Serum cholinesterase inhibition by boronic acids

Area of Science:

• Biochemistry
• Enzymology

Background:

• Serum cholinesterase (acylcholine acylhydrolase, EC 3.1.1.8) plays a crucial role in neurotransmission and drug metabolism.
• Understanding the active site of this enzyme is key to developing targeted inhibitors and therapeutic agents.

Purpose of the Study:

• To investigate the inhibitory effects of alkyl- and areneboronic acids on horse serum cholinesterase.
• To determine the binding site and mechanism of inhibition for these compounds.

Main Methods:

• Enzyme inhibition assays were performed using horse serum cholinesterase.
• A range of alkyl- and areneboronic acids were tested to determine their inhibitory potency (Ki values).
• Competitive kinetics and protection assays against phenylmethanesulfonyl fluoride were used to elucidate the binding mechanism.

Main Results:

• Boronic acids demonstrated reversible inhibition of horse serum cholinesterase with Ki values spanning from 6.2 mM (methaneboronic acid) to 3.1 µM (diphenylboric acid).
• Inhibition followed competitive kinetics, indicating binding at the enzyme's active center.
• Boronic acids conferred protection against inactivation by phenylmethanesulfonyl fluoride, further supporting active site binding.

Conclusions:

• Alkyl- and areneboronic acids are effective reversible inhibitors of horse serum cholinesterase.
• These findings confirm that boronic acids bind to the active center of the enzyme.
• Boronic acids represent valuable tools for further investigation of the serum cholinesterase active site structure and function.