A PROFICIENT ENZYME

Orotic acid is decarboxylated with a half-time (t(1/2)) of 78 million years in neutral aqueous solution at room temperature, as indicated by reactions in quartz tubes at elevated temperatures. Spontaneous hydro lysis of phosphodiester bonds, such as those present in the backbone o f DNA, proceeds even more slowly at high temperatures, but the heat of activation is less positive, so that dimethyl phosphate is hydrolyzed with a t(1/2) of 130,000 years in neutral solution at room temperatur e. These values extend the known range of spontaneous rate constants f or reactions that are also susceptible to catalysis by enzymes to more than 14 orders of magnitude. Values of the second-order rate constant k(cat)/K-m for the corresponding enzyme reactions are confined to a r ange of only 600-fold, in contrast. Orotidine 5'-phosphate decarboxyla se, an extremely proficient enzyme, enhances the rate of reaction by a factor of 10(17) and is estimated to bind the altered substrate in th e transition state with a dissociation constant of less than 5 x 10(-2 4) M.