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8/20/2019 Collagen Biochemistry
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Collagen Biochemistry
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This lecture will cover
• Collagen as a vital connective tissueprotein
• Distribution of collagen in nature
• The key collagen types
• Collagen biosynthesis
•
Collagen cross-linking andstabilisation
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Most of us are probably aware thatcollagen is a widely used cosmetic age
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• Collagen is the most abundantprotein in the animal kingdom
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6. Ma!or collagen types
http://image.slidesharecdn.com/collagen-biochemistry-1193520978345960-5/95/collagen-biochemistry-6-728.jpg?cb=1193495779http://image.slidesharecdn.com/collagen-biochemistry-1193520978345960-5/95/collagen-biochemistry-6-728.jpg?cb=1193495779
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Collagen is essential for maintaining
tissue integrity
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"hat#s the proof$
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INTRACELLULAR EVENTS
Collagen biosynthesis
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Collagen hierarchy
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%ntracellular processing
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Collagen undergoes post-
translational modi&cation
• Lysine and proline hydroxylation
• 'esult from lysyl ( prolyl hydro)ylaseaction* ferrous iron* o)ygen ( ascorbate
• 'esidues provide stability
• %n case of +,-lysine* they serve asglycosylation sites and cross-linking sites
•
OH-lysine glycosylation• lucosyl ( galactosyl transferases
• May aid in collagen shipment to C/
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)tracellular processing
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)tracellular modi&cations
• N & C-propeptide extensions areremoved
• 0 ( C-procollagen proteinases
• 'educes solubility* enables &brilformation
• +ptimises subse1uent cross-linking
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hlers Danlos
• ,ighly elastic skin %n rare cases it canbe fragile Chronic !oint pain* !ointla)ity /coliosis %ncreased risk of bone
fracture 2ragile blood vessels Mitralvalve prolapse
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)tracellular processing %%
Collagen cross-linking
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3ysyl o)idase initiates cross-link
formation
• Copper containing amine oxidase
• Converts the 4 -amino group of lysineand hydro)ylysine to correspondingaldehydes
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3athyritic agents underpin the criticalimportance of collagen cross-links
• β -aminoproprionitrile
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The cross-links of bone ( dentine
collagen
• The lysyl and hydroxylysyl aldehydesreact with adacent ! -amino "ro#pso$ other lysine%hydroxylysine
resid#es & 'ET(A)INES• Bivalent cross-links* 5st phase cross-links
• etoamines converted to trivalent or 7 ndphase cross-links by reaction with anotherlysyl8hydro)ylysyl aldehyde
• *yrrole + pyridini#m cross-lin,s
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9yrrole ( 9yridinium Cross-links
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Collagen :bnormalities Congenital*
Metabolic ( :ge-related phenomena
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Congenital +steogenesis imperfecta
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The biochemical basis of +%
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Metabolic ( :ge-related alterations
to collagen
• hy is colla"en .#lnera/le0 – long lived protein
– /usceptible to modi&cation
– Turnover8renewal and function of tissuesare compromised
• 1ia/etes will res#lt in colla"en
chan"es
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Diabetes ( collagenchanges
• lycation ; modi&ed amino acids
– ; e.g.* pentosidine* 0-carbo)ymethylarginine
• 3ipid pero)idation
• Malondialdehyde* product of 2:o)idation* also reacts with somecollagen cross-links
•Collectively they alter the materialproperties andproteolytic susceptibility.
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0-Carbo)ymethylarginine
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Metabolic bone diseases
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"hat are the changes$
• 2one colla"en acc#m#lation
• Raised /one colla"en t#rno.er – @ery large increases in 9%C9
– 3arge increases in catabolic enAymes
– ,ypomineralised collagen
• Cartila"e splittin"3 cartila"e loss
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+steoporosis
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9aget#s Disease