Hopfield-Ninio scheme

The well-known Hopfield-Ninio scheme is usually given as the following sequence of reactions between enzyme and substrate leading to the formation of the product... 

Now we discuss a deficiency of the Hopfield-Ninio scheme. Over a wide range of conditions, the turnover number for the hydrolysis of ATP to AMP catalyzed by IRS in the presence of valine and tRNA is identical to that for the isoleucylation of tRNA catalyzed by the enzyme when the valine is replaced by [ C]Ile. This is possible only when the diserimination through hydrolysis occurs after the rate-limiting step. To the contrary, the KPR scheme proposed by Hopfield considers that the discrimination step will be before the rate-limiting product formation step. 

We first discuss the Hopfield-Ninio KPR scheme, which is followed by a critical analysis of the scheme in the light of the recent experimental results of... 

As mentioned above, the experimental results do not seem to support the picture of repeated activation as the mechanism of KPR. In an alternative scheme to the Hopfield-Ninio proposal, Fersht proposed that the repeated activation may not be required if the critical step involves an enhanced rate of hydrolysis of the wrong substrate. Fersht described two mechanisms as follows ... 

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