Lipoproteins and Lipid Transport

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    Lipoproteinsandlipidtransport

    AtifH.Khirelsied,B.Sc,M.Sc,Ph.D.

    Departmentof

    Biochemistry

    FacultyofMedicineandHealthSciences

    InternationalUniversityofAfrica,Khartoum,Sudan

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    Lipoproteinsstructure

    cholesteryl esters)

    Apolipoproteins onthesurface

    large:apoB (b

    48

    and

    B

    100)

    atherogenic

    , ,

    C assi ie ont e asiso ensityan e ectrop oretic

    mobility(VLDL;LDL;HDL)

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    Compositionandphysicalpropertiesofhuman

    li o roteins

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    Lipoproteinsstructure

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    Theapolipoproteins

    Essentialcomponentsoflipoproteins.

    Oftenreferredtoasapoproteins

    Classifiedby

    alphabetical

    designation

    (A

    thru

    E)

    Responsibleforrecognitionofparticlebyreceptors.

    Somehavecatalyticorcoenzymeactivity.

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    Apoproteins ofhumanlipoproteins

    AI(28,300) principalproteininHDL

    90120mg%inplasma;activatesLCAT

    AII(8,700) occursasdimer mainlyinHDL

    30 50mg%;enhanceshepaticlipaseactivity

    B48 (240,000) foundonlyinchylomicron

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    Pro ertiesofthema orclassesofa oli o roteins

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    Electrophorogram ofplasmaproteins

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    Chylomicrons

    Formedinthemucosalcellsintheintestine.

    suclavian veins.

    Degradedto

    remnants

    by

    the

    action

    of

    lipoprotein

    cellsurface

    Remnantsaretakenupbyliverparenchymal cellsdue

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    Dietarycholesterolisabsorbedasesterandtransportedin

    ch lomicrons

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    Thechylomicrons

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    Transferofapoproteins fromHDLtochylomicrons

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    VeryLowDensityLipoprotein(VLDL)

    ascent st en nteractw t togenerate

    mature

    VLDLs

    (with

    added

    cholesterol,

    apoC

    II

    and

    ature

    s

    are

    acte

    upon

    y

    p to

    generate

    VLDLremnants(IDL)

    IDL

    are

    further

    degraded

    by

    hepatic

    triglyceride

    pase togenerate s

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    ThefateofVLDL

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    LDLreceptor

    Receptora soca e B Ereceptor ecauseo itsabilitytorecognizeparticlescontainingbothapos B

    ,

    B100/apo

    E

    binding

    Theintracellulardomainisresponsibleforclustering

    membrane

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    Cholesteroluptakeby

    receptormediated

    endocytosis.

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    HighDensityLipoproteins(HDL)

    Severalsubfamiliesexist

    .

    Itinteractswithchylomicron remnantsand

    lecithincholesterol

    acyl transferase

    (LCAT)

    to

    form

    HDL3

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    ThefunctionofHDL

    Trans ersproteinstoot er ipoproteins

    Picksupcholesterolfromcellmembranes

    ConvertscholesteroltocholesterolestersviatheLCAT

    reaction

    ransportc o estero esterstot e ver re erre toas

    reversecholesteroltrans ort

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    ThefateofHDL

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    Thelecithincholesteryl acyl transferase (LCAT)

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    Thelecithincholesteryl acyl transferase (LCAT)

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    ReversecholesteroltransportbyHDL

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    Thefunctionof CETP

    Thecholesterolestertransfer

    protein(CETP).

    CETPtransferscholesterolesters

    rom o nexc ange

    fortriacylglycerol (TG)

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    Atherosclerosis

    Hardeningofthearteriesduetothedepositionof

    Heartdiseaseistheleadingcauseofdeath

    Causedby

    the

    deposition

    of

    cholesteryl esters

    on

    the

    Atherosclerosis

    is

    correlated

    with

    hi h

    LDL

    and

    low

    HDL

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    Atherosclerosis

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    Factorspromotingelevatedbloodlipids

    age

    men>45yearsofage;women>55yearsofage

    smoking

    h ertension>140 90mmH

    lowHDL

    cholesterol

    obesity>30%overweight

    diabetesmellitus

    inactivity/lackofexercise

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    Optimalanddesirable levelsofserumcholesterolandLDL

    cholesterol

    concentrations

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