1,2-Dicarbonyl sugars such as 3-deoxy-D-erythro-hexos-2-ulose (3-deoxy-D-glucosone, 1  ) and D-arabino-hexos-2-ulose (D-glucosone, 2  ) have been implicated in the degradation of D-glucose in vivo, with 1  commonly detected as a metabolite in diabetic patients.  The contiguous electrophilic carbonyls in 1  and 2  make them susceptible to nucleophilic attack by protein side-chains (e.g., arginine), leading to structural modification and in some cases loss of protein function.  Recent studies of the solution behavior of 1  using 13C NMR and 13C/2H-labeled compounds showed that 1  rearranges in aqueous phosphate buffer at pH 7.5 and 37 �C to give metasaccharinic acids via an intramolecular 1,2-hydrogen transfer mechanism.  Under the same solution conditions, the degradation of 2  has now been investigated by 13C and 1H NMR spectroscopy with the use of singly and doubly 13C labeled isotopomers.  Unlike 1  , 2   initially undergoes C1-C2 bond cleavage to yield D-ribulose 3  and formate.  Monitoring the fates of the sketetal carbons during the conversion of 2  to 3  also revealed that this C1-C2 bond cleavage is accompanied by C1-C2 transposition in about 1 out of every 10 transformations.  Furthermore, the degradation of 2  is catalyzed by inorganic phosphate (Pi), and the Pi surrogate, arsenate, and may involve an osone-phosphate (or osone-arsenate) adduct as an intermediate.   These findings suggest a new role for Pi in the degradation of 1,2-dicarbonyl compounds in vivo.  This work was supported by the National Institute of Diabetes and Digestive and Kidney Disease, research grant No. DK065138.

Degradation of the 1,2-dicarbonyl sugar, D-glucosone,  is Pi-catalyzed and accompanied by C1-C2 transposition

243rd National Meeting (2012)

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