Nucleoside diphosphate kinase (Ndk) is ubiquitous and highly conserved multifunctional key enzyme in nucleotide metabolism. It generates nucleoside triphosphates (NTPs) by transfer of gamma-phosphates from nucleoside triphosphates such as ATP or GTP to nucleoside diphosphate. The formation of an autophosphorylated enzyme intermediate is involved in that mechanism. The phosphate is usually supplied by ATP and Ndk activity in different subcellular compartments. Ndk may regulate the crucial balance between ATP and GTP or other nucleoside triphosphates. Ndk is playing an important role in bacterial pathogenesis and emerging evidences recognize multiple roles of Ndk in host-microbe interaction. Here, I review some examples of the role of Ndk in intra- and extracellular microorganism.
Adenosine Triphosphate ; Guanosine Triphosphate ; Nucleoside-Diphosphate Kinase

OBJECTIVES: We investigated the effects of the economic growth and unemployment rates on the suicide rate in Korea, between 1983 and 2000, using a time-series regression model. The purpose of this study was to model and test the magnitude of the rate of suicide, with the Korean unemployment rate and GDP. METHODS: Using suicide rate per 100, 000 Koreans and the unemployment rates between 1983 and 2000, as published by the Korea National Statistical Office, and the rate of fluctuation of the Korean GDP (Gross Domestic Product), as provided by the Bank of Korea, as an index of the economic growth rate, a time-series regression analysis, with a first-order autoregressive regression model, was performed. RESULTS: An 81.5% of the variability in the suicide rate was explained by GDP, and 82.6% of that was explained by the unemployment rate. It was also observed that the GDP negatively correlated with the suicide rate, while the unemployment and suicide rates were positively correlated. For subjects aged over 20, both the GDP and unemployment rate were found to be a significant factors in explaining suicide rates, with coefficients of determination of 86.5 and 87.9%, respectively. For subjects aged under 20, however, only the GDP was found to be a significant factor in explaning suicide rates (the coeficient of determination is 38.4%). CONCLUSION: It was found that the suicide rate was closely related to the National's economic status of Korea, which is similar to the results found in studies in other countries. We expected, therefore, that this study could be used as the basis for further suicide-related studies.
Economic Development* ; Guanosine Diphosphate ; Korea* ; Suicide* ; Unemployment*

No abstract available.
Carrier Proteins ; Guanosine Triphosphate ; Signal Transduction

Taking the typical metabolic control product-guanosine as an example, the method of metabolic flux shift investigation based on process multi-levels parameter correlation analysis was established. The metabolic pathway, multi-parameter correlation, accumulation of amino acid and organic acid during guanosine fermentation process were integratively analyzed. The metabolic flux shift from HMP to EMP was ascertained, which was assumed to be caused by the accumulation of ammonium ion. The subsequent optimization based on controlling flux distribution between EMP and HMP did improve the yield by 35% when the metabolic flux shift was prevented.
Amino Acids ; metabolism ; Ammonia ; metabolism ; Fermentation ; Guanosine ; metabolism

The dried fruit body of Phylloporia ribis(Hymenochaetaceae), which prefers to live on the stumps of Lonicera japonica(Caprifoliaceae), has a variety of activities, whereas its pharmacodynamic material basis is not completely clear and there are few reports on its quality control and evaluation. In this study, an UPLC-Q-TOF-MS method was used to analyze the nucleosides and nucleobases in P. ribis and a HPLC method was established for simultaneous determination of 10 nucleosides and nucleobases. MS and MS/MS data were acquired in positive ion mode. Based on the data comparison of the sample and the reference substance, the literature data and the compound databases of ChemSpider and PubChem, 18 nucleosides and nucleobases were identified qualitatively from the water extract of P. ribis for the first time. After optimization, the HPLC was performed using a Welch Ultimate AQ C_(18) column(4.6 mm×250 mm, 5 μm) by gradient elution with acetonitrile and water as mobile phase, the flow rate of 1.0 mL·min~(-1), the detection wavelength of 260 nm, and the column temperature of 30 ℃. Through the investigation of the extraction method, solvent and time, it was determined that the test solution should be obtained by cold water extraction for 18 h. At the present HPLC conditions, 10 components of uracil, cytidine, hypoxanthine, uridine, thymine, inosine, guanosine, 2'-deoxyinosine, 2'-deoxyguanosine and thymidine could be well separated(R > 1.5) and showed good linearity(r > 0.999 9) in the concentration ranges of 0.247-24.7, 0.283-28.3, 0.273-27.3, 0.256-25.6, 0.257-25.7, 0.318-31.8, 0.245-24.5, 0.267-26.7, 0.250-25.0 and 0.267-26.7 mg·L~(-1), respectively. The average reco-veries of 10 components were 95.78%-104.5%, and the RSDs were 2.2%-5.2%(n=6). The contents of 10 nucleosides and nucleobases in different samples of P. ribis varied greatly, which were 0.021-0.122, 0.004-0.029, 0.014-0.226, 0.009-0.442, 0.003-0.014, 0.002-0.146, 0.007-0.098, 0-0.054, 0.005-0.069, 0.004-0.081 and 0.072-1.28 mg·g~(-1) for uracil, cytidine, hypoxanthine, uridine, thymine, inosine, guanosine, 2'-deoxyinosine, 2'-deoxyguanosine, thymidine and total 10 components, respectively. These results demonstrated that the components had significant differences in the internal quality, and good quality control was needed to ensure the medical efficacy. This study provides a scientific basis for the discovery of pharmacodynamic ingredients, quality control and evaluation of P. ribis.
Basidiomycota ; Chromatography, High Pressure Liquid ; Guanosine ; Nucleosides ; Tandem Mass Spectrometry

