Describe the Mechanism of Enzyme Action

Enzymes are catalytic biomolecules that help increase the rate of chemical reactions. Their activity is activated by their binding to the substrate at the activation site.

Describe the Mechanism of Enzyme Action

Every enzyme binds to its substrate at a specific location known as the active site. The active site is a small fraction of the area, but it is a highly significant site. The enzyme binds to the active site with the help of non-covalent bonds such as van der Waals force, hydrophobic, hydrogen, or ionic bonds.

Enzyme binding is very specific, and the enzyme must fit like a glove to the substrate. The work mechanism of enzymes involves two types. Though they differ in how they shape the enzyme-substrate complex, the enzymes maintain their substrate specificity.

The enzyme binding is crucial as it can accelerate the enzyme activity by altering the conformation. Two models explain this process, which are detailed below.

Lock and Key Mechanism of Enzyme Action

There are different hypotheses on how an enzyme identifies the site and bind property to the specific sites. One such important hypothesis is the lock and key hypothesis.

The Lock and Key model of enzyme mechanism was proposed by Emil Fischer, a German chemist in 1898.
According to this, the enzyme and substrate are considered the lock and key, respectively, that will be specific to each other to fit properly. Every enzyme and its substrate will have a mutually compatible design or structure that will fit each other like a lock and key.
Here, the enzyme and the substrate will have complementary structures to enable them to form an enzyme-substrate complex that fits their specificities as a specific key fits into a lock.
The active site of the enzyme forms the ‘lock’ and the substrate will be the ‘key’ that fits into this lock.
The enzyme-substrate complex will continue to sustain until the substrate is converted into the desired products.
Once the products are formed, the complex dissociates itself to become free and will be available for further reactions.

The Lock and Key model proposes structural rigidity of the enzyme, which usually has a dynamic structure.

One of the main drawbacks of this hypothesis is the presence of compounds that have a similar structure to the enzyme. They may arrive and fit into the substrate, inhibiting enzymatic activity. This is called competitive inhibition. The binding of the competitive molecules at the active site forms the enzyme-inhibitors.

Pic Credit: Cooper GM

Induced Fit Model of Enzyme Action

The second hypothesis is the induced fit model. According to the induced-fit hypothesis, the enzyme molecule undergoes conformational changes to bind with the substrate at the active site. It means the enzymes are flexible and change this confirmation to fit with the conformation of the substrate.

The induced fit model of enzyme mechanism involves enzymes that do not have a specifically shaped active site.
It was Daniel E Koshland who proposed the induced fit model in 1959.
Here, the enzyme-substrate specificity is inapplicable as there are no complementary structures.
The enzyme in such cases will have flexible active sites that can change their configuration and mold to fit the substrates.
The configuration of the enzymes changes until it binds to the substrate properly as needed. At the same time, there will not be any major change in the enzyme conformation, but it will be subtle.
This change in conformation happens in such a way that it brings the catalytic group right opposite to the bonds in the substrate that need to be broken. It will help bring the substrate closer to the transition state with high energy.
The force formed due to the enzyme-substrate bond will exert pressure to form the products.

The induced fit model was more accepted as it shows the flexibility of enzymes and their dynamicity. It shows that enzymes are flexible to the transition state of the substrate rather than its structure. A substrate in its transition state binds tightly and lowers the activation energy (transition state refers to an intermediate state, where it rearranges its molecule to fit the enzyme).

References

Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. The Central Role of Enzymes as Biological Catalysts. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9921/
S. C Bhatla, M. A. Lal, Plant Physiology, Development and Metabolism, https://doi.org/10.1007/978-981-13-2023-1_1