Imperatives for enzymatic catalysis of isomerization of sugars and sugar phosphates

The relative yields of the products of isomerization of D,L-glyceraldehyde in D₂O with intramolecular transfer of a hydride ([1-¹H]DHA) and with proton transfer ([1-²H]DHA) were determined by high-resolution ¹H NMR analyses. A study of the catalysis of this isomerization by deuteroxide ion, buffer anions and Zn²⁺ established the following: (1) isomerization with proton and hydride transfer occurs at approximately equal rates in dilute solutions of sodium deuteroxide; (2) Brønsted bases catalyze isomerization with proton transfer in a bimolecular reaction; (3) Zn²⁺ catalyzes isomerization with hydride transfer in a bimolecular reaction; and (4) Zn²⁺ and acetate ion react in concert to catalyze isomerization with proton transfer in a termolecular reaction. These results show that the various pathways for isomerization with proton and hydride transfer proceed via transition states of similar energies, so that there is no strong imperative for enzymatic catalysis by any particular reaction mechanism. The relevance of these results to the mechanism of action of xylose isomerase is discussed briefly.