GSTZ

GSTZ, or glutathione S-transferase zeta 1, is a cytosolic enzyme in humans that is also known as maleylacetoacetate isomerase (MAAI). It belongs to the zeta class of the glutathione S-transferase (GST) family and plays a dual role in metabolism and detoxification.

In the tyrosine and phenylalanine degradation pathways, GSTZ1 catalyzes the isomerization of maleylacetoacetate to fumarylacetoacetate, a key step in the catabolism of these amino acids. In addition, GSTZ1 participates in glutathione-dependent detoxification, contributing to the conjugation of certain electrophilic compounds, though its primary association is with the MAI activity in the tyrosine pathway rather than broad detoxification.

GSTZ1 is encoded by the GSTZ1 gene, located on chromosome 14q24.3. The enzyme is expressed mainly in the liver, with additional expression in kidney and intestine, and functions as a cytosolic homodimer typical of many GST enzymes. Genetic variation in GSTZ1 results in distinct haplotypes that can affect enzymatic activity and substrate metabolism. Common human haplotypes, such as GSTZ1*1, *2, *3, and *4, influence how individuals metabolize certain chemicals, including dichloroacetate and various xenobiotics, with implications for pharmacokinetics and toxicology.

Clinically, GSTZ1 polymorphisms are studied in pharmacogenomics to understand interindividual differences in drug response and in the metabolism of endogenous tyrosine intermediates. There is no widely recognized GSTZ1 deficiency syndrome, but variation in activity can modulate metabolic and toxicological outcomes.