Urea Synthesis and Metabolism of Arginine and Citrulline

Ratner, S.

doi:10.1002/9780470122600.ch8

Cited by 15 publications

(2 citation statements)

References 155 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Citrulline could be metabolized by arginine deiminase (EC3.5.3.6) or oxidoreductases (EC1.14.13.39/EC1.14.13.165). Arginine deiminase acts on carbon-nitrogen bonds [ 43 ]. Oxidoreductases act on paired donors, with incorporation or reduction of molecular oxygen on arginine biosynthesis [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

RNA-seq transcriptional profiling of Leishmania amazonensis reveals an arginase-dependent gene expression regulation

et al. 2017

View full text Add to dashboard Cite

BackgroundLeishmania is a protozoan parasite that alternates its life cycle between the sand-fly vector and the mammalian host. This alternation involves environmental changes and leads the parasite to dynamic modifications in morphology, metabolism, cellular signaling and regulation of gene expression to allow for a rapid adaptation to new conditions. The L-arginine pathway in L. amazonensis is important during the parasite life cycle and interferes in the establishment and maintenance of the infection in mammalian macrophages. Host arginase is an immune-regulatory enzyme that can reduce the production of nitric oxide by activated macrophages, directing the availability of L-arginine to the polyamine pathway, resulting in parasite replication. In this work, we performed transcriptional profiling to identify differentially expressed genes in L. amazonensis wild-type (La-WT) versus L. amazonensis arginase knockout (La-arg-) promastigotes and axenic amastigotes.Methodology/Principal findingsA total of 8253 transcripts were identified in La-WT and La-arg- promastigotes and axenic amastigotes, about 60% of them codifying hypothetical proteins and 443 novel transcripts, which did not match any previously annotated genes. Our RNA-seq data revealed that 85% of genes were constitutively expressed. The comparison of transcriptome and metabolome data showed lower levels of arginase and higher levels of glutamate-5-kinase in La-WT axenic amastigotes compared to promastigotes. The absence of arginase activity in promastigotes increased the levels of pyrroline 5-carboxylate reductase, but decreased the levels of arginosuccinate synthase, pyrroline 5-carboxylate dehydrogenase, acetylornithine deacetylase and spermidine synthase transcripts levels. These observations can explain previous metabolomic data pointing to the increase of L-arginine, citrulline and L-glutamate and reduction of aspartate, proline, ornithine and putrescine. Altogether, these results indicate that arginase activity is important in Leishmania gene expression modulation during differentiation and adaptation to environmental changes. Here, we confirmed this hypothesis with the identification of differential gene expression of the enzymes involved in biosynthesis of amino acids, arginine and proline metabolism and arginine biosynthesis.Conclusions/SignificanceAll data provided information about the transcriptomic profiling and the expression levels of La-WT and La-arg- promastigotes and axenic amastigotes. These findings revealed the importance of arginase in parasite survival and differentiation, and indicated the existence of a coordinated response in the absence of arginase activity related to arginine and polyamine pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

RNA-seq transcriptional profiling of Leishmania amazonensis reveals an arginase-dependent gene expression regulation

et al. 2017

View full text Add to dashboard Cite

show abstract

“…ASS1 converts citrulline and aspartate into L-argininosuccinate, an intermediate in arginine biosynthesis, which is also important for alanine, aspartate and glutamine metabolism. ACSS1 encodes a protein that catalyses the conversion of acetate to acetyl-CoA [24][25][26]. ASS1 was only expressed in ARR cells, whereas ACSS1 had the opposite pattern, with higher expression levels found in the SIL-TAL cells ( Figure 1C,D).…”

Section: Sil-tal Cells Exhibit Suppressed Carbohydrate and Upregulatementioning

confidence: 99%

T-ALL Proliferation Relies on Glutamine Uptake and EAAT1-dependent Conversion of Glutamine to Aspartate and Nucleotides

Stanulović

Reed

Patani

et al. 2020

Preprint

View full text Add to dashboard Cite

T-cell acute lymphoblastic leukaemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients relapse and die from the disease. To improve patient outcome new drugs are needed. With the aim to identify new therapeutic targets, we integrated transcriptomics and metabolomics data, including live-cell NMR-spectroscopy, of cell lines and patient samples. We found that T-ALL cells have limited energy availability, resulting in active AMPK-signalling and reduced autophagy. Despite this, mTOR kinase remains active and essential for glutamine-uptake that fuels rapid proliferation.Glutamine fuels aspartate synthesis and together they supply three nitrogen atoms in purines and all atoms but one carbon in pyrimidine rings. We show that EAAT1, a glutamateaspartate transporter normally only expressed in the CNS, is crucial for glutamine conversion to nucleotides and that T-ALL cell proliferation depends on EAAT1 function, identifying it as a target for T-ALL treatment. Finally, we performed an in silico screen and identified a novel EAAT1-specific allosteric inhibitor.

show abstract

Les Voies Principales De L'assimilation Et Dissimilation De L'Azote Chez Les Animaux

Braunstein¹

1957

Advances in Enzymology - And Related Areas of Molecular Biology

View full text Add to dashboard Cite

Urea Synthesis and Metabolism of Arginine and Citrulline

Cited by 15 publications

References 155 publications

RNA-seq transcriptional profiling of Leishmania amazonensis reveals an arginase-dependent gene expression regulation

RNA-seq transcriptional profiling of Leishmania amazonensis reveals an arginase-dependent gene expression regulation

T-ALL Proliferation Relies on Glutamine Uptake and EAAT1-dependent Conversion of Glutamine to Aspartate and Nucleotides

Les Voies Principales De L'assimilation Et Dissimilation De L'Azote Chez Les Animaux

Contact Info

Product

Resources

About