MoBio Catalytic Mechanisms of Enzymes Chapter 2

From the energetic point of view, the reason why an enzyme can accelerate a reaction is because it can lower the energy barrier (activation energy) separating the substrate and the reaction product. For example, the covalent bond energy between two atoms ranges from 50 to 200 kcal/mol, which is far greater than the thermal energy (0.6 kcal/mol) at room temperature. Therefore, the covalent bond is unlikely to break in the absence of external interactions. Enzymes can provide a proper environment to lower the energy barrier.

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Figure 2-E-3. The free energy profile of an enzymatic reaction. The substrate S is the molecule on which an enzyme acts. P represents the reaction product. The horizontal axis (reaction coordinate) reflects the progressive change from S to P.

The exact mechanism of lowering the energy barrier depends on individual systems. RNase A is a very interesting example. This enzyme can cleave an RNA molecule through hydrolysis reaction, but has no effect on DNA. In Chapter 3, we shall see that DNA and RNA differ by only one oxygen atom, which happens to play a critical role in the catalytic mechanism of RNase A.

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Figure 2-E-4. (a) The hydrolysis reaction catalyzed by RNase A. An RNA molecule is a chain of nucleotides linked by the phosphodiester bond, which may be cleaved by RNase A. This figure shows only two nucleotides adjacent to the cleavage site. (b) The intermediate product (transition state) of this reaction.

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Figure 2-E-5. The catalytic mechanism of RNase A, which contains two critical residues: His-12 and His-119. (a) The transition state is formed by electron transfer from His-12 to His-119, passing through 2'-OH. (b) After the transition state is formed, the electron can move from His-119 to His-12, generating the final product. DNA lacks the critical 2'-OH and thus cannot be catalyzed by RNase A.