Production and Metabolism of 3-Deoxyglucosone in Humans

Abstract

3-deoxyglucosone (3DG), a reactive dicarbonyl sugar involved in nonenzymatic glycation of proteins is found in elevated concentrations in diabetic patients and has been implicated in the pathogenesis of diabetic complications. In this study, we provide ex-vivo and in-vivo evidence for production of 3DG via the fructose-3-phosphokinase pathway. Evidence of further metabolism of this carbohydrate by oxidative and reductive pathways to 2-keto-3-deoxygluconate (DGA) and 3-deoxyfructose (3DF), respectively, is presented. Levels of these three sugars, 3DG, DGA and 3DF, in blood components and fluids from normoglycemic and diabetic humans are summarized. A comparison of the relative levels of 3DG and 3DF in urine from normoglycemics and diabetics suggests a possible impairment of the detoxification of 3DG to 3DF in diabetics.