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Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism.

Aughey GN, Grice SJ, Shen QJ, Xu Y, Chang CC, Azzam G, Wang PY, Freeman-Mills L, Pai LM, Sung LY, Yan J, Liu JL - Biol Open (2014)

Bottom Line: Furthermore, our global metabolic profiling demonstrates that CTPsyn overexpression does not significantly alter CTPsyn-related enzymatic activity, suggesting that cytoophidium formation facilitates metabolic stabilisation.In addition, we show that overexpression of CTPsyn only results in moderate increase of CTP pool in human stable cell lines.Together, our study provides experimental evidence, and a mathematical model, for the hypothesis that inactive CTPsyn is incorporated into cytoophidia.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom.

No MeSH data available.


Related in: MedlinePlus

Global metabolomic profiling indicates negligible changes in CTPsyn activity in vivo.(A) Principle component analysis shows that the samples of wild-type (Wt), CTPsyn inhibition (In), and CTPsyn overexpression (Oe) groups are clearly segregated. Two principal components (PC1 and PC2) are plotted and their proportions of variance are labeled. (B) The mean values of compounds in each state were normalized to (−1,1) and clustered into nine patterns by self-organizing mapping. The numbers of compounds in each pattern are showed on the top of the grids. The patterns that contain the most compounds are indicated by (I, II, III, V). (C) The heat map shows metabolites in major patterns that have significantly differential levels in three groups. Seventy-two metabolites in major patterns of (B) SOM (I, II, III, IV) were selected by one-way ANOVA with Bonferroni adjusted P<10−5. (D) The levels of glutamine in three groups are shown in the boxplot. Glutamine belongs to pattern I and is also colored in red in panel C.
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f05: Global metabolomic profiling indicates negligible changes in CTPsyn activity in vivo.(A) Principle component analysis shows that the samples of wild-type (Wt), CTPsyn inhibition (In), and CTPsyn overexpression (Oe) groups are clearly segregated. Two principal components (PC1 and PC2) are plotted and their proportions of variance are labeled. (B) The mean values of compounds in each state were normalized to (−1,1) and clustered into nine patterns by self-organizing mapping. The numbers of compounds in each pattern are showed on the top of the grids. The patterns that contain the most compounds are indicated by (I, II, III, V). (C) The heat map shows metabolites in major patterns that have significantly differential levels in three groups. Seventy-two metabolites in major patterns of (B) SOM (I, II, III, IV) were selected by one-way ANOVA with Bonferroni adjusted P<10−5. (D) The levels of glutamine in three groups are shown in the boxplot. Glutamine belongs to pattern I and is also colored in red in panel C.

Mentions: Principle component analysis of metabolome data showed that the three groups are clearly distinct from each other in terms of their global metabolite levels (Fig. 5A). We then used a self-organizing map (SOM) to reveal the relative metabolite changes among the three groups for all metabolites. As shown in Fig. 5B, four major patterns emerge: low–low–high (I, upper left), high–low–low (II, upper right), low–high–high (III, lower left), and high–high–low (IV, lower right) in Oe, Wt, and In group respectively. We found that the metabolites involved in amino acid metabolism are enriched in pattern I (P = 0.005, Fisher's exact test), lysolipids are enriched in pattern II (P = 0.0008) and dipeptides are enriched in pattern IV (P = 0.0001).


Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism.

Aughey GN, Grice SJ, Shen QJ, Xu Y, Chang CC, Azzam G, Wang PY, Freeman-Mills L, Pai LM, Sung LY, Yan J, Liu JL - Biol Open (2014)

Global metabolomic profiling indicates negligible changes in CTPsyn activity in vivo.(A) Principle component analysis shows that the samples of wild-type (Wt), CTPsyn inhibition (In), and CTPsyn overexpression (Oe) groups are clearly segregated. Two principal components (PC1 and PC2) are plotted and their proportions of variance are labeled. (B) The mean values of compounds in each state were normalized to (−1,1) and clustered into nine patterns by self-organizing mapping. The numbers of compounds in each pattern are showed on the top of the grids. The patterns that contain the most compounds are indicated by (I, II, III, V). (C) The heat map shows metabolites in major patterns that have significantly differential levels in three groups. Seventy-two metabolites in major patterns of (B) SOM (I, II, III, IV) were selected by one-way ANOVA with Bonferroni adjusted P<10−5. (D) The levels of glutamine in three groups are shown in the boxplot. Glutamine belongs to pattern I and is also colored in red in panel C.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232762&req=5

f05: Global metabolomic profiling indicates negligible changes in CTPsyn activity in vivo.(A) Principle component analysis shows that the samples of wild-type (Wt), CTPsyn inhibition (In), and CTPsyn overexpression (Oe) groups are clearly segregated. Two principal components (PC1 and PC2) are plotted and their proportions of variance are labeled. (B) The mean values of compounds in each state were normalized to (−1,1) and clustered into nine patterns by self-organizing mapping. The numbers of compounds in each pattern are showed on the top of the grids. The patterns that contain the most compounds are indicated by (I, II, III, V). (C) The heat map shows metabolites in major patterns that have significantly differential levels in three groups. Seventy-two metabolites in major patterns of (B) SOM (I, II, III, IV) were selected by one-way ANOVA with Bonferroni adjusted P<10−5. (D) The levels of glutamine in three groups are shown in the boxplot. Glutamine belongs to pattern I and is also colored in red in panel C.
Mentions: Principle component analysis of metabolome data showed that the three groups are clearly distinct from each other in terms of their global metabolite levels (Fig. 5A). We then used a self-organizing map (SOM) to reveal the relative metabolite changes among the three groups for all metabolites. As shown in Fig. 5B, four major patterns emerge: low–low–high (I, upper left), high–low–low (II, upper right), low–high–high (III, lower left), and high–high–low (IV, lower right) in Oe, Wt, and In group respectively. We found that the metabolites involved in amino acid metabolism are enriched in pattern I (P = 0.005, Fisher's exact test), lysolipids are enriched in pattern II (P = 0.0008) and dipeptides are enriched in pattern IV (P = 0.0001).

Bottom Line: Furthermore, our global metabolic profiling demonstrates that CTPsyn overexpression does not significantly alter CTPsyn-related enzymatic activity, suggesting that cytoophidium formation facilitates metabolic stabilisation.In addition, we show that overexpression of CTPsyn only results in moderate increase of CTP pool in human stable cell lines.Together, our study provides experimental evidence, and a mathematical model, for the hypothesis that inactive CTPsyn is incorporated into cytoophidia.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom.

No MeSH data available.


Related in: MedlinePlus