Disease relevance of GDA

• Adenosine deaminase, 5'-nucleotidase, guanase and cytidine deaminase activities in gastric tissues from patients with gastric cancer [1].
• However, GDA levels in hepatitis A group were closed to the controls [2].
• In order to obtain insight into the aetiology and pathogenesis of amyotrophic lateral sclerosis (ALS), high-density gene discovery arrays (GDA human version 1.2) containing 18 400 non-redundant EST cDNAs pooled from different tissue libraries have been used to monitor gene expression in lumbar spinal cord from ALS cases compared with controls [3].
• Deficiency of guanine deaminase in human brain: a new brain disorder [4]?
• Serum guanase activity was measured by a new method and compared with serum glutamic oxalacetic transaminase and glutamic pyruvic transaminase levels in 150 patients with various disorders, 21 dogs with experimental myocardial infarction, and 2 CCl4-treated dogs [5].

Psychiatry related information on GDA

• Four spots containing transferrin, 14-3-3 alpha/beta and cypin, showed maximal protein expression levels at P30, thereby showing a positive correlation to critical period plasticity [6].

High impact information on GDA

• Neurons that express this mutant snRNA show little or no detectable cypin protein and fewer dendrites than normal [7].
• In addition, we found that cypin binds directly to tubulin heterodimers and promotes microtubule polymerization [7].
• Cypin is discretely expressed in neurons and is polarized to basal membranes in intestinal epithelial cells [8].
• 4. By regulating postsynaptic protein sorting, cypin may influence synaptic development and plasticity [8].
• However, serum guanase activity was normal in patients with a variety of non-liver-related diseases including acute myocardial infarction, and in dogs with experimental myocardial infarction without liver damage, even when the serum glutamic oxalacetic transaminase and glutamic pyruvic transaminase activities were increased [5].

Chemical compound and disease context of GDA

• Selective cytotoxicity of L-glutamic acid gamma-monohydroxamate (GAH) for melanoma tumor cells [9].
• A deficiency of xanthine oxidase, guanine deaminase and guanosine kinase activities was found in neuroblastoma cells [10].
• Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody GAH, in colorectal cancer xenografts [11].

Biological context of GDA

• Cloning and characterization of human guanine deaminase. Purification and partial amino acid sequence of the mouse protein [12].
• These findings suggest that alternative splicing of nedasin may play a role in the formation and/or structural change in synapses during neuronal development by modifying clustering of neurotransmitter receptors at the synaptic sites [13].
• Furthermore, there were correlations between GAH levels and BMI, and between GAH and blood pressure [14].
• Cell cycle analysis of tumor and normal cells treated with GAH (18 hrs, 1,2 mM) has shown that the drug prevents both cell type from cycling from G1 to S phase [9].
• A longer exposure time to GAH (18 hrs) and an additional 54 hrs of culture after removal of GAH led to 50 +/- 10% of cell survival with normal cells but only 25 +/- 10% with tumor cells [9].

Anatomical context of GDA

• Guanase activity was observed uniformly in the rat hepatocytes, biliary epithelium and vascular endothelium cells, while it was localized to the hepatocytes and biliary epithelium in the human liver [15].
• As predicted, inhibition of guanase, which metabolizes guanine and hypoxanthine to xanthine, caused a marked inhibition of binding in the cerebral cortex and midbrain, where there is an abundance of enzyme, and only slight change in binding in the medulla, cerebellum or pons, where there is little enzyme [16].
• The hemodynamics of the GDA were revealed noninvasively using Doppler ultrasonography in a patient with a malignant islet cell tumor of the pancreas and one with a ductal cell carcinoma of the pancreas [17].
• Fifty-six of the patients received intraoperative implantation through the gastroduodenal artery (GDA catheterization), 31 received external catheterization (EXT catheterization) and 22 received catheterization using a saphenous vein graft (SVG catheterization) [18].
• Similar effects were seen with the pretreatment of T cells with an irrelevant negative control primary mAb or a secondary-step goat anti-mouse immunoglobulin (GAM Ig), goat anti-human IgM-Fc (GAH Fc mu), or both [19].

Associations of GDA with chemical compounds

• The human coding sequence of the putative enzyme was subcloned into the bacterial expression vector pMAL-c2, expressed, purified, and characterized as having guanine deaminase activity with a Km for guanine of 9.5 +/- 1.7 microM [12].
• In tissue sections, the immunohistochemical reaction with this antibody was positive in the same locations as the histochemical guanase reaction with DAB (3,3'-diaminobenzidine tetrahydrochloride) [20].
• Isocitrate dehydrogenase, guanase and glutamate dehydrogenase alone were poor discriminants of the various disease categories studied; combination of the latter enzyme with the aminotransferases in various ratios did not achieve worthwhile improvement [21].
• Xanthine oxidase, guanase, 5'-nucleotidase, and adenosine deaminase in human epidermis were demonstrated and accurately assayed with about 20 microng. of tissue by the new micro-assay methods which rely on the isolation of isotopically labeled end products from the substrates by electrophoresis on cellulose acetate membranes [22].
• It was also noted that the infection modified the enzymatic activities of this purine salvage pathway, in particular, the guanine deaminase cerebral activity of infected mice was 20-fold lower than the value of controls [23].

Physical interactions of GDA

• NE-dlg/SAP102 is shown to interact with only the S form of nedasin which is predominantly expressed in brain [13].

Co-localisations of GDA

• The expression of nedasin in neuronal cells increases in parallel with the progress of synaptogenesis and is mainly detected in cell bodies where it co-localizes with NE-dlg/SAP102 [13].

Other interactions of GDA

• Activities of adenosine deaminase, 5'-nucleotidase, guanase, and cytidine deaminase enzymes in cancerous and non-cancerous human breast tissues [24].
• GUA/CD ratios were however lower and the other ratios higher in the cancerous tissues [24].
• It has been suggested that increased ADA and 5'NT together with decreased GUA activities might be a physiologic attempt of the cancer cells to provide more substrates needed by cancer cells to accelerate the salvage pathway activity [24].
• Here we report the isolation of a novel NE-dlg/SAP102-associated protein, p51-nedasin [13].
• Binding of cypin to PSD-95 correlates with formation of stable dendrite branches [25].

Analytical, diagnostic and therapeutic context of GDA

• Affinity chromatography identifies cypin as a major PSD-95-binding protein in brain extracts [8].
• An immunoblotting study showed that the antibody bound specifically to one band of protein with guanase activity and not to other proteins [20].
• To test the above theory, the binding of 3H-flunitrazepam to receptors was studied on homogenates of various regions of autopsied human brain before and after treatment with irreversible potent inhibitors of the purine enzymes guanine deaminase and adenosine deaminase [16].
• GDA catheterization was no better than the other two procedures and it had a higher incidence of complications and a lower patency [18].
• The relation between efficacy and antigen density was examined on 10 xenograft models bearing cancer cells with varying GAH reactivity [26].

References