The correct answer is (4) The given brominated compound binds to triose phosphate isomerase at the active site and covalently modifies a glutamic acid residue required for enzyme activity.

Introduction

Enzyme inhibition plays a pivotal role in biochemistry, pharmacology, and metabolism, often exploited for therapeutic design and experimental probing of enzyme mechanisms. Inhibitors may bind reversibly or covalently, sometimes mimicking transition states or selectively reacting with functional residues at the active site. One classic example is the use of analogs targeting specific catalytic residues, such as glutamate in triose phosphate isomerase. This article compares several inhibition strategies and highlights correct scientific details regarding classic inhibitors.

Analysis of the Statements

(1) Iodoacetamide inactivates an enzyme by reaction with a critical serine residue at neutral pH.

• Incorrect:

  • Iodoacetamide is a sulfhydryl-reactive reagent, typically targeting cysteine residues, not serine.

  • Serine can be targeted by other reagents like diisopropyl fluorophosphate.

(2) Proline racemase causes isomerization of L-proline to D-proline. Ribose will be an appropriate transition state analog.

• Incorrect:

  • Ribose is structurally unrelated to the transition state of proline racemization.

  • Appropriate analogs mimic the transition state of the specific substrate, in this case proline, not ribose.

(3) Tosyl-1-phenylalanine chloromethyl ketone binds at the active site of chymotrypsin and modifies an essential arginine residue.

• Incorrect:

  • This compound binds to the chymotrypsin active site and alkylates a histidine or serine residue, not arginine.

(4) The given brominated compound binds to triose phosphate isomerase at the active site and covalently modifies a glutamic acid residue required for enzyme activity.

• Correct:

  • The brominated compound mimics the substrate and covalently modifies the essential glutamate residue (e.g., Glu-165 in TPI), irreversibly inactivating the enzyme.

  • This is a classic example of targeted covalent inhibition leveraging substrate analogs.

Covalent Modification and Enzyme Inhibition

• Covalent inhibitors form permanent bonds with key residues, halting enzyme activity.

• Trioso phosphate isomerase is commonly inhibited using substrate analogs or reactive compounds targeting its critical glutamate.

Importance of Transition State Analogs

• Highly effective inhibitors mimic the unstable transition state of reactions, binding more tightly than either substrate or product.

• Used therapeutically to block enzyme function or experimentally to map catalytic residues.

Summary Table

Conclusion

The correct statement is (4): the provided brominated compound inactivates triose phosphate isomerase by covalently modifying a glutamic acid residue essential for its catalytic activity. This classic mechanism exemplifies precise, irreversible inhibition at the active site using substrate-mimetic compounds.