CATALYSIS OF REDUCTION OF ALDOS-2-ULOSES (OSONES) BY ALDOSE REDUCTASE- SELECTIVITY FOR THE ALDEHYDIC CARBONYL GROUP

In mammalian tissues, reducing sugars and N-(1-deoxyfructosyl) groups of glycated proteins undergo non-enzymatic reactions to form aldos-2-u loses, or 'osones'. These compounds, which occur in relatively high co ncentrations in diabetic animals, are harmful in that they react with side-chain groups of proteins, adversely affecting their functions. Ho wever, there is evidence for the reduction of aldos-2-uloses in vivo, a process which would be expected to result in a lowering of reactivit y, and serve as a detoxification mechanism. We report that, on incubat ion with aldose reductase and NADPH, o-arabino-hexos-2-ulose (1; 'gluc osone'), 3-deoxy-D-glycero-pentos-2-ulose (2; '3-deoxyxylosone') and 3 -deoxy-D-erythro-hexos-2-ulose (3; '3-deoxyglucosone') gave the corres ponding 2-ketoses, 4, 5, and 6. These results suggest that aldose redu ctase contributes to the conversion of 3 into 6 in vivo, thus accounti ng for the coexistence of both compounds in human blood and urine [K.J . Knecht et al., Arch, Biochem. Biophys., 294 (1992) 130-137]. No aldo ses or alditols were formed in the enzymatic reactions of 1, 2, and 3, indicating that reduction had occurred exclusively at the C-1 (aldehy dic) carbonyl, in contrast to the aldose reductase catalysed reduction of methylglyoxal, which was reported to occur at the C-1 (aldehydic) carbonyl, and, to a small extent, at the C-2 (ketone) carbonyl [D.L, V ander Jagt et al., J. Biol. Chem., 267 (1992) 4364-4369]. The high sel ectivity towards the C-1 carbonyl group is discussed in the light of r ecent information on possible modes of binding of sugars to aldose red uctase. (C) 1996 Elsevier Science Ltd.