RalA GTPase, a member of Ras superfamily proteins, shows alternative forms between the active GTP-binding and the inactive GDP-binding states. Ral-specific guanine nucleotide exchange factor such as RalGDS interacts with activated Ras and cooperates with Ras indicating that Ral can be activated through Ras signaling pathway. Another activation path for Ral are through Ca2+-dependent but Ras-independent manner. In this study, studies were carried out to examine possible effects of Ca2+ and calmodulin, Ca2+-binding protein, directly on the GTP/GDP-binding state to recombinant unprenylated GST-RalA proteins. The results showed that Ca2+ stimulated the binding of GTP to RalA, whereas it reduced the binding of GDP to RalA. However, it does not involve a high affinity association of Ca2+ with RalA. Ca2+/calmodulin stimulated the GTPase activity of RalA. These results indicate that Ca2+ alone activates RalA by stimulating GTP-binding to RalA and Ca2+/calmodulin inactivates RalA by increasing the activity of RalGTPase.
Animal ; Brain/metabolism ; Calcium/*metabolism ; Calmodulin/*metabolism ; GTP Phosphohydrolases/*metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/*metabolism ; Rats ; Support, Non-U.S. Gov't ; Synaptosomes/metabolism

G protein-coupled receptors (GPCRs) are membrane receptors; approximately 40% of drugs on the market target GPCRs. A precise understanding of the activation mechanism of GPCRs would facilitate the development of more effective and less toxic drugs. Heterotrimeric G proteins are important molecular switches in GPCR-mediated signal transduction. An agonist-activated receptor interacts with specific sites on G proteins and promotes the release of GDP from the Galpha subunit. Because of the important biological role of the GPCR-G protein coupling, conformational changes in the G protein upon receptor coupling have been of great interest. One of the most important questions was the interface between the GPCR and G proteins and the structural mechanism of GPCR-induced G protein activation. A number of biochemical and biophysical studies have been performed since the late 80s to address these questions; there was a significant breakthrough in 2011 when the crystal structure of a GPCR-G protein complex was solved. This review discusses the structural aspects of GPCR-G protein coupling by comparing the results of previous biochemical and biophysical studies to the GPCR-G protein crystal structure.
GTP-Binding Proteins ; Guanosine Diphosphate ; Heterotrimeric GTP-Binding Proteins ; Membranes ; Signal Transduction

