scholarly journals Phosphoserine Aminotransferase Deficiency: A Novel Disorder of the Serine Biosynthesis Pathway

2007 ◽  
Vol 80 (5) ◽  
pp. 931-937 ◽  
Author(s):  
Claire E. Hart ◽  
Valerie Race ◽  
Younes Achouri ◽  
Elsa Wiame ◽  
Mark Sharrard ◽  
...  
Keyword(s):  
Biosynthesis Pathway ◽  
Phosphoserine Aminotransferase ◽  
Serine Biosynthesis

scholarly journals Artemether Exhibits Amoebicidal Activity against Acanthamoeba castellanii through Inhibition of the Serine Biosynthesis Pathway

2015 ◽  
Vol 59 (8) ◽  
pp. 4680-4688 ◽  
Author(s):  
Yihong Deng ◽  
Wei Ran ◽  
Suqin Man ◽  
Xueping Li ◽  
Hongjian Gao ◽  
...  
Keyword(s):  
Acanthamoeba Castellanii ◽  
Dependent Manner ◽  
Biosynthesis Pathway ◽  
Content Type ◽  
Phosphoserine Aminotransferase ◽  
Proteomic Approach ◽  
Phosphoglycerate Dehydrogenase ◽  
Serine Biosynthesis ◽  
Amoebicidal Activity

ABSTRACTAcanthamoebasp. parasites are the causative agents ofAcanthamoebakeratitis, fatal granulomatous amoebic encephalitis, and cutaneous infections. However, there are currently no effective drugs for these organisms. Here, we evaluated the activity of the antimalarial agent artemether againstAcanthamoeba castellaniitrophozoites and identified potential targets of this agent through a proteomic approach. Artemether exhibitedin vitroamoebicidal activity in a time- and dose-dependent manner and induced ultrastructural modification and cell apoptosis. The iTRAQ quantitative proteomic analysis identified 707 proteins that were differentially expressed after artemether treatment. We focused on phosphoglycerate dehydrogenase and phosphoserine aminotransferase in the serine biosynthesis pathway because of their importance to the growth and proliferation of protozoan and cancer cells. The expression of these proteins inAcanthamoebawas validated using quantitative real-time PCR and Western blotting after artemether treatment. The changes in the expression levels of phosphoserine aminotransferase were consistent with those of phosphoglycerate dehydrogenase. Therefore, the downregulation of phosphoserine aminotransferase may be due to the downregulation of phosphoglycerate dehydrogenase. Furthermore, exogenous serine might antagonize the activity of artemether againstAcanthamoebatrophozoites. These results indicate that the serine biosynthesis pathway is important to amoeba survival and that targeting these enzymes would improve the treatment ofAcanthamoebainfections. Artemether may be used as a phosphoglycerate dehydrogenase inhibitor to control or blockAcanthamoebainfections.

scholarly journals Serine Biosynthesis Pathway Supports MYC–miR-494–EZH2 Feed-Forward Circuit Necessary to Maintain Metabolic and Epigenetic Reprogramming of Burkitt Lymphoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 580 ◽  
Author(s):  
Emilia Białopiotrowicz ◽  
Monika Noyszewska-Kania ◽  
Neli Kachamakova-Trojanowska ◽  
Agnieszka Łoboda ◽  
Magdalena Cybulska ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Species Abundance ◽  
Negative Regulator ◽  
Biosynthesis Pathway ◽  
Genetic Ablation ◽  
Myc Oncogene ◽  
Phosphoserine Aminotransferase ◽  
Induced Apoptosis ◽  
Serine Biosynthesis

Burkitt lymphoma (BL) is a rapidly growing tumor, characterized by high anabolic requirements. The MYC oncogene plays a central role in the pathogenesis of this malignancy, controlling genes involved in apoptosis, proliferation, and cellular metabolism. Serine biosynthesis pathway (SBP) couples glycolysis to folate and methionine cycles, supporting biosynthesis of certain amino acids, nucleotides, glutathione, and a methyl group donor, S-adenosylmethionine (SAM). We report that BLs overexpress SBP enzymes, phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1). Both genes are controlled by the MYC-dependent ATF4 transcription factor. Genetic ablation of PHGDH/PSAT1 or chemical PHGDH inhibition with NCT-503 decreased BL cell lines proliferation and clonogenicity. NCT-503 reduced glutathione level, increased reactive oxygen species abundance, and induced apoptosis. Consistent with the role of SAM as a methyl donor, NCT-503 decreased DNA and histone methylation, and led to the re-expression of ID4, KLF4, CDKN2B and TXNIP tumor suppressors. High H3K27me3 level is known to repress the MYC negative regulator miR-494. NCT-503 decreased H3K27me3 abundance, increased the miR-494 level, and reduced the expression of MYC and MYC-dependent histone methyltransferase, EZH2. Surprisingly, chemical/genetic disruption of SBP did not delay BL and breast cancer xenografts growth, suggesting the existence of mechanisms compensating the PHGDH/PSAT1 absence in vivo.

