Disease relevance of GLYOXALASE I

• HLA, complement, and glyoxalase I alleles were studied in 29 families in which at least one member has classical 21-hydroxylase-deficiency congenital adrenal hyperplasia [1].
• Characterization of recombinant L. major glyoxalase I showed it to be unique among the eukaryotic enzymes in sharing the dependence of the E. coli enzyme on nickel [2].
• They suggest a previously unidentified role for glyoxalase I in neurodegenerative disease [3].
• Human glyoxalase I. cDNA cloning, expression, and sequence similarity to glyoxalase I from Pseudomonas putida [4].
• Among the many highlights of nickel metallobiochemistry in 1998 were the discoveries that Escherichia coli glyoxalase I is the first example of a nickel isomerase, and that the superoxide dismutase isolated from Streptomyces seoulensis is a new structural class of superoxide dismutase that features thiolate ligation [5].

Psychiatry related information on GLYOXALASE I

• Role for glyoxalase I in Alzheimer's disease [3].
• Association analysis of the functional Ala111Glu polymorphism of the glyoxalase I gene in panic disorder [6].
• The zinc metalloenzyme glyoxalase I (GLO1) is thought to play a role in anxiety disorders because a reduced brain expression of GLO1 has been associated with increased anxiety-behaviours in mice [6].

High impact information on GLYOXALASE I

• Two electrophoretically distinct variants of glyoxalase I (Glo-I) are present in mouse (Mus musculus) [7].
• Glyoxalase I polymorphism in the mouse: a new genetic marker linked to H-2 [7].
• Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis [8].
• Overexpression of glyoxalase-I completely prevented both hyperglycemia-induced AGE formation and increased macromolecular endocytosis [8].
• The haplotype containing this rare set of complement alleles always carried the rare HLA allele, HLA-Bw47, usually carried HLA-A3, and almost always had the alleles HLA-Cw6, HLA-DR7, and the glyoxalase I (GLO) allele GLO1 [1].

Chemical compound and disease context of GLYOXALASE I

• Increased levels of methylglyoxal-metabolizing enzymes in mononuclear and polymorphonuclear cells from insulin-dependent diabetic patients with diabetic complications: aldose reductase, glyoxalase I, and glyoxalase II--a clinical research center study [9].
• The glyoxalase I mutants were expressed in Escherichia coli and purified on an S-hexylglutathione affinity gel [10].
• The DNA and deduced amino acid sequence of the second ORF of clone C1 showed significant homology to gloA, encoding glyoxalase I enzyme, of Salmonella typhimurium and Escherichia coli [11].
• Diethyl esters of the glutathione S-conjugate S-p-bromobenzylglutathione, an inhibitor of glyoxalase I, and S-p-nitrobenzoxycarbonylglutathione, an inhibitor of glyoxalase II, induced growth arrest and toxicity in human leukaemia 60 cells in culture [12].
• A possible regulatory role of 17beta-estradiol and tamoxifen on glyoxalase I and glyoxalase II genes expression in MCF7 and BT20 human breast cancer cells [13].

Biological context of GLYOXALASE I

• In the course of family studies of haplotypes of the alleles of the sixth chromosome loci HLA-A, C, B, D/DR, BF, C2, C4A, C4B, and glyoxalase I, we encountered an unusual BF variant [14].
• Here we report that TNF induces an increased phosphorylation of glyoxalase I that is mediated by protein kinase A and required for cell death [15].
• This trypanothione-dependent glyoxalase I is therefore an attractive focus for additional biochemical and genetic investigation as a possible target for rational drug design [2].
• Glyoxalase I is involved in resistance of human leukemia cells to antitumor agent-induced apoptosis [16].
• Here we show that the Yap1 transcription factor, which is critical for the oxidative-stress response in Saccharomyces cerevisiae, is constitutively concentrated in the nucleus and activates the expression of its target genes in a glyoxalase I-deficient mutant [17].

