Prenatal and postnatal expression of glutathione transferase ζ 1 in human liver and the roles of haplotype and subject age in determining activity with dichloroacetate.

ABSTRACT: Glutathione transferase ζ 1 (GSTZ1), also known as maleylacetoacetate isomerase, catalyzes the penultimate step of tyrosine catabolism and metabolizes several α-halocarboxylic acids, including dichloroacetic acid (DCA), an investigational drug used for lactic acidosis and, recently, solid tumors. Age-related differences have been suggested in DCA pharmacotoxicology, but no information is available on GSTZ1 ontogeny in humans. Here, we investigated the cytosolic GSTZ1 developmental expression pattern and the influence of haplotype on GSTZ1 activity with DCA by using human livers from donors between 10 weeks gestation and 74 years. GSTZ1 expression was very low in fetal livers (<2 pmol of GSTZ1/mg cytosol). The expression began to increase after birth in an age-dependent manner until age 7 y

SUBMITTER: Li W 

PROVIDER: S-EPMC3263939 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature