Suicide inhibition

Suicide inhibition, also known as suicide inactivation or mechanism-based inhibition, is a form of enzyme inhibition that occurs when an enzyme binds a substrate analogue and forms an irreversible complex with it, which inactivates the enzyme permanently. This process is distinct from other forms of enzyme inhibition, such as competitive inhibition, non-competitive inhibition, and uncompetitive inhibition, which are reversible.

Mechanism

The mechanism of suicide inhibition involves the enzyme's catalytic cycle. The suicide inhibitor, which is a substrate analogue, is initially recognized and bound by the enzyme in the same way as its normal substrate. The enzyme then acts on the suicide inhibitor as if it were a normal substrate, forming a covalent bond with it. However, unlike a normal substrate, the suicide inhibitor cannot be converted into product and released. Instead, it remains covalently bound to the enzyme, permanently inactivating it.

Examples

One well-known example of suicide inhibition is the action of penicillin on the bacterial enzyme transpeptidase. Penicillin is structurally similar to the enzyme's natural substrate, the dipeptide D-Ala-D-Ala. When transpeptidase binds penicillin, it attempts to catalyze its conversion into product, but instead forms a stable covalent bond with penicillin, inactivating the enzyme and preventing the synthesis of bacterial cell walls.

Another example is the action of aspirin (acetylsalicylic acid) on the enzyme cyclooxygenase. Aspirin acetylates a serine residue in the active site of cyclooxygenase, preventing it from catalyzing the conversion of arachidonic acid to prostaglandin H2, a precursor of inflammatory mediators.

Clinical significance

Suicide inhibitors have important clinical applications, particularly in the field of pharmacology. Many drugs act as suicide inhibitors, including some antibiotics, antiviral drugs, and cancer chemotherapy agents. These drugs are designed to selectively inhibit specific enzymes in pathogenic organisms or cancer cells, thereby killing the cells or inhibiting their growth.

See also

• Enzyme inhibitor
• Enzyme kinetics
• Drug design