TBR - Enzyme's rate determining step, which step is it?

[Monkeymaniac]

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In TBR woorkbook, it has several conflicting sources which tell what practically determnines the rate of the enzymatic reaction (rate-determining step). They are all written in "Metabolic Components" chapter passages.

1. One source (passage I) states, after giving background information on the Michaelis-Menten equation, that rate of a reaction is generally determined by . Which I thought made sense, since from v=Vmax/(Km+), if we keep the environment (temperature, pH, etc) the same and also the concentration of enzyme, the only variable here is , substrate concentration.

2. The other source (passage VI) tells that the second step of the enzymatic reaction, E+S<->ES->E+P, namely the conversion of enzyme-substrate complex to product is a rate-determining step.

3. Finally, passage XV says that the step which is rate-determining in many enzyme-catalyzed reactions is due to the collisiobn frequency of enzyme and substrate, rather than the actual enzymatic function of the enzyme.

So I think 1 and 3 are basically stating the same thing, but they are definitely contradicting what's stated in 2. Which one is right? In the real thing, it might be explained like in the TBR passages, but I wanted to find out now than getting anxious later on. Thanks in advance.

 

[lorenzomicron]

A general rule is that the rate determining step has the most change in free energy in a reaction coordinate, which is here chosen to be state of molecule (unbound, bound, final).

Since the enzyme-substrate or transition-state complex in a reaction which is non-spontaneous has more energy than the initial state due to the absorption of some activation energy and also the product usually has significantly less free energy, the rate determining step must always be step from transition-state to product.

 

[addo]

The rate determining step can fall into two categories: Activation controlled limit, and diffusion-controlled limit.

In the diffusion controlled limit, the rate of the reaction is controlled by the rate at which the reactants diffuse together, as once they have encountered each other, the reaction is so fast that they will certainly go on to form products, rather than diffuse apart. This is point 3 in your list.

In activation controlled limit, the reaction rate depends on the rate at which energy accumulates in the encounter pair. In this case, simply the encounter of reactants will not necessarily lead to product formation. This is essentially point 2 in your list.

There is no contradiction, it just depends on the reaction.