Screening for glucose-triggered modifications of glutathione.
Nonenzymatic protein glycation is caused by a Schiff's base reaction between the aldehyde groups of reducing sugars and the primary amines of proteins. These structures may undergo further Amadori rearrangement and free radical-mediated oxidation to finally generate irreversible advanced glycation end products (AGEs). One of the factors known to modulate the glycation of proteins is glutathione, the most abundant nonprotein thiol tripeptide with the gamma-linkage, H-Glu(Cys-Gly-OH)-OH (GSH). Screening for products formed by GSH with D-glucose is an essential step in understanding the participation of GSH in glycation (the Maillard) reaction. Under the conditions used in these studies we observed N-(1-deoxy-D-fructos-1-yl)-pyroglutamic acid as the major glycation product formed in the mixtures of GSH and glucose in vitro. A RP HPLC/MS and tandem MS analyses of the GSH/glucose mixtures revealed that cleavage of the N-terminal glutamic acid and the formation of pyroglutamic acid-related Amadori product were accompanied by generation of Cys-Gly-derived Amadori and thiazolidine compounds.
Jerić
Ivanka
I
Division of Organic Chemistry and Biochemistry, Rud er Bosković Institute, Zagreb 10002-HR, Croatia.
Horvat
Stefica
S
D002851:Chromatography, High Pressure Liquid; D005947:Glucose / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D015394:Molecular Structure; D053719:Tandem Mass Spectrometry; D053778:Thiazolidines / Q000737:chemistry
D053778:Thiazolidines; D005978:Glutathione; D005947:Glucose