lipoproteins metabolism · 2020. 1. 22. · apolipoproteins (apoproteins) ڇٷ٢ ... activates...

Lipoproteins metabolism الفريق الطبي الأكاديمي

كلــية الطب البشريالمركز/ البلقاء التطبيقية

2016/2022أحياها و من

Done By :- Hanan Jamal and Ahmad Alsahele

Corrected By :- Yousef Marwan

Lipoproteins metabolism و من أحياها

2016/2022

.والمائل هي اضافات بسيطة للتوضيح (الأزرق)كلام الدكتور...(الأسود)السلايدات *

You have to know the types,properties and metabolism of each

one of the lipoproteins and their significance.

Lipids are insoluble in plasma and water. In order to be

transported,they are combined with specific proteins to form

lipoproteins.

In order to circulate in blood they have to be bound to proteins.

Any molecule that is lipid soluble should be bound a protein in

order to to move from one place to another.such as; steroid

hormones,cholesterol and so on.

lipoproteins→ lipids + proteins; their function is to transport

lipids around the body, from liver to adipose tissue to muscle and

so on…

Lipids → cholesterol , phospholipids , TAG.


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Lipoproteins are of five types:

1-Chylomicrons.

2-Very low density lipoprotein (VLDL).

3-Intermediate density lipoprotein(IDL).

4-low density lipoprotein(LDL).

5-High density lipoprotein(HdL)

The differentiation between them is according to their density.

♦The lightest one is chylomicrons <0.95 , and have the highest

concentration of lipids and this because it is the first carrier for

lipids.

♦high density lipoprotein has the highest concentration of proteins.

Lipoprotein’s Density: The higher the lipids the lower the density

The higher the proteins the higher it becomes.


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Four Major Components of Lipoproteins

- Phospholipids

- Cholesterol

- Cholesterol esters

- Triacylglycerols

Cholesterol

Polar

Non polar

Choline

Lecithin

Cholesterol esters and triacylglycerols are inside the lipoprotein

complex ,phospholipids and cholesterol are on the membrane.

Anything polar will be present on the surface of the lipoprotein and

anything non polar would be inside for ex:

The ( OH )part of cholesterol will be at the surface membrane facing

the plasma while the rest of it will be inside the complex.

In comparison to cholesterol esters which has no polar part so it’s

present inside the lipoprotein.


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peripheral

(eg. Apo- C, E)

Integral(eg. Apo- B)

General structure or characteristic of lipoproteins عبارة ع ف انخارج

phospholipids and cholesterol ف

cholesterol ester and triacylglycerol بذاخها جذ

And proteins →

♦ integral proteins (ياخذ كم انغشاء)

♦ peripheral proteins(عهى الأطزاف)

And these proteins we will see that they have different names (types)

such as : apoprotein A , B , C , D , E , E1 ,C2 …

They help lipoproteins circulate in blood.

Simply put they are proteins present on the surface of the lipoprotein

that stabilize the structure of the lipoprotein and have different


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functions according to the type of the apoprotein present on the

lipoprotein.

Separation Methods:

A- Ultra-centrifugation:Using the rate of floatation in

NaCl solution.

Chylomicrons, VLDL, LDL, HDL. and

free fatty acids-albumin

(depending on their density). FFA[carried on albumin.]

B- Electrophoresis:

(Cathode)

Separation of plasma lipoprotein by

electrophoresis on agarose gel

Chylomicrons,

-lipoproteins (LDL ),pre--lipoproteins (VLDL), and

-lipoproteins (HDL). (depending

on the net charge ).

(Anode)

How we can separate lipoproteins? By two methods:

1-Ultra-centrifugation → using centrifuge جاس انطزد انزكشي) ) high

speed and it is possible to reach 10*10^6 gravity we separate lipid

fractions of lipoprotein.

2-Electrophoresis (the most common practice in laboratory) it’s the

only way to know the level of low density lipoproteins.

chylomicrons is the heaviest in weight so it occupies the origin line.

HDL عهى α-lipoproteins

Its the lightest in weight because it contains high percentage of

proteins so it moves the furthest.


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In between are:

LDL عهى β-lipoproteins

VLDL عهى pre-β-lipoproteins

we used electrophoresis previously and considering that

“chylomiccron” is the largest of the lipoproteins and the heaviest it

doesn’t move that much on the electric field and the opposite goes to

HDL the smallest and lightest one of them.

Apolipoproteins(apoproteins)

عبارة ع خس أاع كم احذ يجد عهى ♦ particles of lipoprotein.

They include fivetypes ApolipoproteinA :onHDL and chylomicron)intestine/liver( they are added to the lipoprotein in the intestine and liver

Activates lecithin-cholesterol-acyltransferase )LCAT) and is the ligand for HDL receptor . ApoAII:inhibits LCAT enzyme.

Lcat is responsible for acetilation of cholesterol to give cholesterol

ester.

ApolipoproteinB:

B100:on VLDL and LDLand is ligand for LDL receptor(liver). B$*BB48 48ApoBB48: on chylomicrons(intestine) . ApolipoproteinC:on chylomicrons,HDL and VLDL(Liver)

ApoCI:possible activates LCAT .

Apo A : activates lipoprotein lipase .

ApoCIII: inhibits apoCII.


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ApolipoproteinD: on HDL and may act as lipid transfer protein .

ApolipoproteinE:on chylomicrons,VLDL and HDL and

Is the ligand for lipoprotein remnant and LDL receptors(Liver).

