Duan > Lipowhatthefuckever Flashcards by Rhonda Mittenzwei | Brainscape

Q

what are lipoproteins?

A

protein-lipid complexes responsible for transport of plasma lipids

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Q

what is on the surface of a lipoprotein?

A

phospholipids (duh)
unesterified cholesterol
apolipoproteins

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Q

what is in the core of a lipoprotein?

A

cholesterol esters

triglycerides

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Q

what are the 3 lipids?

A

triacylglycerol
phospholipids
cholesterol & cholesterol esters

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Q

what is the difference btwn triacylglycerol & phosopholipid?

A

triacylglycerol has 3 FAs w/ a glycerol backbone, phospholipids only have 2 FAs

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Q

where is Apo A-I?

A

liver & small intestine

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Q

what does Apo A-I do?

A

structural

activate LCAT

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Q

where is Apo A-II?

A

liver

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Q

what does Apo A-II do?

A

strucutral
inhibit hepatic lipase
component of ligand for HDL binding

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Q

where is Apo A-IV?

A

small intestine

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Q

what does Apo A-IV do?

A

activate LCAT

modulate LPL

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Q

where is Apo A-V?

A

liver

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Q

what does Apo A-V do?

A

direct fxnal role unk

regulates TG levels

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Q

where is Apo B-100?

A

liver

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Q

what does Apo B-100 do?

A

structural
synthesize VLDL
ligand for LDL-Receptor

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Q

what does Apo B-48 do?

A

structural

make chylomicrons

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Q

where is Apo B-48?

A

small intestine

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Q

what is Apo B-48 from?

A

from apo B-100 mRNA after specific mRNA editing

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Q

where is apo C-I?

A

liver

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Q

what does apo c-I do?

A

activate LCAT

inhibit hepatic TGRL uptake

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Q

what does apo C-II do?

A

activate LPL

inhibit hepatic TGRL uptake

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Q

where is apo C-II?

A

liver

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Q

where is apo C-III?

A

liver

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Q

what does Apo C-III do?

A

inhibit LPL

inhibit hepatic TGRL uptake

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Q

where is apo E?

A

liver
macrophages
brain

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Q

what does apo E do?

A

ligand for apoE receptor

mobilize cellular cholesterol

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Q

which lipoproteins are in the liver?

A

A-I
A-II
A-V
B-100
C-I
C-II
C-III
E

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Q

which lipoproteins are in the small intestine?

A

A-I
A-IV
B-48

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Q

which lipoproteins are in macrophages & the brain?

A

ONLY E!

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Q

what is the smallest lipoprotein?

A

HDL

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Q

how big is HDL?

A

9-15 nm

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Q

how big is LDL?

A

20-22 nm

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Q

how big are chylomicrons, VLDL, and their catabolic remnants?

A

> 30 nm

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Q

what are the biggest lipoproteins?

A

chylomicrons, VLDL, and their catabolic remnants

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Q

what is the density of HDL?

A

1.063-1.21 g/mL

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Q

what is the density of LDL?

A

1.019-1.063 g/mL

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Q

what is the density of chylomicrons, VLDL, & their catabolic remnants?

A

<1.006 g/mL

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Q

what affects the diameter & density of lipoproteins?

A

CE/TG/phospholipid/lipoprotein composition

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Q

what is the % total lipid & % total protein content of HDL?

A

50%

50%

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Q

what is the % total lipid & % total protein content of LDL?

A

80% total lipid

20% total protein

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Q

what is the % total lipid & % total protein content of IDL?

A

85% total lipid

15% total protein

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Q

what is the % total lipid & % total protein content of VLDL?

A

92% total lipid

8% total protein

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Q

what is the % total lipid & % total protein content of chylomicrons?

A

99% total lipid

1% total protein

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Q

what 3 things make up total lipid content?

A

CE
TG
phospholipids

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Q

what is the general trend as density of a particle decreases with total lipid and total protein?

