Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most chromosome aberrations in gliomas are numerical, resulting in either gains or deficiencies of whole chromosomes. In tumors of low malignancy, the karyotype is frequently normal or exhibits a loss of sex chromosome and a gain of chromosome 7. These two anomalies may not be directly related to malignancy. In the highly malignant cases, the two most frequent aberrations are the gain of chromosome 7 and the loss of chromosome 10, other anomalies such as losses or deletions of chromosomes, 9, 22, 6, 13 and 14 being detected at various frequencies. Several of these chromosomes carry important genes of adenine metabolism: AK1 and AK3 (adenylate kinase) and MTAP (methylthioadenosine phosphorylase) for chromosome 9; ADK (adenosine kinase) and mitochondrial ATPase for chromosome 10; ADSL (adenylosuccinate lyase) for chromosome 22, NP (nucleoside phosphorylase) for chromosome 14. We performed the corresponding assays of enzyme activity on both fresh tumors and tumors grafted on nude mice, which showed that these enzymes had a relatively low activity although the tumors were proliferating. However, chromosome losses do not seem to directly cause the metabolic alterations by gene dosage effect. Interestingly, chromosome 10, frequently deficient, also carries genes of importance for glycolysis (hexokinase) and glutamate metabolism (glutamate dehydrogenase and glutamate oxaloacetate transaminase). The deficiency for these genes could be taken into account for a better type of chemotherapy by antimetabolics.
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PMID:[Chromosome abnormalities and adenine metabolism in human glial tumors]. 144 60

Reactive analogs of substrates or allosteric regulators can be designed to bind reversibly to particular ligand sites of enzymes. Subsequently, these compounds can react covalently with amino acids accessible from the ligand site, thereby functioning as chemical arrows aimed at specific enzymatic target sites. The approach of affinity labeling can be used to identify amino acid participants in active or regulatory sites, to provide a rational choice of targets for site-directed mutagenesis experiments, or to monitor conformational changes in the region of a particular enzyme site. Illustrations of these approaches include: 1) the use of reactive nucleotide analogs directed to substrate sites in adenylosuccinate synthetase and adenylosuccinate lyase and to regulatory sites of glutamate dehydrogenase, 2) the use of affinity cleavage by Fe2(+)-isocitrate to locate the metal-substrate site of isocitrate dehydrogenase, and 3) the use of reactive peptides and aromatic compounds to target the glutathione and xenobiotic sites of glutathione S-transferases.
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PMID:Chemical arrows for enzymatic targets. 906 10