Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The metabolism of extracellular nucleotides in NG108-15 cells, a neuroblastoma x glioma hybrid cell line, was studied by means of capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MECC). 2. In NG108-15 cells ATP, ADP, AMP, UTP, UDP, and UMP were hydrolyzed to the nucleosides adenosine and uridine indicating the presence of ecto-nucleotidases and ectophosphatases. The hydrolysis of the purine nucleotides ATP and ADP was significantly faster than the hydrolysis of the pyrimidine nucleotides UTP and UDP. 3. ATP and UTP breakdown appeared to be mainly due to an ecto-nucleotide-diphosphohydrolase. ADP, but not UDP, was initially also phosphorylated to some extent to the corresponding triphosphate, indicating the presence of an adenylate kinase on NG108-15 cells. The alkaline phosphatase (ALP) inhibitor levamisole did not only inhibit the hydrolysis of AMP to adenosine and of UMP to uridine, but also the degradation of ADP and to a larger extent that of UDP. ATP and UTP degradation was only slightly inhibited by levamisole. 4. These results underscore the important role of ecto-alkaline phosphatase in the metabolism of adenine as well as uracil nucleotides in NG108-15 cells Dipyridamole, a potent inhibitor of nucleotide breakdown in superior cervical ganglion cells, had no effect on nucleotide degradation in NG108-15 cells. 5. Dipyridamole, which is a therapeutically used nucleoside reuptake inhibitor in humans, reduced the extracellular adenosine accumulation possibly by allosteric enhancement of adenosine reuptake into the cells.
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PMID:Extracellular metabolism of nucleotides in neuroblastoma x glioma NG108-15 cells determined by capillary electrophoresis. 1282 32

Altered cellular bioenergetics and mitochondrial function are major features of several diseases, including cancer, diabetes, and neurodegenerative disorders. Given this important link to human health, we sought to define proteins within mitochondria that are critical for maintaining homeostatic ATP levels. We screened an RNAi library targeting >1,000 nuclear-encoded genes whose protein products localize to the mitochondria in multiple metabolic conditions in order to examine their effects on cellular ATP levels. We identified a mechanism by which electron transport chain (ETC) perturbation under glycolytic conditions increased ATP production through enhanced glycolytic flux, thereby highlighting the cellular potential for metabolic plasticity. Additionally, we identified a mitochondrial adenylate kinase (AK4) that regulates cellular ATP levels and AMPK signaling and whose expression significantly correlates with glioma patient survival. This study maps the bioenergetic landscape of >1,000 mitochondrial proteins in the context of varied metabolic substrates and begins to link key metabolic genes with clinical outcome.
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PMID:A mitochondrial RNAi screen defines cellular bioenergetic determinants and identifies an adenylate kinase as a key regulator of ATP levels. 2481 68

Adenylate kinase is a small, usually monomeric, enzyme found in every living thing due to its crucial role in energetic metabolism. This paper outlines the most relevant data about adenylate kinases isoforms, and the connection between dysregulation or mutation of human adenylate kinase and medical conditions. The following datadases were consulted: National Centre for Biotechnology Information, Protein Data Bank, and Mouse Genomic Informatics. The SmartBLAST tool, EMBOSS Needle Program, and Clustal Omega Program were used to analyze the best protein match, and to perform pairwise sequence alignment and multiple sequence alignment. Human adenylate kinase genes are located on different chromosomes, six of them being on the chromosomes 1 and 9. The adenylate kinases' intracellular localization and organ distribution explain their dysregulation in many diseases. The cytosolic isoenzyme 1 and the mitochondrial isoenzyme 2 are the main adenylate kinases that are integrated in the vast network of inflammatory modulators. The cytosolic isoenzyme 5 is correlated with limbic encephalitis and Leu673Pro mutation of the isoenzyme 7 leads to primary male infertility due to impairment of the ciliary function. The impairment of the mitochondrial isoenzymes 2 and 4 is demonstrated in neuroblastoma or glioma. The adenylate kinases are disease modifier that can assess the risk of diseases where oxidative stress plays a crucial role in pathogenesis like metabolic syndrome or neurodegenerative diseases. Because adenylate kinases has ATP as substrate, they are integrated in the global network of energetic process of any organism therefore are valid target for new pharmaceutical compounds.
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PMID:Adenylate Kinase: A Ubiquitous Enzyme Correlated with Medical Conditions. 3066 86