Structural Biochemistry/Enzyme/Rate-limiting step

Introduction

Enzymes assist reactions and increase the speed of formation of the products by decreasing the activation energy required for a reaction. Most fundamentally, enzymes are still just mechanisms that react catalytically in a chemical equation. Therefore, enzyme reactions also possess the basics of these step-wise mechanism reactions which of course includes the rate-limiting or rate determining step.

It is simple to assume correctly that each step of the mechanism does not proceed at the same rate, and so the rate-limiting step is merely the one reaction of the mechanism that has the slowest rate of reaction. An amusing real-life analogy in the spirit of Black Friday is: say a complete reaction is the time it takes for all the shoppers to make their purchases in Circuit City, then the rate-limiting step would be the shopper who is most indecisive and buys the most stuff. If one was to view a reaction coordinate graph of the entire reaction, the rate-limiting step is usually the one with the highest activation energy hump or highest energy transition state.

Particularly, by Michaelis-Menten kinetics of enzymes, the rate-limiting step is usually the product formation step.

For example: The reaction NO2(g) + CO(g) → NO(g) + CO2(g) occurs in two elementary steps:

1. NO2 + NO2 → NO + NO3 (slow step)

2. NO3 + CO → NO2 + CO2 (fast step)

As the second step consumes the NO3 produced in the slow first step, it is limited by the rate of the first step. For this reason, the rate-determining step is reflected in the rate equation of a reaction. Another simple situation analogous to a rate-limiting step is a family of four getting ready to go somewhere. Regardless of how fast everyone else is, because the family has to wait for everyone, the slowest person is going to determine how fast everyone else will be able to leave the house.

The role of rate-limiting step

The concept of the rate-determining step is very important to the optimization and understanding of many chemical processes such as catalysis and combustion. Furthermore, it may help determine if that mechanism is correct for the reaction. This is because the rate law for the rate limiting step should equal the rate law for the reaction. If this is not the case, then either the experimental rate law was determined incorrectly or the proposed mechanism is wrong.

The role of the rate-limiting step also has application in the study of alcohol in people. The body will naturally convert alcohol (ethanol is the alcohol consumed in beverages) into acetaldehyde which is later converted into acetate. Once it is an acetate, the body can naturally dispose of the acetate through waste. This is two step process which is:

Alcohol --> Acetaldehyde (very fast) Acetaldehyde --> Acetate (very slow, rate-limiting step)

Since alcohol is converted into acetaldehyde quickly, consumption of too much alcohol will cause acetaldehyde to escape into the bloodstream. This acetaldehyde will build up much faster than it can be converted into acetate. Once acetaldehyde is in the bloodstream, physiological effects begin to show. Eventaully, the acetaldehyde is converted to acetate and the effects wear off. In this case, the rate-limiting step is the conversion of acetaldehyde to acetate since it is much slower and causes a buildup of acetaldehyde in the bloodstream.