Related Experiment Videos
Human glutathione transferase zeta
1Molecular Genetics Group, John Curtin School of Medical Research, Australian National University, CAnaberra, Australia.
Methods in Enzymology
|January 10, 2006
Summary
Zeta-class glutathione transferases (GSTZs) are crucial for metabolizing dichloroacetic acid (DCA) and play a role in tyrosine degradation. Genetic variants and inactivation impact their function in humans and mice.
Area of Science:
- Biochemistry
- Enzymology
- Pharmacology
Background:
- Zeta-class glutathione transferases (GSTZs) were identified via bioinformatics.
- GSTZs exhibit unique catalytic activities beyond conventional GST substrates.
Purpose of the Study:
- Investigate the role of GSTZ in dichloroacetic acid (DCA) metabolism and tyrosine degradation.
- Characterize GSTZ substrate selectivity, inactivation mechanisms, and polymorphic variants.
- Utilize Gstz1 knockout mice to study in vivo functions.
Main Methods:
- Enzyme activity assays with various substrates including DCA.
- Proteomic analysis to identify protein modifications.
- Bioinformatic analysis of GSTZ gene variants.
- Phenotypic analysis of Gstz1 knockout mice.
Main Results:
- GSTZ catalyzes DCA oxygenation and maleylacetoacetate isomerization.
- GSTZ biotransforms various alpha-haloacids.
- DCA is a mechanism-based inactivator of GSTZ, covalently modifying Cys-16.
- Polymorphic GSTZ variants show altered catalytic rates and inactivation susceptibility.
- Gstz1 knockout mice lack DCA and maleylacetone biotransformation capacity.
Conclusions:
- GSTZ is vital for alpha-haloacid metabolism and tyrosine degradation.
- DCA metabolism by GSTZ is subject to genetic variation and inactivation.
- Gstz1 knockout mice provide a valuable model for studying GSTZ functions.