CATALYSIS OF REDUCTION OF CARBOHYDRATE 2-OXOALDEHYDES (OSONES) BY MAMMALIAN ALDOSE REDUCTASE AND ALDEHYDE REDUCTASE

In mammalian tissues, carbohydrate 2-oxoaldehydes, or 'osones', formed by cleavage of carbohydrate residues from glycated proteins, cause damage to cells and tissues by cross-linking of proteins. In the substrate specificity study reported here, we show that several osones are relatively good substrates for the reduced, unactivated form of aldose reductase (EC 1.1.1.21) from human and pig muscle, and aldehyde reductase (EC 1.1.1.2) from pig kidney, enzymes that have been well characterised both structurally and mechanistically. Since these enzymes are relatively ubiquitous, they may serve to protect a large number of tissues from damage, by catalysing the reduction of locally-produced osones. Reduction of all substrates by aldehyde reductase obeyed Michaelis-Menten kinetics. In contrast, a Hill constant of about 0.5 was obtained for aldose reductase-catalysed reduction of each of the carbohydrate 2-oxoaldehydes, and for several other substrates that were examined. Although this deviation from Michaelis-Menten kinetics has been ascribed to the presence of two forms of the enzyme, activated and unactivated, our results suggest that it is a characteristic of the unactivated form.