Engineering of human cholinesterases explains and predicts diverse consequences of administration of various drugs and poisons

Pharmacol Ther. 1995;67(2):283-322. doi: 10.1016/0163-7258(95)00019-d.


The acetylcholine hydrolyzing enzyme, acetylcholinesterase, primarily functions in nerve conduction, yet it appears in several guises, due to tissue-specific expression, alternative mRNA splicing and variable aggregation modes. The closely related enzyme, butyrylcholinesterase, most likely serves as a scavenger of toxins to protect acetylcholine binding proteins. One or both of the cholinesterases probably also plays a non-catalytic role(s) as a surface element on cells to direct intercellular interactions. The two enzymes are subject to inhibition by a wide variety of synthetic (e.g., organophosphorus and carbamate insecticides) and natural (e.g., glycoalkaloids) anticholinesterases that can compromise these functions. Butyrylcholinesterase may function, as well, to degrade several drugs of interest, notably aspirin, cocaine and cocaine-like local anesthetics. The widespread occurrence of butyrylcholinesterase mutants with modified activity further complicates this picture, in ways that are only now being dissected through the use of site-directed mutagenesis and heterologous expression of recombinant cholinesterases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Carbamates*
  • Central Nervous System Diseases / enzymology
  • Cholinesterase Inhibitors / toxicity*
  • Cholinesterases / chemistry
  • Cholinesterases / drug effects
  • Cholinesterases / genetics*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / genetics*
  • Humans
  • Insecticides / adverse effects*
  • Mutagenesis, Site-Directed
  • Organophosphorus Compounds*
  • Protein Engineering
  • RNA Splicing
  • Recombinant Proteins / genetics


  • Carbamates
  • Cholinesterase Inhibitors
  • Insecticides
  • Organophosphorus Compounds
  • Recombinant Proteins
  • Cholinesterases