scholarly journals Enzymic imbalance in serine metabolism in rat hepatomas

1986 ◽  
Vol 233 (2) ◽  
pp. 617-620 ◽  
Author(s):  
K Snell ◽  
G Weber
Keyword(s):  
Cancer Cells ◽  
Serine Hydroxymethyltransferase ◽  
Cell Renewal ◽  
Regenerating Liver ◽  
High Cell ◽  
Serine Dehydratase ◽  
Phosphoglycerate Dehydrogenase ◽  
Serine Biosynthesis ◽  
Serine Metabolism

The activity of 3-phosphoglycerate dehydrogenase was high in tissues of high cell-renewal capacity, and was increased in neonatal and regenerating liver and, more markedly, in hepatomas. Serine hydroxymethyltransferase activity was present in hepatomas, whereas other enzymes of serine utilization (serine dehydratase and serine aminotransferase) were absent. This enzymic imbalance couples serine biosynthesis preferentially to nucleotide precursor formation in cancer cells.

scholarly journals The modulation of serine metabolism in hepatoma 3924A during different phases of cellular proliferation in culture

1987 ◽  
Vol 245 (2) ◽  
pp. 609-612 ◽  
Author(s):  
K Snell ◽  
Y Natsumeda ◽  
G Weber
Keyword(s):  
Nucleic Acids ◽  
Cancer Cells ◽  
Growth Phase ◽  
Cellular Proliferation ◽  
Hepatoma Cells ◽  
Serine Hydroxymethyltransferase ◽  
Phosphoglycerate Dehydrogenase ◽  
Serine Metabolism

The activities of 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase increased markedly during the transition of hepatoma cells from a resting non-proliferating culture into the proliferating growth phase. Activities declined as cells reached confluency and entered the plateau growth phase. This pattern was paralleled by changes in [14C]serine incorporation into nucleic acids. The experiments support the hypothesis that the biosynthesis of serine is metabolically coupled to its utilization for nucleotide precursor formation in cancer cells.

scholarly journals The biosynthesis of serine and glycine in Pseudomonas AM1 with special reference to growth on carbon sources other than C1 compounds

1971 ◽  
Vol 121 (5) ◽  
pp. 753-762 ◽  
Author(s):  
W. Harder ◽  
J. R. Quayle
Keyword(s):  
Essential Role ◽  
Carbon Sources ◽  
Enzymic Activity ◽  
Serine Hydroxymethyltransferase ◽  
The Other ◽  
Wild Type ◽  
Phosphoserine Phosphatase ◽  
Wild Type Phenotype ◽  
Phosphoglycerate Dehydrogenase ◽  
Serine Biosynthesis

1. A mutant, 20S, of Pseudomonas AM1 was obtained that requires a supplement of serine to grow on succinate, lactate or ethanol. This mutant lacks phosphoserine phosphatase and revertants to wild-type phenotype regained this enzymic activity showing that the phosphorylated pathway of serine biosynthesis is necessary for growth on these three substrates. 2. The requirement for supplemental serine by mutant 20S could be met by glycine, suggesting that Pseudomonas AM1 can obtain C1 units from glycine. 3. Mutant 20S grows on C1 compounds at a lower rate compared with the wild type. Supplementation with serine stimulated the growth rate of the mutant suggesting that the phosphorylated pathway of serine biosynthesis plays some role, but not an essential role, during growth on C1 compounds. 4. A mutant, 82G, was obtained that requires a supplement of glycine to grow on succinate, lactate or ethanol. When grown in such supplemented media, the mutant lacks serine hydroxymethyltransferase and revertants to wild-type phenotype regained enzymic activity showing that during growth on succinate, lactate or ethanol, glycine is made from serine via serine hydroxymethyltransferase, and that the organism can obtain C1 units from glycine. 5. Mutant 82G grew on methanol and then contained serine hydroxymethyltransferase suggesting that this enzyme is necessary for growth on C1 compounds and that Pseudomonas AM1 may synthesize two such enzymes, one used in growth on C1 compounds, the other used in growth on other substrates. Mutant 82G might lack the latter enzyme. 6. Phosphoglycerate dehydrogenase is specifically inhibited by l-serine and the regulatory implications of this are discussed.

scholarly journals Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers

2016 ◽  
Vol 113 (7) ◽  
pp. 1778-1783 ◽  
Author(s):  
Edouard Mullarky ◽  
Natasha C. Lucki ◽  
Reza Beheshti Zavareh ◽  
Justin L. Anglin ◽  
Ana P. Gomes ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Small Molecule ◽  
Cancer Cell Lines ◽  
Small Molecule Inhibitor ◽  
Genetic Ablation ◽  
Molecule Inhibitor ◽  
Phosphoglycerate Dehydrogenase ◽  
Serine Biosynthesis

