Lecture 14--plasma lipoproteins Flashcards by Isabella Gillett

3 classes of lipids…

(1) Cholesterol(Chol)
(2) Triglycerides(TGs)
(3) Phospholipids (PLs)

How well did you know this?

Not at all

Perfectly

Functions of cholesterol

(1) structural role

2) Precursor (bile salts, steroid hormones, vit D

How well did you know this?

Not at all

Perfectly

Functions of TGs

(1) Energy transport/storage
(2) Thermoregulatory (insulation)
(3) Protection of organs

How well did you know this?

Not at all

Perfectly

Functions of Phospholipids

(1) Membranes
(2) Lipid transport
(3) Nerves
(4) Cell signalling (surface coating of lipoproteins)

How well did you know this?

Not at all

Perfectly

Normal plasma [cholesterol]
LDL chol: \_\_\_
HDL chol: \_\_\_
LDL/HDL ratio: \_\_\_
Total chol: \_\_\_

LDL chol: 1 mmol/L

LDL/HDL ratio:

How well did you know this?

Not at all

Perfectly

(Normal plasma concentration)

LDL chol: ____mmol/L

How well did you know this?

Not at all

Perfectly

(Normal plasma concentration)

HDL chol: ____mmol/L

> 1 mmol/L

How well did you know this?

Not at all

Perfectly

(Normal plasma concentration)

Total chol: ____mmol/L

How well did you know this?

Not at all

Perfectly

(Normal plasma concentration)

LDL/HDL ratio: ____

How well did you know this?

Not at all

Perfectly

(Normal plasma concentration)

Triglycerides: ____mmol/L

How well did you know this?

Not at all

Perfectly

Forms of cholesterol

(1) FREE cholesterol

2) Cholesterol esters (storage form) (chol + FA

How well did you know this?

Not at all

Perfectly

What’s the composition of lipoproteins (LPs)

Central core: TGs & Chol esters

Outer surface coat: Phospholipids, apoproteins, free cholesterol (structural function)

How well did you know this?

Not at all

Perfectly

What are LIPOPROTEINS

Transport lipids from site of absorption/synthesis to peripheral tissues

How well did you know this?

Not at all

Perfectly

what are the 6 classes of lipoproteins

(1) Chylomicrons (CM)
(2) CM remnants
(3) VLDL (v. low density)
(4) IDL (Intermediate density)
(5) LDL (low density)
(6) HDL (high density)

How well did you know this?

Not at all

Perfectly

What are the main apoproteins found on each class of lipoprotein?

**CM–> ApoB-48

*VLDL–> ApoB-100
*LDL–> ApoB-100 (only apoprotein on LDL)

**ApoCII –> on ALL BUT LDL (i.e. ApoCII–>CM/VLDL/HDL/IDL)

How well did you know this?

Not at all

Perfectly

Which LPs have the most TG %?

CM and VLDL
CM=90%
VLDL =~60%

How well did you know this?

Not at all

Perfectly

In fasted state the dominant TG store is contained in which LP? why?

In fasted state VLDL = predominant TG store

Because the short 1/2 life of CM (5-30 minutes) means it is not present in the blood of a fasted individual.

How well did you know this?

Not at all

Perfectly

Which LPs have the >best esterified cholesterol content?

LDL = 60% esterified cholesterol

Why does the density of lipoproteins shift from lowest in CM–>CMremnant–>VLDL–>IDL–>LDL (highest in LDL)?

To do with change in composition of LP.
The outer surface coating is made of higher density components than the TG/chol ester core so when the TGs are hydrolysed(and removed from the LP) the outer surface coating makes up a higher fraction of the LP and therefore the density increases.

Order the LP classes in order of density (1=most dense, 5=least dense)

HDL
LDL
IDL
VLDL
CM

Order the LP classes by diameter (1=largest diameter, 5=smallest)

CM
VLDL
IDL
LDL
HDL

Differentiate CM & VLDL formation (synthesis & secretion)

**CM–> synthesised in enterocytes, released into the lymphatic circulation (as too large to diffuse directly into blood)

**VLDL–> synthesised in liver, released directly into circulation

What’s bad cholesterol? Why?

