collagen biochemistry

8/20/2019 Collagen Biochemistry

1/33

Collagen Biochemistry


2/33

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


3/33

Most of us are probably aware thatcollagen is a widely used cosmetic age


4/33


5/33

• Collagen is the most abundantprotein in the animal kingdom


6/33

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


7/33

Collagen is essential for maintaining

tissue integrity


8/33

"hat#s the proof$


9/33


10/33

INTRACELLULAR EVENTS

Collagen biosynthesis


11/33

Collagen hierarchy


12/33

%ntracellular processing


13/33

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/


14/33

)tracellular processing


15/33

)tracellular modi&cations

• N & C-propeptide extensions areremoved

• 0 ( C-procollagen proteinases

• 'educes solubility* enables &brilformation

• +ptimises subse1uent cross-linking


16/33

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


17/33

)tracellular processing %%

Collagen cross-linking


18/33


19/33

3ysyl o)idase initiates cross-link

formation

• Copper containing amine oxidase

• Converts the 4 -amino group of lysineand hydro)ylysine to correspondingaldehydes


20/33

3athyritic agents underpin the criticalimportance of collagen cross-links

• β -aminoproprionitrile


21/33

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


22/33

9yrrole ( 9yridinium Cross-links


23/33

Collagen :bnormalities Congenital*

Metabolic ( :ge-related phenomena


24/33

Congenital +steogenesis imperfecta


25/33


26/33

The biochemical basis of +%


27/33

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


28/33

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.


29/33

0-Carbo)ymethylarginine


30/33

Metabolic bone diseases


31/33

"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


32/33

+steoporosis


33/33

9aget#s Disease

collagen biochemistry

Documents