Polymerization of proteins caused by reaction with sugars and the formation of 3-deoxyglucosone under physiological conditions.

Abstract

Lysozyme,ribonuclease A, ovalbumin and bovine serum albumin were reacted with reducing sugars under physiological conditions of 37°C and pH 7.4, and polymerization of proteins, changes in amino acid composition and carbonyl compounds formed during the reaction were investigated. Incubation of all the protein-sugar systems resulted in noticeable losses of arginine and lysine residues. Polymerization, as well as impairment of arginine residues of lysozyme, with fructose and aldopentose was higher than with aldohexoses. 3-Deoxyglucosone (3DG) was identified as one of the major carbonyl compoundsgenerated in the reaction systems of proteins with glucose and fructose. The formation of 3DGin protein-fructose systems was 1.3~2 times that in proteinglucose systems. Glucose alone did not polymerize succinylated lysozyme, but fructose did and it impaired only arginine residues. These results indicate that 3DGwas generated on the reaction between glucose and free amino groups in proteins, whereas it was generated from fructose alone with the modification of free amino groups. It is strongly suggested that 3DGwas the cross-linker responsible for the polymerization of proteins and the attacker of arginine residues.

In vitro glycation of glomerular basement membrane alters its permeability: a possible mechanism in diabetic complications

“…It is well established that fructose crosslinks proteins more readily than glucose [5,6]. The identities of the cross-links formed are not well understood [7].…”

Immunohistochemical detection of advanced glycosylation end products in diabetic tissues using monoclonal antibody to pyrraline.

“…However, a number of mechanisms may explain why the advanced Maillard reaction as reflected by pyrraline formation may not proceed in all tissue regions at the same rate. First, pyrraline-poor tissue regions may be metabolically more active than others, and enzymes like the 2-oxoreductase have been found to use 3-deoxyglucosone as substrate, thus preventing biochemical consequences of the advanced Maillard reaction such as cross-linking (17,18). Second, the turnover rate ofextracellular matrix poor in pyrraline may be higher due to focal differences in cellular composition.…”

Determination of Urinary Pyrraline by Solid-Phase Extraction and High Performance Liquid Chromatography.

“…[8][9][10][11]20,21) For the HPLC method, a number of procedures have been reported but they had problems that remained to be solved. 15,16) For example, direct infusion of a urine sample to an HPLC equipment, which shortens the life span of the column, requires collection of the pyrraline fraction in the first chromatography and performance of re-chromatography in a second system.…”

“…9) The level of plasma 3-deoxyglucosone, 10,11) an intermediate product in pyrraline and pentosidine formation, has been reported to increase in diabetic 12,13) and in uremic individuals. 14) Recently, chromatographic methods were applied in the measurement of the urinary level of pyrraline, and its increase in diabetic patients was demonstrated, 15,16) suggesting usefulness of the methods for evaluation of diabetic complications.…”