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year 3 exam 1 > lipid transport and dyslipidaemia > Flashcards

lipid transport and dyslipidaemia Flashcards

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
Q

what is dyslipidaemia

A
  • Disorder of lipid metabolism including lipoprotein overproduction and deficiency
    Major risk factor for coronary heart disease - directly related to cholesterol levels
26
Q

dyslipidaemia epidemiology

A

60% adults TC >5mmol/L
western diet high in TC/LDL

27
Q

aetiology of dyslipidaemia

A

primary - 60%
secondary - 40%

28
Q

what are the causes of primary dyslipidaemia

A

genetics
- familial hypercholesteremia
- familial combined hyperlipidaemia
- hype 3 hyperlipidaemia
- polygenic hypercholesterolaemia
- primary hypertriglyceridemia
- lysosomal lipase deficiency
dietary and lifestyle

29
Q

what causes secondary dyslipidaemia

A
  • disease
  • drugs
  • age
  • post menopause
30
Q

how are atherosclerosis caused

A

injury in blood vessel
- smoking
- DM
- high cholesterol
- high BP

31
Q

what are the steps in atherosclerosis

A
  • 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
Q

what are the targets for lipid levels

A

nothing specific
TC <5mmol/L
LDL <3mmol/L

33
Q

what is lipoprotein A

A

LDL species strongly associated with atherosclerosis

34
Q

what 7 classes of drugs can be used for lowering lipid levels

A

statins
fibrates
cholesterol absorption inhibitors
bile acid binding resins
plant stanols/sterols
alirocumab
inclisiran

35
Q

how do statins work for high lipid levels

A

competitive reversible HMGCoA reductase inhibitor - decreases cholesterol synthesis

36
Q

how are statins metabolised

A

CYP450 and glucuronidation

37
Q

how do statins affect the formation of atherosclerosis

A

increases collagen - plaque stability
decreases platelet aggregation
anti-oxidant

38
Q

how do fibrates work

A

PPAR agonists - normally nuclear receptors that modulate lipid and carb metabolism
- increase lipoprotein lipase

39
Q

what are cholesterol absorption inhibitors

A

nicotinic acid and ezetimibe

40
Q

how does nicotinic acid work to reduce cholesterol

A

water soluble vit B
lowers LDL and TG by inhibiting synthesis

41
Q

how does ezetimibe work

A

inhibits cholesterol absorption in intestine, conjugated to ezetimibe glucuronide and excreted in stools

42
Q

how do bile acid binding resins work

A
  • Bind to cholesterol and excretes it
  • Can worsen symptoms
43
Q

how do plant stanols and sterols work

A

decrease cholesterol - dietary and supplements

44
Q

how do alirocumab and evolocumab work

A

inhibit PCSK9

45
Q

how does inclisiran work

A

small interfering RNA that inhibits translation of PCSK9 mRNA

year 3 exam 1 (44 decks)

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