Competitive inhibitors
Competitive inhibitors are one of three sub-categories of reversible enzyme inhibitors.
The intended substrate molecules may be blocked from access to the enzyme active site by the imitating competitive inhibitor. This process is possible as the size and shape of the competitive inhibitor is relatively similar to that of the substrate[1]. The presence of competitive inhibitors can decrease the rate of reaction as it reduces the number of available enzyme to bind with the substrate and hence the products also decreases. The rate of reaction can be increased again by increasing the substrate concentration. Binding to the active site of enzyme is however temporary, unlike irreversible inhibtors. The competitive inhibitors bind 1000 times tighter than the natural substrate binds[2].
Cellular Processes
In biological activities and reactions, competitive inhibitors can have significant consequences. In short, it can act as to halt a reaction pathway, such as the metabolic pathway or reduce the enzyme activity [3]. Given the complex nature of cellular processes, and the requirement of enzymes for these processes, competitive inhibitors play a major role and is of great interest to drug companies such as Glaxosmithkline.
Drugs
Synthesis of drugs involving competitive inhibitors is both intensively developed globally and is of widespread clinical use as therapeutics. Competitive inhibitor drug usage is extensive. Examples include Tamiflu: Flu, tetrahydrofolate: (anticancer drug), para aminobenzoic acid: antibiotic.
Substrate concentration increase:
Reducing the effect of a competitive inhibitor is carried out through increasing concentration of target substrate. If the concentration of the target substrate increases, it is more likely to collide successfully and bind with the enzyme active site. This process is relatively simple to show in a laboratory set up, and is frequently used in a College and University environment.
An increasing substrate concentration reduces the impact of the competitive inhibitor. Vmax value will be highest where substrate levels are high [4].
A competitive inhibitor binds tightly to an enzyme. This would result in less substrate molecules binding to the enzyme, hence the affinity for substrate to enzyme decreases giving a high Km value. To compensate for this, increasing substrate concentration would increase affinity[5].
High affinity- Low Km value
Low affinity- High Km value
References
- ↑ Talaro, KT, AT. (1999) Foundations in microbiology. Third edition. United States of America. The McGraw-Hill Companies, Inc. pg230
- ↑ Jeremy M.B., John L. T. and Lubert S. (2012) Biochemistry, 7th edition, U.S.A, Kate Ahr Parker. pg246
- ↑ Talaro, KT, AT. (1999) Foundations in microbiology. Third edition. United States of America. The McGraw-Hill Companies, Inc. pg230
- ↑ Pamela.C.Champe, Richard.A.Harvey, Denise.R.Ferrier, P.C, R.H, D.F. (2008) Biochemistry. Fourth Edition. United States of America. Lippincott Williams and Wilkins. Page 60
- ↑ Pamela.C.Champe, Richard.A.Harvey, Denise.R.Ferrier, P.C, R.H, D.F. (2008) Biochemistry. Fourth Edition. United States of America. Lippincott Williams and Wilkins. Page 60