Anatomical context of GLYOXALASE I

• A new variant glyoxalase I allele that is readily detectable in stimulated lymphocytes and lymphoblastoid cell lines but not in circulating lymphocytes or erythrocytes [18].
• The cell line was heterozygous at the glyoxalase I locus and had the HLA haplotypes HLA-A1, B8, DRw3, and HLA-A2, B5, DRw1 [19].
• Our findings indicate that glyoxalase I is critical for pericyte survival under hyperglycemic conditions, and its inactivation and/or down-regulation by NO. may contribute to pericyte death by apoptosis during the early stages of diabetic retinopathy [20].
• Transfection of COS-1 cells with the 622-base pair cDNA containing the entire coding region cloned into a pMT2 vector produced an immunoreactive protein and an approximate 180-fold increase in glyoxalase-I enzyme activity as determined with methylglyoxal as a substrate [21].
• We investigated the effects of glutathione-S-transferase (GST) inhibitor treatment on human colon HT29 cell mRNA levels of dihydrodiol dehydrogenase (DDH), glyoxalase I, and gamma-glutamylcysteine synthetase [22].

Associations of GLYOXALASE I with other chemical compounds

• The enzyme is distinct from the glutathione S-transferases, mercaptopyruvate sulfurtransferase, and glyoxalase I. Substrate specificity studies showed that S-phenacylglutathiones are the preferred first substrates and that several thiols (glutathione, mercaptoethanol, L-cysteine, or cysteamine) serve as reducing substrates [23].
• Pharmacological scavenging of methylglyoxal prevented anoikis and maintained angiogenesis, and inhibition of methylglyoxal metabolism with a cell permeable glyoxalase I inhibitor provoked these responses in normoglycemia [24].
• We have investigated the role of MGO and its metabolizing enzyme, glyoxalase I, in high glucose-induced apoptosis (annexin V binding) of human retinal pericyte (HRP) [20].
• The conformational mobility of glyoxalase I (Glx I) during catalysis has been probed using stable analogs of the enediol intermediate that forms along the reaction pathway: GSC(O)N(OH)R, where GS = glutathionyl and R = CH3 (1), C6H5 (2), C6H4Cl (3), or C6H4Br (4) [25].
• While the partition ratio (fluoride eliminated/total fluoride) was insensitive to pH 5.5-7.5 and concentrations of substrate and glyoxalase I, it was species-dependent [26].

Gene context of GLYOXALASE I

• The structural gene for glyoxalase I (GLO1) of Saccharomyces cerevisiae was identified [27].
• PURPOSE: Glyoxalase I (GLO1) is an enzyme that plays a role in the detoxification of methylglyoxal, a side-product of glycolysis [28].
• A correlation between the expression or absence of human glyoxalase I and chromosome 6 (as well its markers ME1, IPO-B, and PGM3) was observed in man-mouse somatic cell hybrids [29].
• The locus for glyoxalase i (GLO) is between HLA-A and PGM3 on chromosome 6 of man [30].
• Growth studies showed that the most sensitive strains to 2-oxoaldehydes were the null mutants for GSH1 and GLO1, coding for glutathione synthase I and glyoxalase I respectively [31].

Analytical, diagnostic and therapeutic context of GLYOXALASE I

• However, levels of glyoxalase I protein were significantly elevated in P301L brains, as shown by Western blot analysis and immunohistochemistry [3].
• In situ hybridization analysis revealed expression of glyoxalase I in all brain areas analyzed, both in transgenic and control mice [3].
• Database mining and sequence analysis identified putative glyoxalase I genes in the eukaryotic human parasites Leishmania major, Leishmania infantum, and Trypanosoma cruzi, with highest similarity to the cyanobacterial enzymes [2].
• The tertiary structure of the monomeric yeast glyoxalase I has been modeled based on the crystal structure of the dimeric human glyoxalase I and a sequence alignment of the two enzymes [32].
• Examination of colon carcinomas for the amplification of the glyoxalase-I gene by Southern blot analysis revealed no change in gene copy number [21].

References