J. Biol. Chem., Vol. 263, Issue 22, 10646-10652, Aug, 1988
Mechanism of formation of the putative advanced glycosylation end product and protein cross-link 2-(2-furoyl)-4(5)-(2-furanyl)-1H- imidazole
FG Njoroge, AA Fernandes and VM Monnier
Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
2-(2-Furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI) is a fluorescent molecule
which was originally discovered in chloroform extract of ammoniacal
solution of acid-hydrolyzed glycated proteins and proposed to represent a
protein cross-link. The absence of a lysyl residue side chain and other
observations promoted a detailed study of its mechanism of formation.
Glycated alpha-t-Butoxycarbonyllysine was incubated for 29 days and
periodically assayed for FFI and FFI-like fluorescence. Whereas
fluorescence increased over time, FFI recovery was unexpectedly highest on
day 0 and lowest on day 29, suggesting that FFI was directly derived from
Amadori products. FFI was also recovered from hydrolysates of glycated
neopentylamine, furosine, and browned poly-L-lysine but was virtually
undetectable in similar solutions basified with NaOH, triethylamine, or
pyridine instead of ammonia. Gas chromatography-mass spectrometry analysis
of FFI from similar hydrolysates basified in the presence of 15N-enriched
NH4Cl revealed for all precursors a parent ion peak at 230 instead of 228
m/e units, suggesting that the two imidazole nitrogen atoms had been
incorporated from free ammonia into FFI. Spontaneous FFI synthesis occurred
when furosine was reacted with aqueous ammonia at room temperature. These
results do not support the proposition that FFI is an advanced
glycosylation end product or a protein cross-link. They suggest that FFI is
formed from ammonia and furosine which are by-products of acid-hydrolyzed
glycated proteins.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
