ArticleMolecular and cellular biology2002
Maleylacetoacetate isomerase (MAAI/GSTZ)-deficient mice reveal a glutathione-dependent nonenzymatic bypass in tyrosine catabolism.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00865514 (Pharmacotoxicology of Trichloroethylene Metabolites), which is not on this map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pharmacotoxicology of Trichloroethylene Metabolites: Short-term Effect of DCA on in Vivo Tyrosine Catabolism and MAAI Expression
Who cites it
36 citing papers in PubMed, 93 citations in OpenAlex.
- Targeting GSTZ1 Sensitizes KRASG12C-Mutant Lung Cancer Cells by Overcoming Glutathione and Glycolysis Pathway Rewiring.Cancer research communications · 2026Article
- The pyruvate dehydrogenase kinase inhibitor dichloroacetate mitigates alcohol-induced hepatic inflammation and metabolic disturbances in mice.Hepatology communications · 2024Article
- Article
- New Cases of Maleylacetoacetate Isomerase Deficiency with Detection by Newborn Screening and Natural History over 32 Years: Experience from a German Newborn Screening Center.International journal of neonatal screening · 2024Article
- Signaling metabolite succinylacetone activates HIF-1α and promotes angiogenesis in GSTZ1-deficient hepatocellular carcinoma.JCI insight · 2023Article
- Regulating mitochondrial metabolism by targeting pyruvate dehydrogenase with dichloroacetate, a metabolic messenger.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- A DNA assembly toolkit to unlock the CRISPR/Cas9 potential for metabolic engineering.Communications biology · 2023Article
- A DNA assembly toolkit to unlock the CRISPR/Cas9 potential for metabolic engineering.Research square · 2023Article
- Chemical Proteomics with Novel Fully Functionalized Fragments and Stringent Target Prioritization Identifies the Glutathione-Dependent Isomerase GSTZ1 as a Lung Cancer Target.ACS chemical biology · 2023Article
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- New insights and advances on pyomelanin production: from microbial synthesis to applications.Journal of industrial microbiology & biotechnology · 2022Review
- Metabolic and Network Pharmacological Analyses of the Therapeutic Effect ofFrontiers in pharmacology · 2021Article
- Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis.Journal of inflammation research · 2021Article
- Effects of High-Fat Diet Induced Obesity and Fructooligosaccharide Supplementation on Cardiac Protein Expression.Nutrients · 2020Article
- Sequence identification and expression profile of seven Dermacentor marginatus glutathione S-transferase genes.Experimental & applied acarology · 2020Article
- Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1.Paediatric drugs · 2019Review
- GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.The EMBO journal · 2019Article
- Functional, Structural and Biochemical Features of Plant Serinyl-Glutathione Transferases.Frontiers in plant science · 2019Review
- Developmental roles of tyrosine metabolism enzymes in the blood-sucking insectProceedings. Biological sciences · 2017Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In mammals, the catabolic pathway of phenylalanine and tyrosine is found in liver (hepatocytes) and kidney (proximal tubular cells). There are well-described human diseases associated with deficiencies of all enzymes in this pathway except for maleylacetoacetate isomerase (MAAI), which converts maleylacetoacetate (MAA) to fumarylacetoacetate (FAA). MAAI is also known as glutathione transferase zeta (GSTZ1). Here, we describe the phenotype of mice with a targeted deletion of the MAAI (GSTZ1) gene. MAAI-deficient mice accumulated FAA and succinylacetone in urine but appeared otherwise healthy. This observation suggested that either accumulating MAA is not toxic or an alternate pathway for MAA metabolism exists. A complete redundancy of MAAI could be ruled out because substrate overload of the tyrosine catabolic pathway (administration of homogentisic acid, phenylalanine, or tyrosine) resulted in renal and hepatic damage. However, evidence for a partial bypass of MAAI activity was also found. Mice doubly mutant for MAAI and fumarylacetoacetate hydrolase (FAH) died rapidly on a normal diet, indicating that MAA could be isomerized to FAA in the absence of MAAI. Double mutants showed predominant renal injury, indicating that this organ is the primary target for the accumulated compound(s) resulting from MAAI deficiency. A glutathione-mediated isomerization of MAA to FAA independent of MAAI enzyme was demonstrated in vitro. This nonenzymatic bypass is likely responsible for the lack of a phenotype in nonstressed MAAI mutant mice.
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