Mechanistic imperatives for aldose-ketose isomerization in water: Specific, general base- and metal ion-catalyzed isomerization of glyceraldehyde with proton and hydride transfer

The deuterium enrichment of dihydroxyacetone obtained from the aldose-ketos e isomerization of D,L-glyceraldehyde in D2O at 25 degreesC was determined by H-1 NMR spectroscopy from the integrated areas of the signals for the al pha -CH2 and alpha -CHD groups of the product. One mole equivalent of deute rium is incorporated into the product when the isomerization is carried out in 150 mM pyrophosphate buffer at pD 8.4, but only 0.6 mol equiv of deuter ium is incorporated into the product of isomerization in the presence of 0. 01 M deuterioxide ion, so that 40% of the latter isomerization reaction pro ceeds by the intramolecular transfer of hydride ion. Several pathways were identified for catalysis of the isomerization of glyceraldehyde to give dih ydroxyacetone. The isomerization with hydride transfer is strongly catalyze d by added Zn2+. Deprotonation of glyceraldehyde is rate-determining for is omerization with proton transfer, and this proton-transfer reaction is cata lyzed by Bronsted bases. Proton transfer also occurs by a termolecular path way with catalysis by the combined action of Bronsted bases and Zn2+. These results show that there is no Large advantage to the spontaneous isomeriza tion of glyceraldehyde in alkaline solution with either proton or hydride t ransfer, and that effective catalytic pathways exist to stabilize the trans ition states for both of these reactions in water. The existence of separat e enzymes that catalyze the isomerization of sugars with hydride transfer a nd the isomerization of sugar phosphates with proton transfer is proposed t o be a consequence of the lack of any large advantage to reaction by either of these pathways for the corresponding nonenzymatic isomerization in wate r.