Sequential enzyme-catalyzed metabolism of 4-nitrotoluene to S-(4-nitrobenzyl)glutathione
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Updated: Aug 2, 2026

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
Published on: September 25, 2017
Abstract:
[14C]-4-Nitrotoluene was metabolized by rat liver postmitochondrial supernatant containing NADPH, reduced glutathione and a sulfate activating system to 4-nitrobenzyl alcohol, 4-nitrobenzyl sulfate, and S-(4-nitrobenzyl) glutathione. Formation of both sulfur-containing metabolites was dependent on the presence of a sulfate activating system. These results suggest that the glutathione conjugate was derived from 4-nitrobenzyl sulfate. Reaction of 4-nitrobenzyl sulfate with glutathione was not detected in pH 7.4 buffer, but rat liver cytosol catalyzed the formation of the glutathione conjugate from 4-nitrobenzyl sulfate. These results show that 4-nitrotoluene is metabolized in rat liver by sequential side chain oxidation, sulfation, and glutathione conjugation. Furthermore, they indicate that, unlike certain other arylmethyl sulfates, 4-nitrobenzyl sulfate is not highly reactive.
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