Recent Progress in Understanding the Mechanism of Formate Dehydrogenases

Recent work concerning the reaction mechanism of the molybdenum‐containing formate dehydrogenases is discussed, focusing on two alternate mechanisms of action for the enzyme involving either formation of CO 2 or bicarbonate as the immediate product of the reaction. On the basis of the pH dependence of the rate of reduction of enzyme by formate and the results of a recent GC/MS study undertaken under single‐turnover conditions indicating that no 18 O from solvent H 2 18 O is incorporated into product CO 2 , it is concluded that bicarbonate cannot be formed in the course of the reaction, and that cysteine, once dissociated from the molybdenum, cannot be functioning as a base in the course of the reaction.