GSTZ1

Glutathione S-transferase zeta 1 (GSTZ1), also known as maleylacetoacetate isomerase (MAAI), is a dual-function enzyme. It catalyzes the isomerization of maleylacetoacetate to fumarylacetoacetate— a key step in tyrosine and phenylalanine catabolism. As a glutathione S-transferase family member, it also conjugates glutathione to electrophilic substrates, aiding xenobiotic detoxification.
GSTZ1 mutations cause hereditary tyrosinemia type I (HT1), a rare metabolic disorder leading to liver/kidney damage via toxic metabolite accumulation. The main therapy is nitisinone, which inhibits upstream 4-hydroxyphenylpyruvate dioxygenase to reduce toxic intermediates, though it requires strict dietary tyrosine restriction. No targeted GSTZ1 replacement therapies are currently approved, but research on enzyme replacement is ongoing.