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Connectivetissues

Dr.AtifHassanKhirelsied

DepartmentofBiochemistry

FacultyofMedicineInternationalUniversityofAfrica

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:

1. Structuralproteins:collagenandelastin and

fibrillin1.

2. Specializedproteins:e.g.fibronectin,andlaminin.

3. Proteo l cans.

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Thestructuralproteins

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Elastin confersextensibilit andelasticrecoilintissues.

Elastin ispresentinlargeamountsinlung,largearterial

bloodvessels andsomeelasticli aments.

Smallerquantitiesofelastin arealsofoundinskin,ear

cartila e.

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Unlikecolla en thereisonl one enetict eofelastin.

Itissynthesizedasasolublemonomercalled

.

Tropoelastin isnotsynthesizedinapro formwith

.

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Unlikecollagen,elastin doesnotcontainGlyXY

sequences, r p e e ca s ruc ure,orcar o y ra e

moieties.

Someoftheprolines oftropoelastin arehydroxylated to

h drox roline butthereisnoh drox l sine.

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Similartocollagen,certainlysyl residuesoftropoelastin are

oxidativel deaminated toaldeh des b l s l oxidase.

Themajorcrosslinksformedinelastin arethedesmosine

uni uetoelastin.

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Desmosines crosslink

Desmosines,resultfromthecondensationofthreeofthese

lysinederivedaldehydes withanunmodifiedlysinetoforma

tetra unct ona cross n

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MajorDifferencesBetweenCollagenandElastin

Collagen Elastin

Manydifferentgenetictypes Onegenetictype

conformationspermittingstretching

Gl XY nre eatin structure No Gl XY nre eatin structure

Presenceofhydroxylysine Nohydroxylysine

Carbohydratecontaining Nocarbohydrate

n ramo ecu ar a o cross n s n ramo ecu ar esmos ne cross n s

Presenceofextension Noextension e tides resentdurin

peptidesduringbiosynthesis biosynthesis

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.

tissues(lens,periosteum,aorta).

Issecretedbyfibroblastsandbecomesincorporatedintotheinsolublemicrofibrils.

MutationsareassociatedwithMarfan syndrome.

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Marfansyndrome

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Thespecializedproteins

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Is also found in a soluble form in lasma.

Isinvolvedinmanycellularprocesses,includingtissue

repair,embryogenesis,bloodclotting,andcellmigration/adhesion.

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1. Insoluble l co rotein dimer that serves as a linker

intheECM(extracellularmatrix),producedby

variouscellse.g.,fibroblasts,chondrocytes,

endothelialcells,macrophagesandepithelialcells.

2. Solubledisulphidelinkeddimer foundintheplasma

(plasmaFN),synthesizedbyhepatocytes.

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Fibronectin

Theroleoffibronectins istoattachcellstoavarietyof

extracellularmatrices.

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Fibronectin

Fibronectin containsanArgGlyAsp(RGD)sequencethat

bindstotheintegrin receptors.

TheRGDsequenceissharedbyanumberofother

proteinsintheECMthatbindtointegrins presentincellsurfaces.

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Thelaminins areafamilyofglycoproteins foundinthe

basallamina.

Thelaminins areanimportantforcelldifferentiation,

, .

,

chain,anda chainlinkedtogethertoforman

elon ated cruciform sha e..

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Laminin

integrins oncellsurfaces.

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Theproteoglycans

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Proteoglycansareproteinsthatcontaincovalentlylinked

glycosaminoglycans.

Thebasicproteoglycan unitconsistsofa"coreprotein"

withoneormorecovalentlyattachedglycosaminoglycan(GAG)chain.

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Schematicrepresentationoftheproteoglycan aggrecan.

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Atleast30typeshavebeencharacterizedandgiven

namessuchassyndecan,betaglycan,serglycin,perlecan,aggrecan,vers can, ecor n, g ycan,an romo u n.

Theyvaryintissuedistribution,natureofthecoreprotein,attachedglycosaminoglycans,andfunction.

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Thefunctionof roteo l cans

1. Bin wateran orm y rate matrices.

2. Provideascaffoldforepithelialcellmigration,proliferation,

anddifferentiation.

3. Regulatevariousbiologicalactivitiessuchascoagulation,

hostdefense,andwoundrepair.

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Thefunctionof roteo l cans

4. Bin cyto ines,c emo ines,growt actors,an

morphogens,protectingthemagainstproteolysis.

5. Actasreceptorsforproteasesandproteaseinhibitors

regu a ng e rspa a s r u onan ac v y.

6. Membraneproteoglycanscanactasendocytic receptors

forclearanceofboundligands.

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Glycosaminoglycans

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Glycosaminoglycans

AGAGisanunbranched polysaccharidemadeupof

repeatingdisaccharides.

Onecomponent ofthedisaccharideisalwaysan

aminosu ar,eitherD lucosamineorD

galactosamine.

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Glycosaminoglycans

Theothercomponent(exceptinthecaseofkeratan

su a e sauron c ac ,e er g ucuron c ac

(GlcUA)orits5epimer,Liduronic acid(IdUA).

dGlucuronate liduronate

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Glycosaminoglycans

Thereareatleastseven l cosamino l cans:

1. Hyaluronic acid,

. ,

3. keratan sulfatesI

. era an su a es

5. heparin,

6. heparan sulfate,

7. anddermatan sulfate.

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Glycosaminoglycans (GAGs):

Withtheexceptionofhyaluronic acid,alltheGAGs

containsulfate

groups,

eitherasOestersorasNsulfaten epar nan eparan su a e .

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Thefunctionsofglycosaminoglycans (GAGs):

Hyaluronic acidisespeciallyhighinconcentrationin

embryonictissuesandisthoughttoplayanimportantroleinpermittingcellmigrationduringmorphogenesisand

woundRepair.

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Thefunctionsofglycosaminoglycans (GAGs):

Chondroitin sulfatesarelocatedatsitesofcalcificationin

endochondral boneandincartilage.

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Thefunctionsofglycosaminoglycans (GAGs):

keratan sulfateIand dermatan sulfatearepresentinthe

, .

playaroleinmaintainingtheoverallshapeoftheeye.

Keratan sulfateIisalsopresentincartilage.

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Thefunctionsofglycosaminoglycans (GAGs):

Heparinisanimportantanticoagulant.

ItbindswithfactorsIXandXI,butitsmostimportant

.

Heparincana so in speci ica yto ipoprotein ipase

presentincapillarywalls,causingareleaseofthisenzyme

.

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Thefunctionsofglycosaminoglycans (GAGs):

Heparans havelesssulfategroupsthanheparins

Heparan sulfate areassociatedwiththeplasma

membraneofcells,withtheircoreproteinsspanningthe

membrane.

Theyactasreceptorsandmayalsoparticipateinthe

mediationofcellgrowthandcellcellcommunication.

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Thanks