H2 Biology Core 1 - Enzyme Kinetics and Inhibition

Step 1 - Introduce enzymes as biological catalysts

Enzymes are biological catalysts that speed up metabolic reactions without being consumed.

Step 1 - Introduce enzymes as biological catalysts

They achieve this by lowering the activation energy of the reaction.

Step 1 - Introduce enzymes as biological catalysts

Each enzyme has a specific three dimensional shape, and the region where the substrate binds is called the active site.

Step 1 - Introduce enzymes as biological catalysts

Today we will explore how enzyme activity changes with substrate concentration, and what happens when inhibitors are present.

Step 2 - The lock-and-key versus induced fit models

The lock and key model proposes that the substrate fits perfectly into the active site, like a key into a lock.

Step 2 - The lock-and-key versus induced fit models

However, the induced fit model is more accurate.

Step 2 - The lock-and-key versus induced fit models

In this model, the active site changes shape slightly when the substrate binds, wrapping around it to form the enzyme substrate complex.

Step 2 - The lock-and-key versus induced fit models

This conformational change puts strain on the substrate bonds, lowering the activation energy even further.

Step 3 - Effect of substrate concentration on reaction rate

At low substrate concentration, there are many unoccupied active sites, so increasing substrate concentration increases the rate of reaction proportionally.

Step 3 - Effect of substrate concentration on reaction rate

As concentration rises further, more active sites become occupied and the rate increase slows down.

Step 3 - Effect of substrate concentration on reaction rate

Eventually, all active sites are saturated and the rate reaches a maximum called V max.

Step 3 - Effect of substrate concentration on reaction rate

At this point, adding more substrate has no effect because every enzyme molecule is already working at full capacity.

Step 4 - Competitive inhibition

A competitive inhibitor has a shape similar to the substrate and competes for the active site.

Step 4 - Competitive inhibition

When the inhibitor occupies the active site, the substrate cannot bind, so the reaction rate decreases.

Step 4 - Competitive inhibition

However, competitive inhibition can be overcome by increasing substrate concentration.

Step 4 - Competitive inhibition

On a graph, V max stays the same but more substrate is needed to reach it, so the apparent K m increases.

Step 5 - Non-competitive inhibition

A non competitive inhibitor binds to an allosteric site, which is a region away from the active site.

Step 5 - Non-competitive inhibition

This binding changes the shape of the active site so the substrate can no longer form an effective enzyme substrate complex.

Step 5 - Non-competitive inhibition

Because the inhibitor does not compete with the substrate, increasing substrate concentration cannot overcome the effect.

Step 5 - Non-competitive inhibition

On a graph, V max decreases but K m remains unchanged, since the remaining functional enzymes still have the same affinity for the substrate.

Step 6 - Comparing inhibition types and exam application

To distinguish the two types in an exam, look at the graph data.

Step 6 - Comparing inhibition types and exam application

If V max is the same but the curve is shifted to the right, that is competitive inhibition.

Step 6 - Comparing inhibition types and exam application

If V max is lower but the curve shape and K m are unchanged, that is non competitive inhibition.

Step 6 - Comparing inhibition types and exam application

A classic example is malonate, which competitively inhibits succinate dehydrogenase in the Krebs cycle because malonate resembles succinate.