LDL = bad cholesterol

1) Oxidised readily
2) Taken up by macrophages in arterial walls
3) => Accumulate cholesterol esters = formation of foam cells
4) Atherosclerosis (=>coronary heart disease)

A ___% increase in [LDL] –> ____% ___ in CHD risk

10% increase in [LDL]

–> 20% increase in CHD risk

What is the 1/2 life of a chylomicron?

5-30 minutes

What is the 1/2 life of VLDL?

12 hours

What is the 1/2 life of LDL?

1-3 days

What is the 1/2 life of HDL?

5-6 days

What apoprotein is expressed on chylomicrons?

Apo-B48

What is the function of apoproteins

(1) MAINTENANCE of LP STRUCTURE (structure/strength) (2) Regulate LP METABOLISM (cell uptake/metabolism depends on the type of apoprotein) (3) COFACTOR for enzymes of lipid metabolism

On what lipoproteins is Apo-B100 expressed and what is its function?

Expressed on VLDL & LDL is a LIGAND FOR LDL RECEPTORS

On what LP is Apo-B48 expressed?

Expressed on CM & CM remnants -receptor binding domain is absent (truncated/missing)

On what LP is Apo-CII expressed and what is its function?

Expressed on HDL/CM/VLDL/IDL (all but LDL) Essential cofactor required for hydrolysis of lipoproteins by lipoprotein lipase (interacts with lipoprotein lipase in capillary beds leading to TG hydrolysis)

Outline CM formation

1. (Intestinal lumen) Fat emulsified, MICELLES --> absorbed to enterocytes 2. (ER) FORMATION OF LIPOPROTEINS ==>Involves enzymes ...ACAT (esterifies cholesterol) ==>MTP (microsomal transfer protein, essential for CM formation in enterocytes...packages together the CM) 3. Released into the LYMPHATIC CIRCULATION

What is the function of ACAT

Esterifies cholesterol (involved in formation of Chylomicrons)

What is the function of MTP

Microsomal transfer protein Essential for CM formation in enterocytes Packages Chylomicrons

What is the EXOGENOUS PATHWAY for lipid metabolism

Pathway involving CHYLOMICRONS (1) Absorbed (Micelles) (2) Chylomicrons (3) Released to lymphatics (4) TGs (in CM) are hydrolysed as they pass through capillary beds & Free FAs are released (Either for energy or storage as lipid droplets in adipocytes) (5) Left with the CHYLOMICRON REMNANT which is TAKEN UP BY THE LIVER & removed from the circulation

What is the ENDOGENOUS PATHWAY for lipid metabolism?

(1) Liver => VLDL (released to circulation) (2) VLDL => IDL + FFA (hydrolysis of TGs when pass over capillaries) (3) IDL => 1/2 removed from circulation at liver, other 1/2 is metabolised again (IDL=> LDL + FFA) (4) LDL => Taken up by peripheral tissues (can easily be oxidised and taken up by macrophages leading to formation of foam cells (=atherosclerosis = CHD)

What's REVERSE CHOLESTEROL TRANSPORT?

HDL-->circulation-->removes lipids/chol from peripheral tissue/macrophages/foam cells -->returns them to the liver to be recycled/disposed of

What is the role of LIPOPROTEIN LIPASE in lipid metabolism?

- -Present in ADIPOSE TISSUE, MAMMARY GLAND, HEART, MUSCLE - ApoCII = essential cofactor (apoprotein on all LPs except LDL) - hydrolyses TG as pass over capillary beds in Lipoproteins

LDL receptor pathway

Delivery of cholesterol from LDL --> Peripheral tissues ``` LDL receptors ApoB100 ligands Binds Particle internalised Lysosome breaks down LP particle Receptor = recycled ```

What are the consequences of increasing [chol] in peripheral tissues?

(1) REDUCES Cholesterol SYNTHESIS (reduces expression of HMG-CoA REDUCTASE) (2) INCREASES STORAGE of cholesterol esters in cells (increases synthesis of ACAT (esterifies free cholesterol with FAs) (3) REDUCES LDL RECEPTOR expression (=reduces LDL uptake)

ACAT

Esterifies free cholesterol with FA for storage

What are the pathways for lipid metabolism?

(1) ENDOGENOUS (VLDL-Liver) (2) EXOGENOUS (CM-Intestine) (3) REVERSE CHOL TRANSPORT (HDL-Liver)