title: Inhibitory effects of pyridoxal phosphate, ascorbate and aminoguanidine on nonenzymatic glycosylation.
abstract: Nonenzymatic glycosylation of serum albumin was studied in the presence of naturally occurring metabolites, pyridoxal, pyridoxal phosphate and ascorbate/dehydroascorbate, and a hydrazine compound, aminoguanidine. Pyridoxal, pyridoxal phosphate, ascorbate and dehydroascorbate, at concentrations of 0.1 mM or greater, significantly inhibited the nonenzymatic glycosylation of albumin. Aminoguanidine was the most potent inhibitor of nonenzymatic glycosylation and 54% or 85% inhibition occurred when 5 or 50 mM aminoguanidine, respectively, was present in the incubation mixture containing 20 mM glucose. A major effect of aminoguanidine was to lower the free glucose concentration in the incubation mixture by a direct reaction with glucose as judged by thin layer chromatography. The present studies suggest that vital metabolites such as pyridoxal phosphate and ascorbate may be potentially important in controlling glucose-induced nonenzymatic glycosylation of proteins. Pyridoxal phosphate forms a Schiff base with proteins as does glucose and therefore may be a preferable drug, over aminoguanidine which is a hydrazine, for inhibiting the effects of glucose-induced nonenzymatic glycosylation.
authors.affiliation: Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University of Pennsylvania, Philadelphia 19104.
authors.forename: M
authors.initials: M
authors.lastname: Khatami
authors.forename: Z
authors.initials: Z
authors.lastname: Suldan
authors.forename: I
authors.initials: I
authors.lastname: David
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: J H
authors.initials: JH
authors.lastname: Rockey
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology*; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology*; D007700:Kinetics; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism*
chemical_list: D006146:Guanidines; D012710:Serum Albumin, Bovine; D011732:Pyridoxal Phosphate; D001205:Ascorbic Acid; C004479:pimagedine