Fig. 3.

Cellular uptake and elimination of ITCs and intracellular protein modification. ITCs (R-N=C=S) are believed to enter a cell by diffusion, but once in cell are rapidly accumulated via conjugation with intracellular thiols, primarily GSH but also proteins. The GSH conjugates may be further metabolized via the mercapturic acid pathway (‘R-NH-C(=S)-SR₁’ stands for these metabolites), which are expelled from the cell via membrane transporters. The conjugates may modify cellular proteins via exchange reactions with cysteine sulfhydryl groups. ITCs and their thiol conjugates may also bind to certain proteins via reaction with amino groups and may also cause protein thiol oxidation by stimulating cellular reactive oxygen species production.