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Connectivetissues
Dr.AtifHassanKhirelsied DepartmentofBiochemistry FacultyofMedicine InternationalUniversityofAfrica

Collagen
AtifHassanKhirelsied
B.Sc.,M.Sc.,Ph.D.,Biochemistry.

FacultyofMedicine InternationalUniversityofAfrica

Collagen
Collagenisthemajorinsolublefibrousproteininthe extracellularmatrixandinconnectivetissue.

Collagen
Isresponsibleforskinelasticity,anditsdegradationleads towrinklesthataccompanyaging.

Themostabundantproteininmammals,morethan25% p , ofbodyproteins.

Fillsoutthecornea whereitispresentincrystallineform.

Hasgreattensile strength,inligaments andtendons.

Isalsousedincosmetic surgery,forexamplelip enhancement.

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Collagen
Thereareatleast16typesofcollagen,90%percentof thecollageninthebodyconsistsoftypesI,II,andIII

Collagen
Type RepresentativeTissues Fibrillar collagens I Skin,tendon,bone,ligaments,dentin,interstitial tissues II Cartilage,vitreoushumor III Skin,muscle,bloodvessels V SimilartotypeI;alsocellcultures,fetaltissues Similar to type I; also cell cultures, fetal tissues Fibrilassociatedcollagens VI Mostinterstitialtissues IX Cartilage,vitreoushumor;

Themostabundanttypesofcollagen

Sheetformingcollagens IV Allbasallaminaes

Collagenstructure

CollagenComponents
Insolubleglycoprotein (protein+carbohydrate)

Protein highglycine andtwomodifiedaminoacidshydroxylysine, hydroxyproline (glyXY)n. Carbohydrate (glucose,galactose)

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Collagenstructure

CollagenStructure
Collagenisafibrousproteinbuiltupof

Collagenhasanunusual aminoacidcomposition.

threecalledchains(nothelices)which formaropelike triplehelix.

Collagenhasanunusualaminoacid composition,everychainconsistsofa repeatingtriplet(GlyXY).

ECM:Extracellularmatrix.

CollagenStructure

CollagenStructure
Theglycine issmallenoughtofitintothecenterofthe triplehelix.

Inadditiontotheglycine collagencontains(proline, In addition to the glycine collagen contains (proline hydroxyproline andhydroxylysine).

Theselateraminoacidsresultsfromposttranslational Primary,secondary,andquaternarystructuresofcollagen. modification.

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CollagenStructure

Proline isfoundintheXpositionand4hydroxyproline in theYposition.

Thehydrogenbonding stabilizesthetriplehelix.
Interchain hydrogenbondingincollagen.The amidehydrogenof aglycine residueinonechainishydrogenbondedtothecarbonyl oxygenofaresidue,oftenproline,inanadjacentchain.

Collagensynthesis

Covalentcrosslinksincollagen.(a)Anallysine residuecondenseswith alysineresiduetoformanintermolecularSchiffbasecrosslink.(b)Two allysine residuescondensetoformanintramolecular crosslink.

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Orderandlocationofeventsincollagensynthesis

Typesofcollagen
Type I collagen is the most common fibrillar collagen (90%), and is found in bone, skin, tendons, vascular, ligature, organs,. Type II collagen provides similar tensile strength to cartilage. Collagen Type III - reticular fibers with type I. Type IV and VII collagens are network-forming collagens; they form a meshwork, particularly in basal lamina.

Typesofcollagen
Collagen Diseases - Excess
Other types of collagen do not form fibers, e.g., type IX collagen (and type XII) are fibril-associated collagens, which link type I (or type II) collagen fibrils together. They are more flexible than fibrillar collagens because the GXYrepeats of their -chains are interrupted more frequently by other amino acids. 1. Fibrosis. 2. Lung- pulmonary fibrosis. 3. Overproduction 3 O erprod ction of collagen I I. 4. Liver- over consumption of alcohol. 5. Arteries- atherosclerosis.

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CollagenDiseases Insufficient
1. Scurvy 2. Ehlers-Danlos syndrome ( y (rubber-man) ) 3. Osteogenesis imperfecta 4. Atopic dermatitis (AD)

Collagen Diseases Insufficient Scurvy 1. Dietary vitamin C deficiency 2. Needed for hydroxylation of proline and lysine. 3. Form too few hydrogen bonds in collagen. 4. Skin, bone, teeth weakness and malformation . 5. Blood vessels weakened, bleeding.

Scurvy symptoms
1. malaiseandlethargyandbonepain 2. skinchangeswithroughness,easy bruisingandpetechiae. b ii d t hi 3. gumdisease,looseningofteeth, 4. poorwoundhealing,andemotional changes.

Scurvy

Swolleninflamedgumsinscurvy

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CollagenDiseases Insufficient
Ehlers-Danlos syndrome (rubber-man)

CollagenDiseases Insufficient
Osteogenesis imperfecta

1. Skin and tendons easily stretched

1. Brittle-bone syndrome 2. Mutation in Type I procollagen 3. Fail to assemble triple helix 4. Degrade imperfect collagen 5. Leads to fragile bones

characterizedby; 1. loosejoints. 2. Elasticskin,""Indiarubberskin

Osteogenesis Imperfecta
Also known as Brittle Bone Disease, or "Lobstein syndrome

Is characterized by abnormal bone formation in babies