Lipoprotein Metabolism: Part 1 Flashcards by Dylan Hall

What is the structure of lipoproteins?

They are micelle like structure with a hydrophobic core

Made of proteins and phospholipids

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What does the hydrophobic core of lipoproteins contain?

Fat and cholesterol mainly

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What is the purpose of lipoproteins?

Since triglycerides and cholesterol are lipophilic substances, they are packaged by the liver and intestine as part of a water soluble carrier (the lipoprotein)

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What is the purpose of chylomicrons?

Class of lipoprotein

They deliver dietary lipids to liver from the gut

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What is the purpose of VLDL?

class of lipoproteins 
Very low density 
Deliver endogenous lipid to tissue

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What is the purpose of LDL?

Class of lipoproteins
Low density lipoprotein
deliver cholesterol to cells

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What is the purpose of HDL?

Class of lioproteins
High density lipoprotein
Reverse cholesterol transport

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What are apoproteins and their function?

“apo” describes the protein within the shell of the particle in its lipid-free form

They activate certain enzymes required for normal lipoprotein metabolism
Act as ligands on the surface of lipoproteins that target specific receptors on tissues that require lioprotein delivery for their innate cellular function

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What is Apo A1?

Apoproteins

Produced by: liver, intestine

Expressed by: HDL

Function: Activates LCAT for cholesterol trapping in HDL, marker of HDL

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What is Apo B48?

Apoprotein

Produced by: intestine

Expressed by: Chylomicron

Function: Assembly and secretion of chylomicrons from small intestine, marker of chylomicron

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What is apo B100?

Apoprotein

Produced by: Liver

Expressed by: LDL, VLDL, IDL

Function: ligand of LDLR for LDL

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What is Apo CII?

Apoprotein

Produced by: Liver

Expressed by: chylomicron, VLDL, IDL, HDL

Function: activator of lipoprotein lipase (LpL)

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What is Apo CIII?

apoprotein

Produced by: Liver

Expressed by: Chylomicron, VLDL, IDL, HDL

Function: Natural inhibitor of LpL, and hepatic lipase, blocks hepatic absorption of lipoproteins

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What is Apo E?

Apoprotein

Produced by: liver

Expressed by: Chylomicron, VLDL, IDL, HDL

Function: Ligand of LDLR for chylomicron, VLDL, IDL, HDL

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What is the purpose of lipoprotein lipase (LpL)?

Main enzyme that cleaves fatty acids of TG from travelling lipoproteins.

Must be activated by apoCII which is present in the lipoproteins

Its transported to the nearest endothelial lining of capillaries

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What is the role of apo-CII in terms if LpL?

It binds LpL to activate, it occurs in the nearest capillaries of needy adipose tissue, cardiac muscle and skeletal muscle

What is Hormone sensitive lipase (HSL)?

Similar to LpL, its inhibited by insulin and activated by epi and cortisol

Stress and other conditions increase circulating fatty acid

What is Low-density lipoprotein receptor (LDLR)?

All lipoproteins require LDLR for interaction for endocytosis (fusion) to the tissue

What are the two ligands of LDLR?

ApoE and ApoB100

What is the primary pathway from removal of cholesterol from circulation?

Since all lipoproteins use LDLR, its the primary (70%) pathway fro removal of cholesterol

What is PCSK9?

Have to do with recycling of LDLR in the liver

Secreted protease that binds to and promotes degradation of the LDLR protein

What is ApoC-III?

Have to do with recycling of LDLR in the liver
it inhibits the binding of lipoproteins to the LDLR

*a mutation in the apoC-III gene results lower cholesterol and triglycerides and less incident of AMI

What is the least dense of the lipoproteins?

The chylomicrons because of their rich triacylglcerol content

What do chylomicrons do with dietary triglycerides and cholesterol?

They collect it and bring them back to the liver via the bloodstream

What are the major apoproteins of chylomicrons?

ApoB-48 (marker) It also carries Apo CII, the apoCII activates LpL, in the capillaries of adipose tissue, cardiac muscle and skeletal muscle **This activation allows LpL to hydrolyze the chylomicrons, which leads to release of fatty acids from triacylglycerides ***liver cells bind to chylomicron remnants thro ApoE, allowing them to receptor-mediated endocytosis

What is the purpose of very-low-density lipoproteins (VLDL)?

In the liver, excess fatty acids are converted into triacylglycerols, dietary fat along with free and esterified cholesterol, and packaged which forms VLDL

What are intermediate-density lipoprotein (IDL)?

half of the VLDL are not taken up by the liver, but have additional core triacylglycerol removed to form IDL **can not differentiate IDL and VLDL since they have the same apopprotein markers

What is Low-density lipoproteins (LDL)

Generated from IDL Rich in cholesterol and cholesterol esters Most of it is reabsorbed by the liver * *LDL has no apoproteins expect apoB100 * ***High levels of circulating LDL is the major cause of CVD

Where is HDL created?

Its created by the liver and intestine as small HDL (nascent)

What is the major benefit of HDL?

Its their ability to remove cholesterol from cholesterol-laden cells and to return the cholesterol to the liver This helps in vascular tissue since cholesterol makes the walls harder **the increase in the cholesterol level blocks HMG CoA reductase activity in the liver, it lowers LDL production

What is familial hypercholesterolemia (FH)

Severe hypercholesterolemia whith cholesterol deposits in tendons and premature heart disease **effects genes in LDL receptor (60%) and apolipoprotein apoB100 (30%) ***this leads to a high number of LDL remaining in circulation leading to CVD

What leads to the high level of cholesterol in a person (high LDL)?

Is not due to over production of cholesterol by the liver or overeating cholesterol rich foods - its due to poor reabsorption of LDL by the liver

How does atherosclerotic plaque build up?

1. Poor reabsorption of LDL by liver leads to more in plasma 2. These (specially smaller LDLs) enter the sub-endothelial space (intima) 3. These are oxidized which lead to inflammation which recruits more circulating monocytes 4. this is what dmgs the cell

How do you calculate LDL?

total cholesterol -{HDL + (triglycerides/5)} Example: lipid panel of a person is TC= 220, HDL = 35, TG = 200. what is LDL 220 - {35+(200/5)} 145

Why do you need to have a 12 hour fast before measuring triglyceride and cholesterol levels?

Because if you eat it can increase the level of those by 20-30%