Lipids 3: Lipoproteins Flashcards by Jordan Lyons

How are the structures of micelles and lipoproteins similar and different?

Similar
* both have a hydrophobic core and hydrophilic head forming a spherical droplet
* both have TGs and CEs held within
Different
* The outer layer of the micelle is surrounding by bile acids
* the lipoprotien membrane is made up of phospholipids and has embedded proteins

How well did you know this?

Not at all

Perfectly

Where do chylomicrons first go after leaving the enterocyte cells?

The chylomicrons go into the lymph first where then enter into the peripheral circulation to go to the heart and adipose before going to the liver.

How well did you know this?

Not at all

Perfectly

What is the purpose of the apoproteins on lipoproteins?

The apoproteins serve as a signal for cells to recognize the lipoprotein.
* the apoproteins are made in the enterocyte and packaged with the lipoproteins

How well did you know this?

Not at all

Perfectly

How are lipoproteins classified?

Classified by density such that the more lipids they have the lower the density.
* chylomicrons (least dense)
* VLDL
* IDL
* LDL
* HDL (most dense)

How well did you know this?

Not at all

Perfectly

For chylomicrons what is:
* site of synthesis
* major function
* major apolipoproteins
* residence time in plasma

site of synthesis: intestine
major function: transport dietary lipid to circulation
major apolipoproteins: B48 (also CI, CII, CIII, E)
residence time in plasma: 5-15 min

How well did you know this?

Not at all

Perfectly

For chylomicron remnants what is:
* site of synthesis
* major function
* major apolipoproteins
* residence time in plasma

site of synthesis: conversion by LPL from chylomicrons
major function: transport dietary lipids to liver
major apolipoproteins: B48 and E
residence time in plasma: 15-30 min

How well did you know this?

Not at all

Perfectly

For VLDL what is:
* site of synthesis
* major function
* major apolipoproteins
* residence time in plasma

site of synthesis: liver
major function: transport endogenous cholesterol and TG
major apolipoproteins: B100 (also E, CI, CII, CIII)
residence time in plasma: 15-30 min

How well did you know this?

Not at all

Perfectly

For IDL what is:
* site of synthesis
* major function
* major apolipoproteins
* residence time in plasma

site of synthesis: conversion from VLDL by LPL
major function: intermediate for LDL
major apolipoproteins: B100 (also E)
residence time in plasma: transient

How well did you know this?

Not at all

Perfectly

For LDL what is:
* site of synthesis
* major function
* major apolipoproteins
* residence time in plasma

site of synthesis: conversion from IDL by HL
major function: deliver cholesterol to tissues
major apolipoproteins: B100
residence time in plasma: hours

How well did you know this?

Not at all

Perfectly

For HDL what is:
* site of synthesis
* major function
* major apolipoproteins
* residence time in plasma

site of synthesis: liver and intestine
major function: transport cholesterol to liver
major apolipoproteins: AI (also AII, CI, CIII)
residence time in plasma: hours

How well did you know this?

Not at all

Perfectly

What are the 2 main tissues with census got lipoproteins?

liver and SI

How well did you know this?

Not at all

Perfectly

VLDL/LDL metabolism in the fasting condition

Lipoproteins (B100) are being secreted
* Liver secretes VLDL into circulation and lipoprotein lipase breaks it down into FFAs and glycerol to be used for energy by the muscle.
* The VLDL gets smaller to become IDL which then has hepatic lipase break it down more to LDL
* LDL pretty much just has cholesterol left and goes back to liver to be removed by LDLr

How well did you know this?

Not at all

Perfectly

HDL in the fasting/fed condition

Liver also synthesizes HDL (A1)
* Goes to the periphery and takes cholesterol away from the peripheral cells, so removes it before it builds up too much at those sites and brings back to liver to get rid of it.
* Not really controlled by fed and fasting state but is important for overall cholesterol homeostasis

How well did you know this?

Not at all

Perfectly

Chylomicrons in the fed state

Start eating a meal and have lipids in meal which are digested and packaged in SI with B48 and releases as Chylomicrons which get secreted in lymph and goes to periphery. Can see Chylomicrons with lots of TG and goes to adipose tissue where lipoprotein lipase removes TG and glycerol from here and get taken up by adipose to be stored.
* In fed state lots of calories coming in and dont need that TG for energy so stored until we need it which is typically during fasting.
* Chylomicron remnants left with B48 and some lipids left and this goes to the liver.

How well did you know this?

Not at all

Perfectly

What are Apolipoproteins?

Main protein content of lipoproteins
* KNOW: B48, B100, ApoA1

How well did you know this?

Not at all

Perfectly

Functions of apolipoproteins?

facilitation of lipid transport to receptors
binding of to cell surface receptors, can act as ligands for other interactions in vessel wall
activation of enzymes in lipid metabolism

How do apoliproteins effect the enzyme LPL?

