BIOLOGY Volume 1 - A Guide to General Biology - 2004

4. ENZYMES

4.4. Enzyme Inhibition

Various low-molecular-weight compounds are known to reduce The rate of enzyme-catalyzed reactions. Such compounds are called Enzyme Inhibitors. It is important to understand that inhibition is a normal mechanism for regulating enzyme activity. Many drugs and poisons also act as enzyme inhibitors. Inhibition can be either competitive or non-competitive. Non-competitive inhibition may be reversible or irreversible.

4.4.1. Competitive Inhibition

In this case, a substance structurally similar to the normal enzyme substrate binds to the Active Site of the enzyme but cannot react with it. Once there, it blocks access to the active site for any molecule of the actual substrate. Because the inhibitor and the substrate compete for the active site, this form of inhibition is called competitive inhibition. A characteristic feature of competitive inhibition is that increasing the Substrate Concentration causes the reaction rate to increase; in other words, this type of inhibition is reversible.

4.3. Why does the reaction rate increase under these conditions?

Fig. 4.12 illustrates an example of competitive inhibition.

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Fig. 4.12. Competitive inhibition. A. A simple diagram illustrating the inhibition mechanism. B. The enzyme succinate dehydrogenase catalyzes The conversion of succinic acid to fumaric acid. C. Competitive inhibition of the enzyme by malonic acid.

The phenomenon of competitive inhibition helps explain the MECHANISM OF ACTION of certain drugs, particularly sulfonamides. The goal of Chemotherapy is to destroy a pathogen using specific chemical agents without harming the Tissues of the host Organism. The first such drugs were the sulfonamides, whose antibacterial action was discovered in the 1930s. During World War II, they were widely used to combat wound infections. Structurally, sulfonamides are similar to Para-aminobenzoic Acid (PABA), an essential growth factor for many pathogenic Bacteria. Bacteria require PABA to synthesize Folic acid, which serves as one of their enzyme Cofactors. Sulfonamides inhibit one of the Enzymes involved in the synthesis of folic acid from PABA.

Animal Cells are insensitive to sulfonamides, even though they also require folic acid for certain reactions. This is because they utilize preformed Folic Acid and lack the metabolic pathway required for its synthesis.