • Binds to hepatic LDL receptors and promotes their lysosomal degradation
    Prevents recycling of the LDL receptors back onto cell surface of hepatocytes - limits LDL uptake into the liver
25
what is dyslipidaemia
- Disorder of lipid metabolism including lipoprotein overproduction and deficiency Major risk factor for coronary heart disease - directly related to cholesterol levels
26
dyslipidaemia epidemiology
60% adults TC >5mmol/L western diet high in TC/LDL
27
aetiology of dyslipidaemia
primary - 60% secondary - 40%
28
what are the causes of primary dyslipidaemia
genetics - familial hypercholesteremia - familial combined hyperlipidaemia - hype 3 hyperlipidaemia - polygenic hypercholesterolaemia - primary hypertriglyceridemia - lysosomal lipase deficiency dietary and lifestyle
29
what causes secondary dyslipidaemia
- disease - drugs - age - post menopause
30
how are atherosclerosis caused
injury in blood vessel - smoking - DM - high cholesterol - high BP
31
what are the steps in atherosclerosis
- injury in blood vessel - adhesion molecules and monocytes migrate - cholesterol deposited and oxidised - foam cells migrate and stick - plaque formation - necrotic core and fibrous cap formation
32
what are the targets for lipid levels
nothing specific TC <5mmol/L LDL <3mmol/L
33
what is lipoprotein A
LDL species strongly associated with atherosclerosis
34
what 7 classes of drugs can be used for lowering lipid levels
statins fibrates cholesterol absorption inhibitors bile acid binding resins plant stanols/sterols alirocumab inclisiran
35
how do statins work for high lipid levels
competitive reversible HMGCoA reductase inhibitor - decreases cholesterol synthesis
36
how are statins metabolised
CYP450 and glucuronidation
37
how do statins affect the formation of atherosclerosis
increases collagen - plaque stability decreases platelet aggregation anti-oxidant
38
how do fibrates work
PPAR agonists - normally nuclear receptors that modulate lipid and carb metabolism - increase lipoprotein lipase
39
what are cholesterol absorption inhibitors
nicotinic acid and ezetimibe
40
how does nicotinic acid work to reduce cholesterol
water soluble vit B lowers LDL and TG by inhibiting synthesis
41
how does ezetimibe work
inhibits cholesterol absorption in intestine, conjugated to ezetimibe glucuronide and excreted in stools
42
how do bile acid binding resins work
- Bind to cholesterol and excretes it - Can worsen symptoms
43
how do plant stanols and sterols work
decrease cholesterol - dietary and supplements
44
how do alirocumab and evolocumab work
inhibit PCSK9
45
how does inclisiran work
small interfering RNA that inhibits translation of PCSK9 mRNA