A bienzyme electrochemical probe for flow injection analysis of okadaic acid based on protein phosphatase-2A inhibition: an optimization study

Anal Biochem. 2009 Feb 1;385(1):50-6. doi: 10.1016/j.ab.2008.10.027. Epub 2008 Oct 26.

Abstract

A bienzyme electrochemical probe has been assembled and used to monitor the inhibition of the enzyme protein phosphatase-2A (PP2A) by okadaic acid (OA), taking advantage of the particular characteristics of a biochemical pathway in which PP2A is involved. This enzyme has significant activity toward glycogen phosphorylase a (PHOS a), which in turn catalyzes the conversion of glycogen to glucose-1-phosphate (G-1-P). In addition, PP2A is strongly inhibited by OA and its derivatives. Due to this combination of properties, PP2A was employed to develop an assay system involving a preliminary phase of off-line enzymatic incubations (OA/PP2A, PP2A/PHOS a, PHOS a/glycogen+phosphate). This off-line step was followed by the electrochemical detection of H2O2, which is the final product of two sequential enzymatic reactions: G-1-P with alkaline phosphatase (AP) producing glucose, then glucose with glucose oxidase (GOD) producing hydrogen peroxide. These two enzymes were coimmobilized on a nylon net membrane that was placed over an H2O2 platinum probe inserted into a flow injection analysis (FIA) system. During a first phase of the study, all analytical parameters were optimized. During a subsequent phase, the inhibition of PP2A enzyme by OA was evaluated. The calibration of the system shows a working range for detection of OA between 30 and 250 pg ml(-1). The total analysis time is the sum of 50 min for the off-line enzymatic incubations and 4 min for the biosensor response.

MeSH terms

  • Biosensing Techniques / instrumentation
  • Biosensing Techniques / methods*
  • Electrochemistry
  • Electrodes
  • Enzyme Inhibitors / analysis*
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Stability
  • Flow Injection Analysis / instrumentation
  • Flow Injection Analysis / methods*
  • Glycogen / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Okadaic Acid / analysis*
  • Okadaic Acid / pharmacology*
  • Osmolar Concentration
  • Phosphates / chemistry
  • Protein Phosphatase 2 / antagonists & inhibitors*
  • Protein Phosphatase 2 / metabolism
  • Sensitivity and Specificity

Substances

  • Enzyme Inhibitors
  • Phosphates
  • Okadaic Acid
  • Glycogen
  • Protein Phosphatase 2