Reactivation and aging of diphenyl phosphoryl acetylcholinesterase

Biochim Biophys Acta. 1975 Oct 22;403(2):370-87. doi: 10.1016/0005-2744(75)90066-2.

Abstract

Acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) is readily in hibited by 10(-5) M diphenylphosphorochloridate even though the inhibitor hydrolyzes in a few seconds. The fluoridate is a much weaker inhibitor. The inhibited enzyme, diphenyl phosphoryl enzyme spontaneously recovers only about 50% of its activity with a half time of about 17 min at pH 7.0 and 6 min at pH 8.0. The fact that only 50% of the original activity returns is due to aging. The rates of reactivation and aging can be very greatly increased by a few percent of an organic solvent. Depending on the solvent even 1% may increase the rates by a factor of 5 or 6. The highest increase in rate was 70-fold. Quaternary NH+4 also increases the rates. Organic solvents and NH+4 also accelerate the reactivation of the much more stable diethyl phosphoryl enzyme derivative.

Publication types

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

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Binding Sites
  • Dimethyl Sulfoxide / pharmacology
  • Drug Stability
  • Eels
  • Hydrogen-Ion Concentration
  • Kinetics
  • Mathematics
  • Organophosphorus Compounds / pharmacology
  • Protein Binding
  • Solvents
  • Time Factors

Substances

  • Organophosphorus Compounds
  • Solvents
  • Acetylcholinesterase
  • Dimethyl Sulfoxide