Lowered activation energy in enzymatic reactions

[TytoAlba95]

I was stuck with a question; how does enzyme lower the activation energy of a reaction. After several internet searches, I found a post in biostackexchange which partially clarified my question. I'll write my current understanding before I proceed to my actual question.

Activation energy is the energy required by reactants to reach a transition state. The transition state is a state of reactants in which old bonds are being broken and new bonds are being formed (say its a nucleophile substitution reaction). To reach this state, energy is needed (supplied in the form of heat). This heat energy is utilized to increase the kinetic energy of the molecules, such that the reactant molecules collide with each other in the proper orientation to form the T.S. (Not all molecules will have the sufficient energy or orientation to collide and form T.S.)

Now once the T.S. is formed it can either breakdown into products or reactants.

In case of an enzyme, the interaction of the reactants with the active site brings the reactant molecules close together and in the proper orientation for the T.S to form. Thus the energy needed for the reactant molecules to get converted into T.S (or product) is lowered.

As the conversion occurs pretty much automatically at the active site in normal physiological temperature, I do not understand why should there be any activation energy at all for enzyme catalysed reactions. Or maybe, I should say in what ways the reactants take up energy in enzymatic reactions.

 

[Ygggdrasil]

Energy provided by heat is essentially the energy available through collisions with other molecules in solution. For a reaction to be driven by thermal energy does not necessarily require one heating the solution. There is some amount of thermal energy available at room temperature and this is capable of driving some reactions with low activation energies to occur at a reasonable rate. Elevating the temperature increases the amount of thermal energy available in the solution and more reactions with higher activation energy can occur at a reasonable rate.

For an enzyme catalyzed reaction, the uncatalyzed reaction has a high activation energy that will occur only very slowly for the amount of thermal energy available at room temperature. Enzymes lower the activation energy such that the activation energy is comparable to the amount of thermal energy available at room temperature (or physiological temperatures such as 37°C) and the reaction can occur at a much faster rate.

 

[epenguin]

In case of an enzyme, the interaction of the reactants with the active site brings the reactant molecules close together and in the proper orientation for the T.S to form. Thus the energy needed for the reactant molecules to get converted into T.S (or product) is lowered.

As the conversion occurs pretty much automatically at the active site in normal physiological temperature, I do not understand why should there be any activation energy at all for enzyme catalysed reactions. Or maybe, I should say in what ways the reactants take up energy in enzymatic reactions.

Orienting the reactants as you say in your first paragraph is part of the explanation. But the part you are perhaps missing is that the enzyme forces the reactants into a structure that is closer to the transition state than is their structure when not bound to the enzyme. In other words the enzyme has more affinity for the transition state structure than it does to the native or solution structure of the reactants. So on binding the substrates are forced into conformations nearer to that of the transition state than they would otherwise be. The energy to transit into the transition state is thereby lowered.

You should familiarise yourself with the examples of known enzyme-substrate or enzyme-pseudosubstrate, enzyme-substrate analog, and particularly enzyme-transition state analog structures and example applications.

You may have some difficulty in picturing this. If the enzyme structure is complementary to that of the transition state not the native substrate,, then at the same time the native substrate structure should be pulling the enzyme out of this complementary conformation, or else having low-affinity. The answer is in a familiar but insufficiently often explained feature of enzymes. You often see that enzymatic reactivity depends on complicated molecular structures far from and seemingly irrelevant to the chemical reaction centre. E.g. Dehydrogenases that need the whole complicated dinucleotide structure of NAD or NADP and will not work or very little with just nicotinamide, the reactive part. Multiple specific bond 'anchorages' with the enzyme enables it to take the strain of distorting the enzyme-substate complex into the structure resembling transition statethe structure resembling transition state with a complementary protein structure fitting around it. Another very common phenomenon is seen on the specificity of many enzymes active on polymers, e.g. peptidases or nucleases. More often than not these other these are very little active on dipeptides or dinucleotides but active on larger polypeptides or polynucleotides. This again is down to enzyme anchorage to parts of the substrates distant from the chemically reacting part.