Literature summary for 5.2.1.2 extracted from

Shroads, A.L.; Langaee, T.; Coats, B.S.; Kurtz, T.L.; Bullock, J.R.; Weithorn, D.; Gong, Y.; Wagner, D.A.; Ostrov, D.A.; Johnson, J.A.; Stacpoole, P.W.
Human polymorphisms in the glutathione transferase zeta 1/maleylacetoacetate isomerase gene influence the toxicokinetics of dichloroacetate (2012), J. Clin. Pharmacol., 52, 837-849.

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Application

Application	Comment	Organism
additional information	knowledge of the GSTz1/MAAI haplotype can be used prospectively to identify individuals at potential risk of dichloroacetates adverse side effects from environmental or clinical exposure or who may exhibit aberrant amino acid metabolism in response to dietary protein	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
gene GSTz1/MAAI is located on chromosome 14q24.3, genotyping, overview	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
Dichloroacetate	the sensitivity to the inhibitor varies between enzyme haplotypes. Three nonsynonymous single-nucleotide polymorphisms of GSTz1/MAAI show different activity toward dichloroacetate and certain other xenobiotic haloacids	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	the bifunctional enzyme dehalogenates dichloroacetate to glyoxalate via its zeta-1 family glutathione transferase activity. Dichloroacetate is relevant to environmental science and allopathic medicine. The sensitivity to the inhibitor varies between enzyme haplotypes. Three nonsynonymous single-nucleotide polymorphisms of GSTz1/MAAI show different activity toward dichloroacetate and certain other xenobiotic haloacids	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
glutathione transferase zeta 1/maleylacetoacetate isomerase	-	Homo sapiens
GSTz1/MAAI	-	Homo sapiens
MAAI	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	human polymorphisms in the glutathione transferase zeta 1/maleylacetoacetate isomerase gene influence the toxicokinetics of dichloroacetate, GSTz1/MAAI haplotype significantly affects the kinetics and biotransformation of dichloroacetate. GSTz1/MAAI variants associated with the slowest rates of dichlorocacetate metabolism induce structural changes in the enzyme homodimer, predicting protein instability or abnormal protein-protein interactions. Enzyme inhibition also results in the accumulation of the potentially hepatotoxic tyrosine intermediates maleylacetoacetate and maleylacetone and of delta-aminolevulinate	Homo sapiens
metabolism	the bifunctional enzyme glutathione transferase zeta/maleylacetoacetate isomerase is the penultimate enzyme in the phenylalanine/tyrosine catabolic pathway	Homo sapiens

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Release 2023.1 (January 2023)