A

lower density = larger diameter
higher lipid content
lower protein content

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Q

what are the 2 pathways for lipoprotein metabolism?

A

exogenous/chylomicron pathway

endogenous/VLDL pathway

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Q

what pathway does dietary fat use for lipoprotein metabolism?

A

exogenous/chylomicron

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Q

what happens to lipids synthesized by the liver (what lipoprotein metabolism pathway)?

A

endogenous/VLDL pathway

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Q

what are the 5 steps of the exogenous/chylomicrons pathway?

A

bile salts solubilize dietary TG
pancreatic lipases hydrolyze TGs
diffuse into intestinal epithelial cells
ER re-synthesizes TG
packaged into chylomicrons

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Q

what is the half life of a chylomicron?

A

5-30 min

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Q

which apolipoproteins are in chylomicrons initially?

A

apo A

apo B-48

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Q

which apolipoproteins on chylomicrons are acquired in circulation?

A

apo E

apo Cs

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Q

what activates LPL?

A

apo C-II

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Q

where is LPL primarily?

A

on surface of capillaries of adipose & muscle tissue

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Q

what does LPL do?

A

hydrolyze TG to free FA + glycerol

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Q

what % of a chylomicron is TG?

A

> 90%

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Q

what % of a chylomicron is CE + cholesterol?

A

<5%

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Q

what % of a chylomicron is phospholipids?

A

5-10%

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Q

what % of a chylomicron is protein?

A

1-2%

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Q

what happens to the free FA from a chylomicron?

A

can be reused for energy or re-esterified

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Q

what happens to chylomicrons as they lose TG?

A

they shrink

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Q

what do apo E and apo C get transferred to (from a chylomicron)?

A

HDL

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Q

what is a chylomicron called when all the apo C is gone?

A

chylomicron remnants

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Q

what is the composition of a chylomicron remnant?

A

CE > TG

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Q

what happens to LPL after the chylomicron loses apo C-II?

A

no longer activated

Q

what happens to chylomicron remnants?

A

taken up by liver

Q

what is the half-life of a chylomicron remnant?

A

~5 min

Q

what is the function of a chylomicron?

A

transport dietary lipids from the intestines to adipose, skeletal, & cardiac muscle tissue

Q

where does a chylomicron get apo C II and apo E?

A

from HDL

Q

what apolipoproteins does a chylomicron remnant have?

A

apo E

apo B-48

Q

what is VLDL responsible for?

A

endogenous TG formation & transport

Q

are VLDLs bigger or smaller than chylomicrons?

A

smaller

Q

what is the surface monolayer of VLDL composed of?

A

12% phospholipids
14% free cholesterol
4% protein

Q

what is the hydrophobic core of VLDL composed of?

A

65% TG
8% CE
C 8-10%, CE 12-15%
idk man this is weird

Q

what lipoproteins does VLDL have?

A

apo Cs (C-II from HDL)
apo E
apo B-100

Q

what is the half-life of VLDL?

A

~12 hours

Q

what are TGs hydrolyzed by?

A

LPL

Q

VLDLs decrease in size to become what?

A

IDL

Q

what happens if you lose Apo C-II?

A

less activation of LPL

Q

what is the composition of IDL?

A

TG about the same as CE

Q

what lipoproteins are on IDL?

A

apo Cs
Apo E
Apo B-100

Q

what is the half-life of IDL?

A

minutes to an hour

Q

what takes up 50% of IDLs?

A

the liver

via apoE & Apo B-100

Q

what happens to the IDLs that do not get taken up by the liver?

A

loses TG

becomes LDL

Q

what is the primary carrier of cholesterol in the blood?

A

LDL

Q

what lipoprotein has the highest cholesterol?

A

LDL

Q

what is the composition of LDL?

A

5% TG
20% protein
70% C + CE

Q

what removes LDL?

A

LDLR via apo B-100

Q

what is the half life of LDL?

A

2.5-3 days

Q

what lipoproteins have apo B-100?

