Healthcare and Medicine Reference
In-Depth Information
attentions to a detailed analysis of nonfluorescent components associated with
highly cross-linked collagen and identified a nonfluorescent component,
nonfibrillar collagen-1 (NFC-1), the presence of which could be correlated to
a change in physiochemical properties consistent with increased cross-linking.
The concentration of NFC-1 present in tissue (NFC-1/collagen molecule) and
its increase with age suggested that it could be an important intermolecular
cross-link. More recent evidence has shown that NFC-1 is a complex consisting
of imidazolones derived from GO and methyl glyoxal reacting with arginine
and an as yet uncharacterized high-molecular-weight component; the latter is
believed to be the cross-link moiety (748).
Glycation has in fact been shown to interfere with cell-matrix and collagen-
matrix interactions. For example, glycation of basement membrane alters its
binding characteristics with heparin and laminin (749), and fibronectin (750)
and glycation of the cell binding domain of type IV decreased endothelial
adhesion and spreading (746). Similarly, platelet aggregation and adhesion to
collagen are known to be dependent on the quaternary structure of the col-
lagen (751) and involve specific domains in the molecule. The modification of
arginine residues in collagen by carbonyl compounds results in the formation
of the respective imidazolones (748). GO reacts to form either No-(4-oxo
-5-dihydroimidazol-2-yl)-L-ornithine (748) or 1-(4-amino-4-carboxybutyl)-2-
imino-5-oxo-imidazolidine (752), whereas MG forms a 4-imidazolon-2-yl
derivative existing in three tautomeric forms (748, 753) (Figs. 1.32 and 1.33).
An intensive treatment reduced the skin collagen glycation in type 1 diabetes
HO
OH
H 3 C
OH
O
O
CH 3
O
OH
N
CH 3
NH
NH
NH
HN +
HN +
HN +
N
HN
NH
NH
NH
O
O
O
H 2 N
H 2 N
H 2 N
O
H 2 N
HO
OH
OH
OH
Glyoxal-
arginine
Methylglyoxal-
arginine
3-Deoxyglucosone-
arginine
Argpyrimidine
(2 methylglyoxal +
arginine)
Imidazolones
FIG. 1.32 Structures of different imidazolones resulting from the modification of
arginine residues by different carbonyl compounds (first three structures) and the reac-
tion product of arginine with two molecules of MG (argpyrimidine, right structure)
(according to Bailey et al., Mech. Ageing Dev. 106: 1-56, 1998).
Search Pocayo ::




Custom Search