Diffusion-limited enzyme

Since the rate of catalysis of such enzymes is set by the diffusion-controlled reaction, it therefore represents an intrinsic, physical constraint on evolution (a maximum peak height in the fitness landscape).

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,[5] which was one order of magnitude higher than the upper limit estimated by Alberty, Hammes, and Eigen based on a simplified model.

[3][4] To address such a paradox, 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,[6][7][8] and can be used to explain some surprisingly high reaction rates in molecular biology.

[5][9][10] The new upper limit found by Chou et al. for enzyme-substrate reaction was further discussed and analyzed by a series of follow-up studies.

If the proton tunneling theory remained a controversial idea,[15][16] it has been proven to be the only possible mechanism in the case of the soybean lipoxygenase.

The distribution of known enzyme catalytic rates ( k cat /K M ). Most enzymes have a rate around 10 5 s −1 M −1 . The fastest enzymes in the dark box on the right (>10 8 s −1 M −1 ) are constrained by the diffusion limit. (Data adapted from reference [ 1 ] )
An illustration to show (a) Alberty-Hammes-Eigen model, and (b) Chou's model, where E denotes the enzyme whose active site is colored in red, while the substrate S in blue.