Inactivation of monoamine oxidase B by benzyl 1-(aminomethyl)cyclopropane-1-carboxylate

  • Silverman R
  • Lu X
  • Blomquist G
 et al. 
  • 3


    Mendeley users who have this article in their library.
  • 11


    Citations of this article.


Monoamine oxidase (MAO) is a flavoenzyme that catalyzes the oxidation of various biogenic and xenobiotic amines. Benzyl 1-(aminomethyl)cyclopropane-1-carboxylate (1) was designed as a diactivated cyclopropane mechanism-based inactivator of MAO (Silverman, R.B.; Ding, C.Z.; Borrillo, J.L.; Chang, J.T. J. Am. Chem. Sec. 1993, 115, 2982). [1,1-2H2]-1 exhibits a deuterium isotope effect of 4.5 on inactivation, but in D2O the isotope effect is only 2.3. [1-3H]-1 and [1-14C]-1 were synthesized; upon inactivation of MAO, 1.1 and 2.0 equiv of radioactivity, respectively, are incorporated into the enzyme. Tritium, as3H2O, is released during inactivation with [1-3H]-1. The flavin absorption spectrum changes from that of oxidized to that of reduced flavin after inactivation; denaturation of the inactivated enzyme shows a reduced flavin spectrum, suggesting the formation of a modified flavin. Tryptic digestion of the enzyme labeled with [1-3H]-1 or [1-14C]-1, followed by HPLC analysis, monitoring at 450 nm (flavin), shows that the radioactivity comigrates with the 450 nm absorptions. The metabolites that are generated during in activation are benzyl 1-formylcyclopropane-1-carboxylate, benzyl alcohol, and 1-formylcyclopropane-1-carboxylic acid; no ring-cleaved products were detected. The partition ratio, as determined from the ratio of nonamines to enzyme, is 110. These results are rationalized in terms of a single-electron transfer mechanism leading to the imine of benzyl 1-formylcyclopropane-1-carboxylate, which alkylates the flavin coenzyme.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Richard B. Silverman

  • Xingliang Lu

  • Geri D. Blomquist

  • Charles Z. Ding

  • Shengtian Yang

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free