Methyl linoleate ozonide: a substrate for rat glutathione S-transferases

R M Vos1, I M Rietjens, G M Alink

  • 1Department of Toxicology, Agricultural University, Wageningen, The Netherlands.

Insights

Glutathione S-transferases (GST) detoxify methyl linoleate ozonide (MLO) by reacting it with glutathione (GSH). This enzymatic activity, particularly by isoenzyme 2-2, suggests a protective role against lipid peroxidation products.

Area of Science:

  • Biochemistry
  • Enzymology
  • Toxicology

Background:

  • Glutathione S-transferases (GST) are crucial enzymes involved in detoxification.
  • Lipid peroxidation generates reactive species, including ozonides like methyl linoleate ozonide (MLO).
  • The interaction between GST and MLO toxicity was not fully elucidated.

Purpose of the Study:

  • To investigate the role of GST in reducing the toxicity of methyl linoleate ozonide (MLO).
  • To identify the specific GST isoenzymes involved and their catalytic activity towards MLO.
  • To characterize the reaction products and intermediates.

Main Methods:

  • Enzymatic assays using purified GST isoenzymes and MLO as substrate.
  • Identification of reaction products and intermediates using chromatographic and spectroscopic techniques.
  • Comparison of GST activity with known GST-peroxidase activity.

Main Results:

  • GST effectively catalyzed the reaction between MLO and reduced glutathione (GSH), reducing toxicity.
  • MLO was recognized as a substrate by both cytosolic and microsomal GST.
  • GST isoenzyme 2-2 exhibited the highest specific activity towards MLO.
  • Oxidized glutathione and aldehydes were identified as final products, with transient glutathione-conjugate intermediates.

Conclusions:

  • GST plays a significant role in detoxifying MLO, likely through a mechanism similar to GST-peroxidase activity.
  • The findings highlight the protective capacity of GST against reactive lipid peroxidation products.
  • Isoenzyme 2-2 is a key player in the GST-mediated detoxification of MLO.