A

VLDL, IDL, LDL

Q

increased apo B-100 is correlated w/ what?

A

increased CVS disease

Q

what is the genetic defect assoc w/ familial defective apo B?

A

glutamine substituted arginine at amino acid 3500 > missense mutation

Q

what is familial defective apo B?

A

affects binding affinity of apo B-100 at its receptor (i.e. the LDL receptor)

Q

where can you find the LDL receptor?

A

hepatic & extrahepatic tissues

Q

what happens when an LDL particle binds to the receptor?

A

the receptor-LDL complex is endocytosed

Q

what happens to the cholesterol in LDL after the LDL-receptor complex is endocytosed?

A

cholesterol is de-esterified & released as free cholesterol in cytoplasm > can be used in membranes

Q

what re-esterifies XS cholesterol?

A

ACAT

acyl-CoA-cholesterol acyl transferase

Q

what pathway occurs in the small intestine?

A

exogenous pathway

Q

what pathway occurs in the liver?

A

endogenous pathway

Q

what does ACAT do in the intestine/exogenous pathway?

A

regulates dietary cholesterol absorption

Q

what does ACAT do in the liver/endogenous pathway?

A

esterifies cholesterol for production & release of VLDL

Q

what does ACAT promote?

A

foam cell formation & atherogenesis

Q

what does LDL come from?

A

VLDL

+ LPL

Q

where is HDL synthesized?

A

liver & small intestine

Q

what does HDL do?

A

transports cholesterol from peripheral tissues to liver

Q

what is the composition of HDL?

A

CE & phospholipids (50/50)

Q

what lipoproteins are present in HDL?

A

apo A-I
apo A-II
apo C-II
apo E

Q

what is the cofactor for LCAT?

A

apo A-I

Q

what is LCAT?

A

lecithin cholesterol acyl trasnferase

Q

what does LCAT do?

A

esterifies cholesterol > moves into interior of particle to enlarge HDL

Q

what happens to HDL particles as the circulate through the bloodstream?

A

they acquire cholesterol & phospholipids and grow

Q

what does CETP do?

A

exchange VLDL TGs against HDL CEs

Q

what are the 2 mechanisms of cholesterol regulation?

A

rate of cholesterol synthesis

2. rate of LDL receptor transcription

Q

what are the 4 primary lipoprotein disorders?

A

primary chylomicronemia
familial hypertriglyceridemia
familial combined hyperlipoproteinemia
familial dysbetalipoproteinemia

Q

what is primary chylomicronemia?

A

LPL or cofactor deficiency

increased chylomicrons & VLDL

Q

what is the result of hypertriglyceridemia?

A

increased VLDL

+/- chylomicrons

Q

what is the result of familial combined hyperlipoproteinemia?

A

increased VLDL
OR
increased LDL
OR
both

Q

what is the result of familial dysbetalipoproteinemia?

A

increased VLDL remnants & chylomicron remnants

Q

what do mutations in the LDL receptor lead to?

A

familial hypercholesterolemia

Q

what do most LDL receptor mutations result in?

A

impaired fxn

Q

what do SOME LDL receptor mutations result in?

A

fewer receptors d/t impaired cell processing

Q

what is the clinical result of heterozygous LDL receptor mutation?

A

serum cholesterol up to 2x normal

~5% have MI before 60yo

Q

what is the clinical result of homozygous LDL receptor mutaiton?

A

high serum cholesterol
CVD signs at an early age
MI by 20yo

Q

are hetero or homozygous mutations in the LDL receptor more common?

A

heterozygous (1 in 500)

homo is 1 in 1 million

Q

what happens to TGs in alcoholism?

A

increase

Q

what happens to TGs in liver disease?

A

increase

Q

what happens to VLDL & chylomicrons in alcoholism & liver disease?

A

VLDL is low to normal

chylomicrons increase

Q

T/F: only type 1 diabetes increases risk for CVD

A

FALSE

type 1 & 2

Q

how does insulin affect LPL transcription?

