Enzyme Activity: Factors, Inhibition, and Metabolic Control

Factors Affecting Enzyme Activity

pH Effects on Enzyme Function

Enzymes exhibit an optimum pH at which their activity is maximal, characterized by a low K_m (substrate concentration) and maximum velocity. Small variations around this optimum pH value cause a sudden drop in activity. This can be due to the appearance or disappearance of electrostatic forces that alter the spatial structure of the active site, or changes in the charges of the active center and substrate, which affect their binding capacity. If the pH change is very high, the enzyme is denatured and ceases to be functional.

Temperature's Role in Enzyme Kinetics

In general, an increase in temperature increases the rate of chemical reactions. In the case of enzyme-catalyzed reactions, activity typically doubles with every 10°C increase in temperature, up to a maximum activity value around 40°C. Beyond this value, enzyme activity decreases rapidly due to the loss of the enzyme's tertiary structure (denaturation). At lower temperatures, a reduction in molecular vibration slows down the reaction rate, affecting substrate binding and overall reaction speed.

Enzyme Inhibitors: Types and Mechanisms

Inhibitors are chemical substances that decrease or block enzyme activity. Depending on their action, there are two main types of inhibition:

• Irreversible Inhibition: Occurs when the inhibitor's effect is permanent. The inhibitor binds covalently to the enzyme, permanently altering its structure and catalytic activity.
• Reversible Inhibition: Occurs when the effect is temporary and does not destroy the enzyme's catalytic activity. The binding involves non-covalent bonds, which are weaker and easier to break. The enzyme regains its activity once the inhibitor is removed.

Reversible Inhibition Subtypes

Within reversible inhibition, we distinguish two types:

• Competitive Inhibition:

  In this type, both the substrate and the inhibitor can bind to the enzyme's active site. If the substrate binds, products are formed. However, if the inhibitor binds, no reaction occurs. Its effect is lessened by increasing the substrate concentration. The degree of inhibition depends on the relative proportion between the substrate and the inhibitor. For competitive inhibition to occur, the inhibitor must be able to bind to the active site, meaning it must have a strong structural resemblance to the substrate (substrate analogues).

• Non-Competitive Inhibition:

  Here, the inhibitor binds to the enzyme at a site different from the active site where the substrate binds. This binding alters the enzyme's conformation, preventing the substrate from binding effectively to the active site or affecting its catalytic efficiency. An increase in substrate concentration does not lead to the recovery of enzyme activity in this case.

Regulation of Enzyme Activity in Metabolic Pathways

In cellular metabolism, enzymes often act in sequential groups to carry out a metabolic process. In these chains (metabolic pathways), the product of the first enzyme's reaction becomes the substrate for the next, and so on. The first enzyme in a metabolic pathway is often the primary regulatory point. Subsequent enzymes only promote their reactions when their substrates, formed in earlier stages, are available. The enzyme is inhibited when it is no longer necessary to produce more of a certain product, and this product often acts as the inhibitor itself (feedback inhibition).