Glutathione S-transferase zeta 1 (GSTZ1)

Glutathione S-transferase zeta 1 (GSTZ1) is a cytosolic enzyme belonging to the glutathione S-transferase superfamily, functioning both as a transferase (for detoxification reactions) and as maleylacetoacetate isomerase (MAAI), a key enzyme in the phenylalanine and tyrosine degradation pathway[2][4]. GSTZ1 mediates the glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate. It also catalyzes the conjugation of glutathione to various electrophilic substrates, contributing to cellular defense against oxidative and metabolic stress. GSTZ1 modulates sensitivity to chemotherapeutic agents such as dichloroacetate and sorafenib: loss or deficiency of GSTZ1 is implicated in cancer cell proliferation, resistance to ferroptosis, and tumor progression, in part via aberrant activation of the NRF2/IGF1R and NRF2/GPX4 axes, making it a potential therapeutic biomarker and target especially in hepatocellular carcinoma[1][2][3]. Genetic polymorphisms of GSTZ1 influence the metabolism of drugs like dichloroacetate and may affect toxicity and therapeutic response[4].

Other names

Maleylacetoacetate isomeraseGSTZ1-1MAAIMAIMAAIDS-(hydroxyalkyl)glutathione lyaseglutathione S-alkyltransferaseglutathione S-aralkyltransferaseglutathione S-aryltransferaseglutathione transferase zeta 1maleylacetone isomerase

DCA is inactivated by GSTZ1-mediated conversion to glyoxylate, affecting its anti-cancer effectiveness[3][4]. Sorafenib resistance is modulated by GSTZ1 status via the NRF2/GPX4 axis; GSTZ1 loss activates NRF2/GPX4, suppressing ferroptosis and chemotherapeutic effect[2].