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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.
Abstract:
Glutathione S-transferases (GST) were shown to be capable of reducing the toxicity of the ozonide of methyl linoleate (MLO) by catalyzing its reaction with reduced glutathione (GSH). MLO was a substrate for both cytosolic and microsomal GST. Isoenzyme 2-2 demonstrated the highest specific activity. Oxidised glutathione and aldehydes were identified as products of the reaction, with unstable glutathione-conjugates being formed as intermediates only. It was concluded that the GST-activity toward MLO may be similar to the GST-peroxidase activity with lipid hydroperoxides as substrates.
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.
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