Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extent to which sugars serve as targets for superoxide was examined using glycolaldehyde as the simplest sugar and using superoxide dismutase (SOD)-replete and SOD-null strains growing under aerobic and anaerobic conditions. Glycolaldehyde was more toxic to the SOD-null strain than to its SOD-replete parent, and this differential effect was oxygen-dependent. The product, glyoxal, could be trapped in the medium by 1,2-diaminobenzene and assayed as quinoxaline. The SOD-null strain produced more glyoxal and eliminated it more slowly than the SOD-replete parent strain. Glyoxal was approximately 10 times more toxic than glycolaldehyde and was more toxic to the SOD-null strain than to the parental strain. 1,2-Diaminobenzene protected against the toxicity of glycolaldehyde. These Escherichia coli strains contained the glutathione-dependent glyoxalases I and II, as well as the glutathione-independent glyoxalase III. Of these enzymes, glyoxalase III was most abundant, and it was inactivated within the aerobic SOD-null strain and also in extracts when exposed to the flux of superoxide and hydrogen peroxide imposed by the xanthine oxidase reaction. Thus, it appears that short chain sugars are oxidized by superoxide yielding toxic dicarbonyls. Moreover, the defensive glyoxalase III is also inactivated by the oxidative stress imposed by the lack of SOD, thereby exacerbating the deleterious effect of sugar oxidation.
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PMID:The role of alpha,beta -dicarbonyl compounds in the toxicity of short chain sugars. 1093 45

Glyoxal, methylglyoxal and other physiological alpha-oxoaldehydes are formed by the lipid peroxidation, glycation and degradation of glycolytic intermediates. They are detoxified enzymically by the glyoxalase system. To investigate the physiological function of glyoxalase I in parasitic organisms, the cDNA for glyoxalase I from the filarial nematode Onchocerca volvulus (designated Ov-GloI) has been cloned and characterized. The isolated cDNA contains an open reading frame of 579 bp encoding a protein with a calculated molecular mass of 21930 Da. Owing to the high degree of sequence identity (60%) with human glyoxalase I, for which the X-ray structure is available, it has been possible to build a three-dimensional model of Ov-GloI. The modelled core of Ov-GloI is conserved compared with the human glyoxalase I; however, there are critical differences in the residues lining the hydrophobic substrate-binding pocket of Ov-GloI. A 22 kDa protein was obtained by heterologous expression in Escherichia coli. A homogeneous enzyme preparation was obtained by affinity purification and functional characterization of the recombinant enzyme included the determination of kinetic constants for methylglyoxal and phenylglyoxal as well as inhibition studies. Gel filtration demonstrated a dimeric structure. To assess the role of Ov-GloI as a potential vaccine candidate or serodiagnostic tool, the serological reactivity of the recombinant Ov-GloI was analysed with sera from microfilaria carriers and specific IgG1 antibodies were detected. The effects of oxidative insult, namely plumbagin and xanthine/xanthine oxidase, on the gene transcript level of Ov-GloI were investigated. By using a semi-quantitative PCR ELISA it was shown that Ov-GloI is expressed at elevated levels under conditions of oxidative stress.
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PMID:A stress-responsive glyoxalase I from the parasitic nematode Onchocerca volvulus. 1117 Oct 39