ADVANCED NUTRITION: LIPOPROTEINS

Lipoproteins

Transporting hydrophobic compounds (lipids) in an aqueous environment (blood)

Cholesterol esters and triglycerides along with some integral apoproteins

What is the core of lipoproteins mainly composed of?

Can be sent to extrahepatic tissues as fatty acids

Glycerols

Remnants

HDL

How are plasma chylomicrons cleared?

Lipoprotein lipase

capillary endothelial cells of heart, muscle and adipose – not in liver

Becomes Cholesterol and Fatty acid

What happens to the chylomicron remnants in the liver?

LRP and ApoB100 E receptors

The two types of receptors that chylomicrons remnants can go under?

Nascent Chylomicron

When dietary TG enters the small intestine, what comes into the bloodstream?

apoCII

activates LPL (speeds chylo/VLDL clearance)

apoCIII & Angiopoietin-like 4 (ANGPTL4)

inhibits LPL (slows chylo/VLDL clearance)

has lower Km (= higher affinity) for TG and oxidizes

In LPL regulation, what is unique about muscle

– has higher Km (= lower affinity) for TG

– Upregulated by insulin

In LPL regulation, what is unique about adipose

ApoE

hepatic uptake of chylomicron remnants and LDL clearance

ApoE3

allele most common (60% E3/E3; 35% heterozygous E3)

E2/E2

(Arg158 → Cys) have elevated blood lipids (TG, cholesterol), atherosclerosis. (E2 allele frequency 7%) because of poor binding of E2 to the hepatic remnant receptor

E4/ E4

Cys112 → Arg) is also associated with atherosclerosis, and with Alzheimer’s disease (not causative for AD). (E4 allele frequency 14%)

VLDL

Precursor particles contain PL shell with Apo B-100 and a core of CE

• TG is added via MTP (microsomal TG transfer protein)

• If TG content in ER is low, then ApoB100 is degraded

• TG cleared by LPL, similar to CM clearance

• ~90 mins half-life

Apo B-100

PL shell and a core of CE

MTP (microsomal TG transfer protein)

Have TF added to this

ApoB100

If TG content in ER is low, then what is degraded?

Lomitapide

treatment of hyperlipidemia acts as an inhibitor for MTP

Fatty Acids in lipoprotein lipases

Glycerol

IDL (VLDL remnant)

HDL broken down by Apo C

How are VLDLs cleared? (seperate into?)

LDL receptor and LRP

Two transporters of VLDL?

ApoC

Broken down VLDL to HDL

ApoA and ApoC

Broken down Chylomicron to HDL

LDL and Liver

Where can VLDL remnants and IDL go to?

lipoprotein lipase)

TG hydrolysis by LPL rom VLDL → IDL

endothelial lipase & hepatic TG lipase

TG hydrolysis by HTGL from IDL → LDL

LCAT & CETP

in plasma and bound to HDL → activated by ApoAI on HDL with Exchange of TG from VLDL and IDL for CE from HDL

ACAT

adds a FA onto cholesterol to produce CE

High-density lipoprotein- HDL

Picks up free cholesterol from liver,

macrophages, intestine – removes cytotoxic free

cholesterol from cells – reverse cholesterol transport

(can also be the reverse). Contributes apoCII and apoE to TG-rich

lipoproteins (i.e. CMs and VLDL and IDL) Smallest of the lipoproteins

• Highest density (high ratio of protein:lipid)

ApoAl

What is the main Apoprotein of HDL?

no

Is LDL the same as LDL-C?

Apo B100

Apo B-48

Apo E

Apo A-I

Apo AII

Apo C-I

Apo- CII

Apo C-III

5 minutes

How long does it take for chylomicrons to be cleared?

90 min

How long does it take for VLDLs to be cleared?

15 hrs

How long did it take for LDL to be cleared?

Conversion of HDL2 to pre beta HDL

1st step of HDL cycle?

Pre beta-HDL

Lipid poor Apo A-1

Pre beta-HDL enters in the capillary endothelium to spread to the peripheral cells and converts to Discodial HDL and pass by lymph

2nd step of the HDL cycle

When Discoidal HDL is converted to HDL3 by LCAT

3rd step to The HDL cycle

CETP and cholesterol ester converts HDL2 to VLDL (CETP rxn)

4th step of the HDL cycle