Phosphoserine Aminotransferase, the Second Step-Catalyzing Enzyme for Serine Biosynthesis

IUBMB Life ◽  
1999 ◽  
Vol 48 (5) ◽  
pp. 525-529 ◽  
Author(s):  
Marie-Jose Basurko ◽  
Michele Marche ◽  
Monique Darriet ◽  
Andre Cassaigne
Keyword(s):  
Second Step ◽  
Phosphoserine Aminotransferase ◽  
Serine Biosynthesis

scholarly journals P.067 Phosphoserine aminotransferase (PSAT) deficiency: Imaging findings in a child with congenital microcephaly

2018 ◽  
Vol 45 (s2) ◽  
pp. S33-S33
Author(s):  
G Shapira Zaltsberg ◽  
H McMillan ◽  
E Miller
Keyword(s):  
Intractable Epilepsy ◽  
Mri Findings ◽  
Phosphoserine Aminotransferase ◽  
Magnetic Resonance Imaging Mri ◽  
Biochemical Testing ◽  
Congenital Microcephaly ◽  
Biallelic Mutations ◽  
Serine Biosynthesis ◽  
Torch Infections

Background: Serine deficiency disorders can result from deficiency in one of three enzymes. Deficiency of the second enzyme in the serine biosynthesis pathway, 3-phosphoserine aminotransferase (PSAT), has been reported in two siblings when the eldest was investigated for acquired microcephaly, progressive spasticity and intractable epilepsy. Methods: Our patient had neurological symptoms apparent at birth. Fetal magnetic resonance imaging (MRI) at 35 weeks gestation demonstrated microencephaly and simplification of the the gyration (anterior>posterior) which was confirmed upon subsequent post-natal MRI. Congenital microcephaly was apparent at birth. Results: PSAT deficiency was confirmed when exome sequencing identified biallelic mutations in PSAT1; c.44C>T, p.Ala15Val and; c.432delA, p.Pro144fs and biochemical testing noted low plasma serine 22 mcmol/L (normal 83-212 mcmol/L) and low CSF serine 10 mcmol/L (normal 22-61 mcmol/L). Despite oral serine and glycine supplementation at 4 months old the patient showed little neurodevelopmental progress and developed epileptic spasms at 10 months old. Serological testing for TORCH infections was negative. Conclusions: PSAT deficiency should be considered for patients with congenital microcephaly. Although further characterization of MRI findings in other patients is required, microencephaly with simplified gyral pattern could provide imaging clues for this rare metabolic disorder.

2-Phosphoglycerate phosphatase and serine biosynthesis in Veillonella alcalescens

1981 ◽  
Vol 27 (8) ◽  
pp. 808-814 ◽  
Author(s):  
J. J. Pestka ◽  
E. A. Delwiche
Keyword(s):  
Biosynthetic Pathway ◽  
Gel Filtration ◽  
Deae Cellulose ◽  
Apparent Molecular Weight ◽  
Ammonium Sulfate Precipitation ◽  
Ph Optimum ◽  
Phosphoserine Aminotransferase ◽  
Cell Extracts ◽  
Phosphoglycerate Dehydrogenase ◽  
Serine Biosynthesis

The constituent enzymes for the phosphorylated and nonphosphorylated serine biosynthetic pathways in Veillonella alcalescens were identified and included phosphoserine phosphatase, 3-phosphoglycerate dehydrogenase, glycerate dehydrogenase, phosphoserine aminotransferase, and serine–pyruvate aminotransferase. Cell extracts of the organism were also found to cause the specific dephosphorylation of 2-phosphoglycerate. The phosphatase was purified 39-fold by manganese chloride precipitation, ammonium sulfate precipitation, and DEAE-cellulose chromatography. Sephadex G-200 gel filtration data established an apparent molecular weight of 50 000 for the enzyme. The 2-phosphoglycerate phosphatase had a pH optimum of 5.5 and was distinct from phosphoglyceromutase. Assays conducted with the purified enzyme on a number of other phosphorylated intermediates indicated that the phosphatase was most specific for 2-phosphoglycerate. Glucerate, hydroxypyruvate, and serine inhibited the enzyme, whereas succinate stimulated activity. Veillonella 2-phosphoglycerate phosphatase is the first such enzyme to be described in a prokaryote and is probably involved in glycerate generation for the nonphosphorylated serine biosynthetic pathway.

scholarly journals Phosphoserine Aminotransferase, the Second Step-Catalyzing Enzyme for Serine Biosynthesis

IUBMB Life ◽  
1999 ◽  
Vol 48 (5) ◽  
pp. 525-529 ◽  
Author(s):  
Marie-Jose Basurko ◽  
Michele Marche ◽  
Monique Darriet ◽  
Andre Cassaigne
Keyword(s):  
Second Step ◽  
Phosphoserine Aminotransferase ◽  
Serine Biosynthesis

scholarly journals Targeting Asparagine and Serine Metabolism in Germinal Centre-Derived B Cells Non-Hodgkin Lymphomas (B-NHL)

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2589
Author(s):  
Zuhal Eraslan ◽  
Grigorios Papatzikas ◽  
Jean-Baptiste Cazier ◽  
Farhat L. Khanim ◽  
Ulrich L. Günther
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Germinal Centre ◽  
Biosynthesis Pathway ◽  
Genetic Characteristics ◽  
Diagnostic Potential ◽  
Combined Use ◽  
Serine Biosynthesis ◽  
Serine Metabolism

BL and DLBCL are subtypes of B-cell lymphomas that arise from germinal centre B lymphocytes. Differentiation between BL and DLBCL is critical and can be challenging, as these two types of cancer share the same morphological, immunophenotypic, and genetic characteristics. In this study, we have examined metabolism in BL and DLBCL lymphomas and found distinctive differences in serine metabolism. We show that BL cells consume significantly more extracellular asparagine than DLBCL cells. Using a tracer-based approach, we find that asparagine regulates the serine uptake and serine synthesis in BL and DLBCL cells. Calculation of Differentially Expressed Genes (DEGs) from RNAseq datasets of BL and DLBCL patients show that BL cancers express the genes involved in serine synthesis at a higher level than DLBCL. Remarkably, combined use of an inhibitor of serine biosynthesis pathway and an anticancer drug asparaginase increases the sensitivity of BL cells to extracellular asparagine deprivation without inducing a change in the sensitivity of DLBCL cells to asparaginase. In summary, our study unravels metabolic differences between BL and DLBCL with diagnostic potential which may also open new avenues for treatment.

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