ApoCII activates and ApoCIII inactivates

What is the role of of the enzymes LPL, HTGL, LCAT?

Lipoprotein lipase: hydrolizes TG in chylomicrons and VLDL
hepatic triglyceride lipase: Processes apoE containing lipoproteins such as hydrolyzing TG in HDL and IDL
lecithin cholesterol acyltransferase (LCAT): ApoA1 is cofactor so catalyzes the esterification of HDL cholesterol in cholesteryl esters)

Cholesterol fractions in plasma during fasting

Mostly LDL and HDL

What does the ratio of LDL:HDL indicate?

indicates relative risk of CVD

What is the receptor mediated clearance of lipoproteins?

Removal of LDL via cell receptors
* Liver is the main way → ~90% of lipoproteins are remvoed from plasma by heaptic LDLr
* LDLr is present on many cell types, predominantly hepatocytes, but all cells need cholesterol for membrane synthesis.

What do LDLr regulate?

Levels of LDLr regulate LDL (ligand apo B100) and chylomicron remnant (ligand apo E) removal from plasma.
* This can be manipulated

Describe how to LDLr works?

Receptor-mediated endocytosis for cholesterol homeostasis
* LDLr in plasma membrane so LDL with Apo B48 binds and when it binds, the receptor creates coating and makes vesicle and the whole vesicle gets transported into the cell and the lipo gets taken to a lysosome which breaks down everything but releases the cholesterol which goes to different parts of the cell but mostly the ER and cell gets the supplied cholesterol.

Where does cholesterol synthesis occur?

Takes place in the cytosol close to the ER

How does the body get cholesterol?

Either from lipoproteins or can synthesize it. So when cell needs cholesterol it will take some from plasma via the lipoproteins and will also increase synthesis. * Synthesis is a long process starting off with AcetylCoA and takes a lot of energy to make.

What is the RLS of cholesterol synthesis?

HMG-CoA reductase * HMG-CoA reductase regulated cholesterol very closely to the amount we need. When you have enough cholesterol in cell it will turn off synthesis and reduce the amount coming in from the blood (reducing amount of LDLr on membrane).

What controls HMG-CoA reductase?

HMG CoA reductase is under negative feedback control by mevalonate and cholesterol, which are both products

What drugs inhibit HMG-CoA reductase and why is this important?

Statin class of drugs * Inhibit the HMG-CoA step. Therefore to get cholesterol in cell when needed then need to upregulate the plasma uptake so increases expression of LDLr so more binding partners and end up reducing the amount of LDL plasma.

cellular cholesterol regulation with: * excess cholesterol * low cholesterol * statin therapy | KNOW THIS

* excess cholesterol: Reduce cholesterol synthesis & lower LDL receptor * low cholesterol: Increase cholesterol synthesis & increase LDL receptor * statin therapy: Reduce cholesterol synthesis & increase LDL receptor

How much of cholesterol metabolism is endogenous?

de novo synthesis 800-1500mg/day * Hepatic synthesis: 50%, secreted VLDL * Intestinal synthesis: 30%, secreted chylomicrons

How much of cholesterol metabolism is exogenous?

Animal products in diet 100-300mg/day (dietary intake) * Diet contributes little to total amount of cholesterol, we essentially make what we need?

How might cholesterol metabolism differ between a meat eater and a vegan? | POTENTIAL QUESTION

meat eater might just synthesize less and vegan is unlikely to be in deficit since we synthesize most of it anyways * If you consume excess choelsterol in normal situation, such as meat eater, most normal people will just synthesize less, so decreased HMG-CoA reductase, so you essentially end up at the exact same spot.

What factors can impact cholesterol metabolism homeostasis? | KNOW THIS

Hypercholeresterolemia * increased blood cholesterol (LDL or chylomicrons) which is associated with increased dietary total fat; cholesterol with SFAs increasing risk of developing atherosclerosis * Can also be genetic disorder

What are common risks/causes for dyslipidaemia?

can lead to CVD * genetic * dietary * lifestyle

HDL metabolism

Reverse cholesterol transport * Secreted from the liver and goes to the periphery and takes cholesteryl ester out of the periphery bringing it back to the liver to be secreted into bile as cholesterol or bile acids. * Body cannot break down cholesterol so must be excreted in this way

What happens to the cholesterol once it is secreted into bile?

HDL is taking cholesterol from the periphery (aorta for example) and bringing it to the liver which converts it to bile acids or directly as choelsterol into bile which then goes to the SI and helps to absorb TG and lipids from the diet but absorption back into circulation is not efficient and it is typically excreted into the feces

Summary of lipoprotein metabolism

* Cholesterol can go back to liver to be removed or high concentrations can go into vessel and start accumulating cholesterol so build of the Chylomicrons remnants or VLDL (early stages of CVD) * HDL is much smaller and can go into plaques and remove cholesterol from the plaques and take it away back to the liver.