Scheme 1.

Proposed course of the catalytic reaction of UGDH. For clarity reasons, only the herein relevant amino acids of the active site of hUGDH are shown. The concerted mechanism would be inconsistent with exchange of the proton at glucosyl C-5 with solvent. The stepwise mechanism might allow proton exchange due to accumulation of enzyme-bound UDP-gluco-hexodialdose. Unless UDP-gluco-hexodialdose was released from the active site (which probably does not happen as shown later), exchange reaction would have to take place at the active site of the enzyme.