A

increases it
increased removal of TGs
decreased VLDL

Q

what happens to LPL transcription if insulin is low or if pt is insulin resistant?

A

decrease in LPL transcription

Q

what happens to VLDL if insulin is low or if pt is insulin resistant?

A

increase VLDL

less effect of chylomicrons

Q

what happens to proteins & lipids with high blood sugar?

A

can become glycated

increased risk of atherogenesis

Q

what are the LDL mods in atherosclerosis?

A

oxidation of apo B-100

glycation

Q

HDL has at least 2 antioxidant enzymes that can inhibit or reverse WHAT?

A

oxidation

Q

what is a scavenger receptor?

A

binds to modified LDL (in atherosclerosis) & endocytosed the particles

Q

what are foam cells?

A

cholesterol accumulates in macrophages > XS is deposited as droplets in cytoplasm

Q

how does LDL impact atherosclerosis?

A

LDL moves out of arterial lumen & into arterial wall > modified & oxidized > inflammation > foam cells

Q

what is the first step for therapy for atherogenic heart disease?

A

lowering plasma LDL thru diet & meds

Q

how do statins work (GENERALLY)?

A

block cholesterol production

increase expression of LDL receptor by liver

Q

what is another name for the statins?

A

HMG-CoA reductase inhibitors

Q

what are the 6 statins you need to know?

A

lovastatin
simvastatin
pravastatin
fluvastatin
atorvastatin
rosuvastatin

Q

what are the 4 mechanisms of action of the statins?

A

inhibits HMG-CoA reductase
decrease in cholesterol synthesis
increased synthesis of hepatic LDL receptors
increased LDL uptake

Q

how do statins impact TG, LDL, & HDL?

A

= or dec TG
dec LDL
= or inc HDL

Q

what are the clinical uses of statins?

A

lowering LDL
heterozygous familial hypercholesterolemia
secondary hypercholesterolemia d/t diabetes

Q

what can you combine statins w/ to achieve greater effects & 50% reduction in LDL?

A

bile acid-binding resins
or
ezetimibe

Q

when does the majority of cholesterol synthesis occur?

A

at NIGHT

Q

when are statins most effective (what time of day)?

A

at NIGHT bc that’s when cholesterol synthesis occurs

Q

what are 2 other possible uses for statins?

A

osteoporosis

anti-inflammatory (modulate immune system AND decrease high sensitivity CRP)

Q

what are the side effects of statins?

A

HA
photosensitivity
MYALGIA & MYOPATHY (grapefruit!)
rarely liver damage

Q

how are statins cleared?

A

P450A (CYP3A4)

Q

what can statins interact w/?

A

GRAPEFRUIT JUICE
dihydropyridine CCBs
St. John's wort
fibrates
niacin
ketoconazole
erythromycin

Q

what is a possible consequence of statin therapy w/ other drugs?

A

increase levels of oral contraceptives, digoxin, & warfarin

Q

what are the bile acid-binding resins?

A

cholestyramine
colestipol
colesevelam

Q

what is the mechanism of action of bile acid binding resins?

A

anion exchange resin

binds bile acids in intestine > increased fecal excretion of bile acid

Q

how do bile acid binding resins get absorbed?

A

they DON’T!

they’re hydrophobic & unaffected by digestive enzymes so they remain unchanged

Q

what are the results of bile acid binding resins?

A

increased pdtion of LDL receptors

increased activity of HMG-CoA reductase

Q

how are TGs, LDL, and HDL affected by bile acid binding resins?

A

inc or dec TGs
decreased LDL
= HDL

Q

when do you use bile acid binding resins?

A

pts w/ high LDL

Q

what do bile acid binding resins have an ADDITIVE effect in lowering LDL w/?

A

nicotinic acid & statins

Q

what are the side effects of bile acid binding resins?

A

GI probs, nausea, indigestion
steatorrhea in high dose
impaired absorption of vitamins (A, D, E, K, folic acid)
may cause hyperchloremic acidosis