ArticleDrug metabolism and disposition: the biological fate of chemicals2012
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.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Model Informed Dose Optimization of Dichloroacetate for the Treatment of Congenital Lactic Acidosis in Children.Journal of clinical pharmacology · 2018Trial
- Physiologically Based Pharmacokinetic Modeling in Neonates: Current Status and Future Perspectives.Pharmaceutics · 2023Review
- Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases.International journal of nanomedicine · 2023Review
- Effects of Multiple Doses of Dichloroacetate on GSTZ1 Expression and Activity in Liver and Extrahepatic Tissues of Young and Adult Rats.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Age-Related Changes in miRNA Expression Influence GSTZ1 and Other Drug Metabolizing Enzymes.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Pharmacokinetic and Biochemical Profiling of Sodium Dichloroacetate in Pregnant Ewes and Fetuses.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Mitochondrial Glutathione Transferase Zeta 1 Is Inactivated More Rapidly by Dichloroacetate than the Cytosolic Enzyme in Adult and Juvenile Rat Liver.Chemical research in toxicology · 2019Article
- A Time-Embedding Network Models the Ontogeny of 23 Hepatic Drug Metabolizing Enzymes.Chemical research in toxicology · 2019Article
- Age-Related Changes in Expression and Activity of Human Hepatic Mitochondrial Glutathione Transferase Zeta1.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Regulation of dichloroacetate biotransformation in rat liver and extrahepatic tissues by GSTZ1 expression and chloride concentration.Biochemical pharmacology · 2018Article
- Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.Pharmacology & therapeutics · 2017Review
- Pharmacogenetic considerations with dichloroacetate dosing.Pharmacogenomics · 2016Review
- The influence of human GSTZ1 gene haplotype variations on GSTZ1 expression.Pharmacogenetics and genomics · 2015Article
- Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes.BioMed research international · 2015Article
- Chloride and other anions inhibit dichloroacetate-induced inactivation of human liver GSTZ1 in a haplotype-dependent manner.Chemico-biological interactions · 2014Article
- Establishment of metabolism and transport pathways in the rodent and human fetal liver.International journal of molecular sciences · 2013Review
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Authors and funding
7 authors at 2 institutions in 1 country.
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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 years. GSTZ1 was then sustained at stable, yet variable, levels (median, 20.0 pmol/mg cytosol; range, 4.8-47.3 pmol/mg cytosol) until age 74 years. GSTZ1 activity with DCA was strongly associated with haplotype and expression level. Samples homozygous or heterozygous for GSTZ1A exhibited ∼3-fold higher DCA dechlorinating activity than samples carrying other alleles at a given level of expression. The correlations (r²) between activity and expression were 0.90 and 0.68, respectively, for GSTZ1A carriers (n = 11) and noncarriers (n = 61). GSTZ1 is expressed in mitochondria in addition to cytosol. The GSTZ1A allele exhibited similar effects in the mitochondrial fraction by conferring a higher activity with DCA. In summary, we report a neonatal onset and an age-related increase in GSTZ1 protein expression during human liver development. Haplotype influenced GSTZ1 activity with DCA but not protein expression.
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