 In 1972, it was observed that in the dehydration of H2CO3 catalyzed by carbonic anhydrase, the second-order rate constant obtained experimentally was about 1.5 × 1010 M−1 s−1, which was one order of magnitude higher than the upper limit estimated by Alberty, Hammes, and Eigen based on a simplified model.To address such a paradox, Prof. Kuo-Chen Chou and his co-workers proposed a model by taking into account the spatial factor and force field factor between the enzyme and its substrate and found that the upper limit could reach 1010 M−1 s−1, and can be used to explain some surprisingly high reaction rates in molecular biology.The new upper limit found by Chou et al.