OBJECTIVE: Volume expansion has been known to be the major factor in the development of hypertenision in chronic hemodialysis(HD) patients. But some HD patients remain hypertensive even with adequate volume control, which suggests the role of undefined uremic toxin in the pathogenesis of hypertension. So we aimed to evaluate the status of blood pressure (BP) control and the effect of Kt/V (as a marker for removal of uremic toxin) on BP in chronic HD patients. METHODS: The status of BP control was obtained from records of 8 HD session in 132 patients in November 1996 and 127 patients in November 1997. Of 132 patients studied in 1996, 70 patients underwent a follow-up evaluation in 1997. All patients were dialyzed 3 times a week, 4 hours a session. Postdialytic cyclic 3',5' guanosine monophosphate (cGMP) level was measured in 48 patients as a marker of volume status. RESULTS: The prevalence of postdialytic hypertension (>140/90mmHg) was 73.5 in 1996 and 65.3% in 1997. Normotensive patients (postdialytic mean BP<114 mmHg) had higher Kt/V value than hypertensive patients in both 1996 and 1997. But there was no difference in the degree of ultrafiltration (UF) and cGMP level between two groups. Postdialytic mean BP was inversely correlated with Kt/V level but had no relationship with degree of UF and cGMP level in both 1996 and 1997. The group in which postdialytic mean BP had been decreased during 1 year study period had higher degree of elevation in Kt/V than the group in which postdialytic mean BP had been increased. The changes of postdialytic weight and degree of UF during study period were similar between two groups. The number of antihypertensives used were also inversely correlated with Kt/V but not correlated with degree of UF and cGMP level in both 1996 and 1997. CONCLUSION: Our study indicate that increasing HD adequacy is associated with improved control of postdialytic mean BP and less use of antihypertensive drugs. UF and antihypertensive drugs may not be adequate form of hypertension treatment as once thought and increasing HD adequacy can be an alternative method.
Antihypertensive Agents ; Blood Pressure* ; Dialysis* ; Follow-Up Studies ; Guanosine Monophosphate ; Humans ; Hypertension ; Prevalence ; Renal Dialysis* ; Ultrafiltration

BACKGROUND: We reported the beneficial effect of low GDP solution on rapid remesothelialization and less EMT in the peritoneum with time on CAPD. In a prospective study, we investigated the effect of switching solution from high GDP to low GDP on the restoration of EMT from human peritoneal mesothelial cells (HPMCs) in CAPD patients via ex vivo. METHODS: 21 patients (11 females, DM:11, mean age: 52.1+/-13.4 years old) who had used high GDP solution (pH 5.5, stay-safe(R), FMC) for more than 1 year (mean 14+/-6.4 months) were treated with the low GDPs solution (pH 7.0, stay-safe Balance(R), FMC) at least additional 12 months. Drained HPMCs from overnight effluent were cultured on T25 flask at the 6 months before switching to low GDPs solution (Time -6), just before switching (Time 0), 3 months after switching (Time +3), 6 months after switching (Time +6) and 12 months after switching (Time +12). When they had nearly reached to confluence, cell scores were blindly measured by the same person (Score 1: cobble stone shaped HPMCs, Score 2: mixed, Score 3:fibroblast dominant). Cell scores and clinical indices were compared between Time 0 and the others. We analyzed data with paired t-test. RESULTS: Cell score was a significantly lower at Time -6 than Time 0 (1.63+/-0.8 vs. 2.06+/-0.85, p= 0.014). But, there was no difference of level of D-CA125 between two groups (23.4+/-13.0 vs. 23.7+/-13.4 (IU/mL), p=N.S., N=16). There was no difference of cell scores between Time +3 and Time 0 (2.24+/-0.94 vs. 2.19+/-0.87, p=N.S., N=21). There were significantly lower cell score (1.71+/-0.90 vs. 2.19+/-0.87, p=0.038) and significantly higher level of D-CA125 (37.4+/-20.3 vs. 24.4+/-13.4 (IU/mL), p=0.004) at Time +6 than Time 0 (N=17). There were significantly lower cell score (1.60+/-0.88 vs. 2.20+/-0.89, p=0.014) and significantly higher level of D-CA125 (46.2+/-20.9 vs. 20.1+/-11.5 (IU/mL), p=0.000) in Time +12 than Time 0 (N=17). CONCLUSION: Our study suggests that, although restoration of EMT took some time, the switching into GDP solution from conventional solution might be helpful to pre-Jong-Won Park, et al.: Restoration of Epithelial to Mesenchymal Transition in CAPD Patients-serve the peritoneal membrane with time on PD.
Dialysis* ; Female ; Glucose* ; Guanosine Diphosphate* ; Humans ; Membranes ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory* ; Peritoneum ; Prospective Studies

Photoaffinity labeling is widely applied to demonstrate targets of small molecule ligands. In this paper, biotin photoaffinity labeled molecule with propargyl group 1 has been designed and synthesized, followed it's labeling of N2-acetyl-2'-O-propargyl guanosine 9 by "click chemistry". This technology presents delight development potential in labeling of second messenger cyclic nucleotide, antisense oligonucleotide or siRNA.
Biotin ; chemistry ; Click Chemistry ; Guanosine ; chemical synthesis ; chemistry ; Ligands ; Photoaffinity Labels