Difference between Competitive and Uncompetitive Enzyme Inhibition

There are four main types of enzyme inhibition: competitive, non-competitive, uncompetitive, and mixed inhibition. This post will discuss the main differences between Competitive and Uncompetitive in detail.

Competitive Inhibition

-Mechanism

The inhibitor and substrate compete for the same binding site (or the active site) on the enzyme. The inhibitor decreases the enzyme’s capacity to bind the substrate, but this impact may be counteracted by raising the substrate concentration.

-Effect on Enzyme Kinetics

1. V_max: V_max remains the same. The enzyme can still reach its maximum velocity if enough substrate is present to outcompete the inhibitor. (higher substrate concentration is required than the absence of inhibitor)
2. K_m: K_m increases. More substrate is needed to achieve half-maximal velocity because the inhibitor is blocking the active site.

-Lineweaver-Burk Plot

The inhibitor and no-inhibitor Lines intersect on the y-axis (1/V_max). while the slope of the inhibitor line increased because the k_m increased with the inhibitor.

Uncompetitive Inhibition

-Mechanism

The inhibitor binds only to the enzyme-substrate complex(not the free enzyme) and forms an inactive complex. After binding the substrate to the enzyme, the enzyme undergoes some changes in its 3D structure. These changes make the allosteric site available for the inhibitor to bind. This binding prevents the complex from proceeding to product formation, effectively reducing the enzyme’s activity.

-Effect on Enzyme Kinetics

• V_max: V_max decreases. The inhibitor effectively removes enzyme-substrate complexes from the reaction, reducing the overall enzyme activity.
• K_m: K_m decreases. The inhibitor shifts the equilibrium towards the formation of more enzyme-substrate complexes, making it appear as if the enzyme has a higher affinity for the substrate.

-Lineweaver-Burk Plot

The inhibitor and no-inhibitor Lines are parallel Because both the K_m and V_max indexes experienced a decrease.

Conclusion

The competitive inhibitor competes with the substrate to bind the enzyme, and it negatively impacts enzyme performance. Although a competitive inhibitor decreases the enzyme’s affinity to the substrate (K_m), the V_max remains stable. An uncompetitive inhibitor doesn’t compete with the substrate to bind the enzyme and connects to enzyme-substrate complexes. It negatively impacts enzyme performance by decreasing the V_max and enzyme affinity to the substrate.

Reference

1. Ring, B., Wrighton, S. A., & Mohutsky, M. (2014). Reversible Mechanisms of Enzyme Inhibition and Resulting Clinical Significance. Enzyme Kinetics in Drug Metabolism, 37–56. doi:10.1007/978-1-62703-758-7_4
2. Enzyme Inhibitors and Activators. Croatia, IntechOpen, 2017
3. Biorender.com
4. J. Chem. Educ.2000, 77, 11, 1453 Publication Date:November 1, 2000, https://doi.org/10.1021/ed077p1453