Disease relevance of GSTZ1

• CONCLUSION: Statistical analysis indicates that there is no association of the GSTZ1 variant and hence the gene does not appear to play a significant role in the development of sporadic breast cancer [1].
• CONCLUSION: These SNPs may alter GSTZ1 expression, which may alter the pharmacokinetics of DCA, which is used therapeutically for the treatment of lactic acidosis [2].
• Human MAAI deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone, the diagnostic compound resulting from fumarylacetoacetate hydrolase deficiency in humans and fungi [3].
• They encode a protein with 45% sequence identity to MaiA, which showed MAAI activity when expressed in E. coli [3].
• We report here the first characterization of a gene encoding a MAAI enzyme from any organism, the A. nidulans maiA gene. maiA disruption prevents growth on phenylalanine (Phe) and phenylacetate and results in the absence of MAAI activity in vitro and Phe toxicity [3].

High impact information on GSTZ1

• The second enzyme, a reductive dehalogenase, may have evolved from a maleylacetoacetate isomerase normally involved in degradation of tyrosine [4].
• We use here an identical approach to characterize at the cDNA level the human gene for maleylacetoacetate isomerase (MAAI, EC 5.2.1.2), the only as yet unidentified structural gene of the phenylalanine catabolic pathway [3].
• The MaiA protein shows strong amino acid sequence identity to glutathione S-transferases and has MAAI activity when expressed in Escherichia coli. maiA is clustered with fahA and hmgA, the genes encoding the two other enzymes of the common part of the Phe/phenylacetate pathways [3].
• CMVE was accompanied by prominent systemic CMV infection at autopsy, including CMV adrenalitis (92%), CMV pneumonitis (42%), systemic Mycobacterium avium intracellulare (MAI; 58%), and CMV retinitis (58%) [5].
• Hyponatremia and MAI bacteremia were found in 58% of CMVE cases [5].

Chemical compound and disease context of GSTZ1

• Clinically relevant doses of DCA (mg/kg/day) decrease the activity and expression of GSTz1-1, which alters tyrosine metabolism and may cause hepatic and neurological toxicity [6].
• Inhibition of glutathione S-transferase zeta and tyrosine metabolism by dichloroacetate: a potential unifying mechanism for its altered biotransformation and toxicity [7].
• Pyruvate had a further beneficial effect on half of them; it was, however, inhibitory to some strains of M. malmoense, MAI and TBC as well as to BCG [8].

Biological context of GSTZ1

• A new allele of human GSTZ1, characterized by a Thr82Met substitution and termed GSTZ1d, has been identified by analysis of the expressed sequence tag (EST) database [9].
• Characterization and chromosome location of the gene GSTZ1 encoding the human Zeta class glutathione transferase and maleylacetoacetate isomerase [10].
• The FSD2 protein was identified from peptide mass data and best matched with the amino acid sequence of mouse and human Zeta 1 of glutathione S-transferase (GSTZ1) and showed a high GSTZ1 specific activity [11].
• METHODS: A total of 10 single-nucleotide polymorphisms (SNP) were identified in African and Australian European subjects in a region extending 1.5-kb upstream of the GSTZ1 start of transcription [2].
• The different amino acid substitutions have been mapped on to the recently determined crystal structure of GSTZ1-1 to evaluate and explain their influence on function [9].

Anatomical context of GSTZ1

• The minor FSD component (FSD2) is due to the GSTZ1 present in rat liver cytosol [11].
• Prediction of disease outcome with a linear combination of quantitative microscopical parameters of the primary tumor alone [MAI (mitotic activity index), DI and mean nuclear area] was very accurate, even without considering lymph-node status (MC 30.8, p less than 0.0005) [12].
• Pulmonary artery thrombosis and an anti-ethinyl-oestradiol monoclonal IgGlambda were found to be associated in a 36-year-old woman (Mrs MAI.) who took an oral contraceptive containing 50 mug ethinyl-oestradiol and 500 mug nor-ethisterone daily [13].
• The removal of erythrocyte sialic acid using neuraminidase to reduce surface negative charge led to unequivocal interference with aggregation (MAI technique of CHIEN et al., J. Gen. Physiol., 1973) by both anionic amphophiles were studied [14].
• At 3 MAI, glomerular lesions were characterized by focal segmental glomerulosclerosis showing segmental expansion of the mesangial area due to an increase of basement membrane-like material and mesangial cells with lipid droplets and foam cells [15].

Associations of GSTZ1 with chemical compounds

• The human zeta class glutathione transferase GSTZ1 has recently been characterized and analysis of expressed sequence tag clones suggested that this gene may be polymorphic [16].
• The coding region of the gene differed from the GSTZ1 cDNA at two nucleotide positions in exon 3, resulting in Lys-32-->Glu and Arg-42--> Gly substitutions [10].
• The evidence suggests that GSTZ1 may not be the major enzyme defluorinating fluoroacetate, but it does detoxify the fluoroacetate [17].
• Maleylacetoacetate isomerase (MAAI), a key enzyme in the metabolic degradation of phenylalanine and tyrosine, catalyzes the glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate [18].
• Here we report the crystal structure of human MAAI at 1.9 A resolution in complex with glutathione and a sulfate ion which mimics substrate binding [18].

Other interactions of GSTZ1

• Although low in comparison with other GSTs, GSTZ1-1 has glutathione peroxidase activity with t-butyl and cumene hydroperoxides [19].

Analytical, diagnostic and therapeutic context of GSTZ1

• Immunoblotting showed the presence of GSTZ in mouse, rat, and human liver cytosol [20].
• Recurrence-free survival was related independently to nuclear perimetry (P less than 0.001), SD of nuclear area (P = 0.01) and MAI (P = 0.019) in Cox's analysis [21].
• Axillary lymph node-negative (pN-) breast carcinomas (n = 281) were analysed histoquantitatively for two mitotic indexes (MAI, mitotic activity index; M/V, volume corrected mitotic index) and nine nuclear factors with special emphasis on disclosing prognostic factors during a follow-up of 12 years [21].
• The sequence analysis of genomic DNA for zeta class GST (GSTZ) locus in rice indicated that two homologous GSTZ genes lay in a tandem orientation with a short (0.4 kb) intergenic spacer [22].
• The reactivities of MAAI with HDL, ssDNA and dsDNA, phospholipids such as cardiolipin (CL), and coagulation factors were examined by ELISA [23].

References