Cancer cells reprogram their metabolism to promote growth and proliferation. The genetic evidence pointing to the importance of the amino acid serine in tumorigenesis is striking. The gene encoding the enzyme 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the first committed step of serine biosynthesis, is overexpressed in tumors and cancer cell lines via focal amplification and nuclear factor erythroid-2-related factor 2 (NRF2)-mediated up-regulation. PHGDH-overexpressing cells are exquisitely sensitive to genetic ablation of the pathway. Here, we report the discovery of a selective small molecule inhibitor of PHGDH, CBR-5884, identified by screening a library of 800,000 drug-like compounds. CBR-5884 inhibited de novo serine synthesis in cancer cells and was selectively toxic to cancer cell lines with high serine biosynthetic activity. Biochemical characterization of the inhibitor revealed that it was a noncompetitive inhibitor that showed a time-dependent onset of inhibition and disrupted the oligomerization state of PHGDH. The identification of a small molecule inhibitor of PHGDH not only enables thorough preclinical evaluation of PHGDH as a target in cancers, but also provides a tool with which to study serine metabolism.

scholarly journals MicroRNAs Differentially Regulated by Akt Isoforms Control EMT and Stem Cell Renewal in Cancer Cells

2009 ◽  
Vol 2 (92) ◽  
pp. ra62-ra62 ◽  
Author(s):  
D. Iliopoulos ◽  
C. Polytarchou ◽  
M. Hatziapostolou ◽  
F. Kottakis ◽  
I. G. Maroulakou ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Cells ◽  
Cell Renewal ◽  
Akt Isoforms ◽  
Stem Cell Renewal

L-Serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate dehydrogenase, an enzyme forL-serine biosynthesis

2001 ◽  
Vol 64 (4) ◽  
pp. 392-401 ◽  
Author(s):  
Hiroki Sugishita ◽  
Yasuhide Kuwabara ◽  
Kazuko Toku ◽  
Lisa Doi ◽  
Lihua Yang ◽  
...  
Keyword(s):  
Microglial Cells ◽  
Low Level ◽  
Phosphoglycerate Dehydrogenase ◽  
Serine Biosynthesis

scholarly journals Serine metabolism in the brain regulates starvation-induced sleep suppression in Drosophila melanogaster

2018 ◽  
Vol 115 (27) ◽  
pp. 7129-7134 ◽  
Author(s):  
Jun Young Sonn ◽  
Jongbin Lee ◽  
Min Kyung Sung ◽  
Hwajung Ri ◽  
Jung Kyoon Choi ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Hypomorphic Mutation ◽  
Cholinergic Signaling ◽  
Sleep Behaviors ◽  
Metabolizing Enzyme ◽  
Rate Limiting ◽  
The Brain ◽  
Serine Biosynthesis ◽  
Serine Metabolism ◽  
Genetic Mutants

Sleep and metabolism are physiologically and behaviorally intertwined; however, the molecular basis for their interaction remains poorly understood. Here, we identified a serine metabolic pathway as a key mediator for starvation-induced sleep suppression. Transcriptome analyses revealed that enzymes involved in serine biosynthesis were induced upon starvation in Drosophila melanogaster brains. Genetic mutants of astray (aay), a fly homolog of the rate-limiting phosphoserine phosphatase in serine biosynthesis, displayed reduced starvation-induced sleep suppression. In contrast, a hypomorphic mutation in a serine/threonine-metabolizing enzyme, serine/threonine dehydratase (stdh), exaggerated starvation-induced sleep suppression. Analyses of double mutants indicated that aay and stdh act on the same genetic pathway to titrate serine levels in the head as well as to adjust starvation-induced sleep behaviors. RNA interference-mediated depletion of aay expression in neurons, using cholinergic Gal4 drivers, phenocopied aay mutants, while a nicotinic acetylcholine receptor antagonist selectively rescued the exaggerated starvation-induced sleep suppression in stdh mutants. Taken together, these data demonstrate that neural serine metabolism controls sleep during starvation, possibly via cholinergic signaling. We propose that animals have evolved a sleep-regulatory mechanism that reprograms amino acid metabolism for adaptive sleep behaviors in response to metabolic needs.

scholarly journals The role of high cell density in the promotion of neuroendocrine transdifferentiation of prostate cancer cells

2014 ◽  
Vol 13 (1) ◽  
pp. 113 ◽  
Author(s):  
Zuzana Pernicová ◽  
Eva Slabáková ◽  
Radek Fedr ◽  
Šárka Šimečková ◽  
Josef Jaroš ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cell Density ◽  
High Cell Density ◽  
High Cell ◽  
Prostate Cancer Cells ◽  
Neuroendocrine Transdifferentiation
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