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Lipoprotein Study Club 2006

Jun 03, 2018

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Page 1: Lipoprotein Study Club 2006

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Definition

Structure of lipoproteins

Types of lipoproteinFunctions of lipoprotein

Metabolism of lipoproteins

Regulation of lipoprotein metabolism

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 A lipoprotein is a biochemical assembly that

contains both proteins and lipid. The lipids or

their derivatives may be covalently or non-

covalently bound to the proteins. Many

enzymes, transporters, structural proteins,

antigens, adhesins and toxins are lipoproteins.

Examples include the high density and lowdensity lipoproteins of the blood, the

transmembrane proteins of the mitochondrion 

and the chloroplast, and bacterial lipoproteins.

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TriasiglyseridMerupakan bentuk asam lemak cadangan utama

Ester dari alkohol gliserol dengan asam lemak

Unsur utama pembentuk lipoprotein dan cadanganlipid dalam jaringan adiposa

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1. Chylomicrons 

2. Very low density lipoproteins (VLDL)

3. Intermediate density lipoproteins (IDL)4. Low density lipoproteins (LDL)

5. High density lipoproteins (HDL)

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Isolation of Lipoproteins by Ultra-centrifugation

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Composition and Relative Size of Lipoproteins

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• Chylomicrons (derived from diet)

 –  density <<1.006

 – 

 diameter 80 - 500 nm –  dietary triglycerides

 –  apoB-48, apoA-I, apoA-II, apoA-IV, apoCII/

C-III, apoE –  remains at origin in electrophoretic field

-synthesis in gut (intestine)

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 –  density >1.006

 –  diameter 30 - 80nm

 – 

 endogenous triglycerides –  apoB-100, apoE, apoC-II/C-III

 –  prebeta in electrophoresis

 –  formed in the liver as nascent VLDL(contains only triglycerides, apoE and apoB)

-synthesis in liver & gut

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• IDL (intermediate density lipoproteins)

 –  density: 1.006 - 1.019

 – 

 diameter: 25 - 35nm –  cholesteryl esters and triglycerides

 –  apoB-100, apoE, apoC-II/C-III

 –  slow pre-beta-source= VLDL

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 –  density: 1.019 - 1.063

 –  diameter: 18-25nm

 – 

 cholesteryl esters –  apoB-100

 –  beta (electrophoresis)

 –  < 130 LDL cholesterol is desirable, 130-159is borderline high and >160 is high

-Source= VLDL

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 –  density: 1.063-1.210

 –  diameter: 5-12nm

 – 

 cholesteryl esters and phospholipids –  apoA-I, apoA-II, apoC-II/C-III and apoE

 –  alpha (electrophoresis)

-Source = liver,intestine,chylomicrons,VLDL

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Discoidal HDL :

• contains cholesterol,

phospholipid, apoA-I, apoAII,

apoE and is disc shaped;

it is formed in liver and intestine• It interacts with chylomicra

remnants and lecithin-cholesterol

acyl transferase (LCAT) to form

HDL3

HDL3 :

• composed of cholesterol,

cholesterol ester, phospholipid

and apoA and apoE

• interacts with the cell plasmamembranes to remove free

cholesterol

• reaction with LCAT converts HDL3

to HDL2a (an HDL with a high apoE

and cholesterol ester content)• cholesterol ester-rich HDL2a is

then converted to triglyceride-rich

HDL2b by concomitant transfer of

HDL cholesterol esters to VLDL and

VLDL triglycerides to HDL

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• Lipoproteins in the blood, a water medium,

carry fats around the body. The protein particles have charged groups aimed outward so as to attract

water molecules; this makes them soluble in the salt water based bloodpool. Triglyceride-fats and cholesterol are carried internally, shielded by

the protein particle from the water.

The interaction of the proteins forming the surface of the particles with (a)

enzymes in the blood, (b) with each other and (c) with specific proteins on

the surfaces of cells determine whether triglycerides and cholesterol willbe added to or removed from the lipoprotein transport particles.

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Metabolism of lipoprotein

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Bile acids

• cholic acid is the bile acid found in the largestamount in bile

• cholic acid and chenodeoxycholic acid are

referred to as primary bile acids• bile acids are converted to either glycine or

taurine conjugates (in humans the ratio of

glycine to taurine conjugates is 3:1)

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Bile acids

• fat digestion products are absorbed in the first 100cm of small intestine

• the primary and secondary bile acids are reabsorbedalmost exclusively in the ileum returning to the liverby way of the portal circulation (98 to 99%)

• this is known as the enterohepatic circulation

• less than 500 mg a day escapes reabsorption and is

excreted in the feces

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Bile salts

• detergent character of bile salts is due to thehydrophobic-hydrophilic nature of themolecules

• the presence of hydroxyl (or sulfate) and theterminal carboxyl group on the tail gives themolecule its hydrophilic face

the steroid ring with its puckered planeprovides the hydrophobic face

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Function of bile salts

• emulsification of fats due to detergent activity

• aid in the absorption of fat-soluble vitamins

(especially vitamin K)

• accelerate the action of pancreatic lipase

• have choleretic action – stimulate the liver to secrete

bile

stimulate intestinal motility• keep cholesterol in solution (as micelles)

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