Enzymatic Reversibility of Nonenzymatic Glucosylation?

Donald M. Kirschenbaum, Department of Biochemistry, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203 (USA) Dear Sir, The chemistry of the glycosylation of proteins, the reaction between proteins and carbohydrate, is shown below, H H I I H-C=0 H-C=N-Pr H-C-N-Pr I I I (H-C-OH)4+H2N-Pr – –► (H-C-OH)4 – –* C=0 ! ← I ← I CH2OH CH2OH (H-C-OH)3 CH2OHI II III (Pr= Protein) The article ‘Enzymatic Reversibility of Nonenzymatic Glycosylation of the Glomerular Basement Membrane’ [1] contains some errors in basic chemistry. Lubecet al. [1, p. 26] write: ‘The basic reaction involves the formation of an aldimine, the formation of a ketoamine undergoing the Amadori rearrangement ...’. It is the aldimine (II) which undergoes the Amadori rearrangement producing the ketoamine (III). They then go on and write: ‘This N-glycosidic linkage ...’ (p. 27). In the ketoamine (III) the carbohydrate portion is linked via a-C3⁄8-group to the nitrogen atom of the protein. Therefore the product of the Amadori rearrangement, the ketoamine (III), is an N-alkylated compound and not a glycoside and there is no glycosidic linkage. The removal of the carbohydrate moiety attached to the nitrogen atom, which their extract does, might be due to an oxidative reaction finally producing an aldehyde. The reaction is essentially an oxidative dealkylation of nitrogen and has its analogues in N-demethylases. 1 Faculty Exchange Scholar-SUNY. It is also possible that the enzyme complex in the extract is reversing the Amadori reaction producing an aldimine (II) which is hydrolyzed to the starting materials glucose (I) and protein. When the fate of the nitrogen-containing groups on the protein to which the carbohydrate had been bound are known then, and only then, can the enzyme removing the carbohydrate be named. It is premature to call the enzyme a hydrolase. Lubec et al. [1] also report that no fructose, only glucose (1) was found on examination of the hydrolysates. It is possible that the reversibility of ketoamine formation [2] goes through an intermediate in which the asymmetry of C-2 is destroyed. No fructose would be found but