**4.1 The involvement of phytochelatin synthase in the catabolism of glutathione derivates**

PCS has a broad substrate selectivity and can use GS-derivates as substrates. For example, PCS isolated from plant species can accept *S*-alkylated GSH such as *S*-methyl-GS and *S*-hexyl-GS [6, 95] and large side residues like xenobiotic GS-conjugates (abbreviated as GS-conjugates) [17, 19, 20]. The bulky *S*-residues of GSH that can be converted to γ-Glu-Cys-conjugates by PCS include benzyl-, nitrophenyl-, phenylbenzyl-, uracil-, bimane-, and acetamido-fluorescein-groups [17, 19]. However, when PCS uses GS-derivates with these bulky *S*-linked side residues, it tends to transfer the γ-Glu-Cys-conjugate intermediate to a hydrogen group [17, 19, 20]. As a result, PCS processes the hydrolysis of GS-conjugates instead of their polymerization.

Besides its significant role in heavy metal detoxification, PCS also participates in the biodegradation of xenobiotic compounds because of its capability to process GS-conjugates [17–20]. Glutathione conjugation is a major pathway to inactivate xenobiotic compounds in plant cells [7]. Glutathione transferase (GST) detoxifies xenobiotics in the cytosol by transferring these compounds to GSH [10, 11, 96, 97]. These GS-conjugates enter vacuoles rapidly for sequestration and further degradation [12, 13]. In Arabidopsis, the transport of GS-conjugates for vacuolar sequestration

is facilitated by AtABCC1/AtMRP1 and AtABCC2/AtMRP2, which also transfer PC-metal complexes into vacuoles [12, 13, 22, 24]. Because of the high efficiency of this sequestration mechanism, the subsequent catabolism of GS-conjugates is presumably processed in the vacuoles [18]. First, vacuolar γ-glutamyl-transpeptidase (GGT) initializes the degradation of GS-conjugates by removing the γ-Glu-residue from the GS-conjugates to form Cys-Gly-conjugates [14, 15], and then, carboxypeptidase cleaves the Gly residue and results in the accumulation of the Cys-conjugates [16]. Alternatively, the GS-conjugate degradation can be initiated by PCS when vacuolar sequestration is not an available route [17–20]. The pathways of GS-conjugate metabolism are summarized in **Figure 1**.
