Which of the following mechanisms are expected to lower the free energy of activation in a chemical reaction catalyzed by an enzyme?

Question options:

A. Donation of protons by a protonated histidine side chain to a water molecule to increase the nucleophilicity of the water molecule through general acid catalysis.

B. Formation of hydrogen bonds between a substrate and an enzyme to position a reactive nucleophilic group in one substrate in the right orientation and at the right distance for nucleophilic attack on an electrophilic group in a second substrate

C. Neutralizing or shielding the positive charge of a reactive substrate through the formation of charge-charge interactions between a metal ion bound to the enzyme and the positive charged group in the substrate.

D. Formation of a covalent intermediate through the attack of an electrophilic carbonyl carbon in a substrate by the deprotonated thiol group in the side chain of a cysteine residue in an enzyme

E. Formation of a hydrogen bond between a main chain amide functional group in an enzyme and a high-energy negatively charged oxyanion formed in the transition state of the reaction.

Formation of hydrogen bonds between a substrate and an enzyme to position a reactive nucleophilic group in one substrate in the right orientation and at the right distance for nucleophilic attack on an electrophilic group in a second substrate.

Explanation:

- By forming hydrogen bonds between the substrate and the enzyme, the enzyme can orient the reactive groups in the substrate properly for the reaction to occur efficiently.

- Proper orientation reduces the free energy of activation by stabilizing the transition state, making it easier for the reaction to proceed.

- This mechanism enhances the specificity and efficiency of the enzyme in catalyzing the reaction, leading to a lower free energy of activation.

The other options describe various mechanisms involved in enzyme catalysis, but option B specifically addresses the formation of hydrogen bonds to position reactive groups, which plays a crucial role in lowering the free energy of activation in a catalyzed reaction.