Apolipoproteins carryout several roles: The distribution of apolipoproteins characterizes the lipoprotein

1. Act as structural components of lipoproteins e.g.apoB.

2. Activate enzymes involved in lipoprotein metabolism(enzyme cofactors),

1. ApoA-I for LCAT

2. ApoC-II for lipoprotein lipase

3. Theyact as ligands for interaction with receptors intissues

يعني بيشتغلوا كتعريف♦ )i.e Recogniz ethe cellmembrane surface receptors(.

e.g.apo-B100 and apo–E for LDL receptor and apo-E for the lipoprotein remnant receptor and apoA-I for HDL receptor.


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Lipoproteins lipase بشخغم عهى chylomicrons and TAG عشا طهع يى

fatty acids for muscles and adipose tissue يجد عهى capillary surfaces. Most common phospholipids are phosphatidylcholine & phosphatidylethanol amine


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Source of lipoproteins: 1-Exogenous lipids( رح زح نلأيعاء خقم عهى , انه انهحو انه باكها

(chilomicrons)شكم .extrahepatic tissue بعذا نم

2-Endogenous lipids ( صع داخم انجسى ي انكبذ) VLDL converted to IDL to LDL then goes to the extrahepatic tissues (30%) ,and (70%) returns to the liver.

Extrahepatic tissues بعذ يا حخ ال function of lipids بشا ع طزق

LDL بزجعا يزة ثات نم liver .

بعذا chylomicrons بخخحل نم micells خص ال intestineع فش عا الا

adipose tissue and عهى fatty acids ف انطزق بخسعliverبخزحهمmuscles ,بعذ ال liver بصع lipids(TAG…) بصذرى نم extrahepatic

tissue( LDL and so on…) نا خهصا بزجع HDL بهى lipids بزجعى ل liver , الliver بطهع excess of cholesterol عهى شكم

bile salts (bile acids),

excretory form of cholesterol from bloodاللي همة

Later on someone asked what are micells this is what the de said?

After the lipids are digested for them to be absorbed from the intestine to the

intestinal mucosal cells they move in the for of micells which contains:

Cholesterol, phospholipids, TGA, fat soluble vitamins (and something I

couldn’t hear ) it has all the components of lipids inside the intestine بخجشأ

and protein will be added and become chylomicrons.

Chylomicrons بنضافلهم intestine بدخلوا ال micells يتم امتصاصهم على شكل lipidsال♦

proteins بصيرو chylomicronsهي عبارة عن ا ذا lipid+protein اذا رح

,Colesterol, TAG, phospholipid) بكون فيها lipid% 90يكون فيها cholesterol ester ) يعني فيها كل مكونات الlipoproteins كلهم بكون فيهم نفس

component but with different in concentration اكبرهم , وفيهم بروتين

رح intestine circulatesمن chylomicrons هو rich in fatحجما اللي فيه


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خلال الحركة تبعته بيشتغل thoracic duct في ال lymphatic systemيروح على

رح يروحو للfatty acids وال fatty acid بشيل منه lipoproteins lipaseعليه muscles and adipose tissue for energy production.

glucoseال , glucose for energy production يا بسخخذو فقط ال muscle ال ♦

muscle, liver and heart depend , ال , for short period of time بك فقط

mainly on fatty acids.

They contain mainly TAG, or which of the following has the highest

concentration of the lipid? – chylomicrons

ساعت14عذ فحص داث انذو جب عهى انشخص ا ك صائى نذة

the dr read everything on both figures


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free fatty acid,triglyceride &glycerol كا حج كبز نا شها ي الCMال

صار اصغزBut it’s still rich in TAG triglyceride, CE cholesterol ester, C

cholesterol

Second in size ,rich in TGA.

Metabolic fate of chylomicrons


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لا كا طل انقج سع rich in cholesterlبصزLDL نا خحل انى VLDLال

FA & TAG The role of chylomicrons & VLDL is to transport FA & TAG to other extrahepatic tissues


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LDL is responsible for transport and distribution of cholesterol around the body (rich in cholesterol). LDL transport cholesterol to other tissues for its metabolism. Tissues like muscles, adrenal glands(for cortisol synthesis), gonads(sex hormones), skin(vitamin D) It is produced from the VLDL as we said There are special receptors on cells for LDL


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LDL is the bad cholesterol:- when increased, modified, or oxidized, it is deposited and cause atherosclerosisz

LDL in peripheral tissues perform 3 mechanisms:- 1)cholesterol is stored as cholesterol ester 2) inhibition of cholesterol synthesis(de novo synthesis of cholesterol) by the inhibition of HMG CoA reductase 3)synthesis of cholesterol receptors is inhibited by decreasing transcription process for them. حطبق انخهت ذ انكاشياث بسبب جد فزة ف انكنسخزل عذو انحاجت نهشذ


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So no need for cholesterol synthesis or receptor synthesis and the cell stores cholesterol in the form of cholesterol esters.

Development of atherosclerosis:-

حجع >= حقم يزت انشزا > =blood supply بطئ ف ال>=حصهب انشزا

اسذاد انشزا> =lipidsال


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HDLف كم يكا ال (cholesterol) بانشء انه بسع انشبانتLDLانذكخر شبت ال

(liver)بانشبال انه بجع انشبانت ف يكب انفااث

Cholesterol ester is the storage form of cholesterol


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Nascent HDL means that it has no cholesterol or cholesterol ester.


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Good luck

lipoproteins metabolism · 2020. 1. 22. · apolipoproteins (apoproteins) ڇٷ٢ ... activates...

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