Paraoxon, 4-nitrophenyl phosphate and acetate are substrates of α- but not of β-, γ- and ζ-carbonic anhydrases

Bioorg Med Chem Lett. 2010 Nov 1;20(21):6208-12. doi: 10.1016/j.bmcl.2010.08.110. Epub 2010 Aug 26.

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) belonging to α-, β-, γ- and ζ-classes and from various organisms, ranging from the bacteria, archaea to eukarya domains, were investigated for their esterase/phosphatase activity with 4-nitrophenyl acetate, 4-nitrophenyl phosphate and paraoxon as substrates. Only α-CAs showed esterase/phosphatase activity, whereas enzymes belonging to the β-, γ- and ζ-classes were completely devoid of such activity. Paraoxon, the metabolite of the organophosphorus insecticide parathione, was a much better substrate for several human/murine α-CA isoforms (CA I, II and XIII), with k(cat)/K(M) in the range of 2681.6-4474.9M(-1)s(-1), compared to 4-nitrophenyl phosphate (k(cat)/K(M) of 14.9-1374.4M(-1)s(-1)).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Dioxide / metabolism
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrases / metabolism*
  • Catalysis
  • Humans
  • Insecticides / metabolism*
  • Isoenzymes / metabolism
  • Kinetics
  • Mice
  • Nitrophenols / metabolism*
  • Organophosphorus Compounds / metabolism*
  • Paraoxon / metabolism*
  • Substrate Specificity

Substances

  • Carbonic Anhydrase Inhibitors
  • Insecticides
  • Isoenzymes
  • Nitrophenols
  • Organophosphorus Compounds
  • Carbon Dioxide
  • nitrophenylphosphate
  • 4-nitrophenyl acetate
  • Carbonic Anhydrases
  • Paraoxon