scholarly journals Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2584 ◽  
Author(s):  
Lucia A. Seale ◽  
Vedbar S. Khadka ◽  
Mark Menor ◽  
Guoxiang Xie ◽  
Ligia M. Watanabe ◽  
...  
Keyword(s):  
Amino Acid ◽  
Metabolic Pathways ◽  
Redox Reactions ◽  
Acid Metabolism ◽  
Lipid Homeostasis ◽  
Selenium Metabolism ◽  
Glycine Metabolism ◽  
Integrated Omics ◽  
Selenocysteine Lyase ◽  
Glucose And Lipid Homeostasis

Selenium is a nonmetal trace element that is critical for several redox reactions and utilized to produce the amino acid selenocysteine (Sec), which can be incorporated into selenoproteins. Selenocysteine lyase (SCL) is an enzyme which decomposes Sec into selenide and alanine, releasing the selenide to be further utilized to synthesize new selenoproteins. Disruption of the selenocysteine lyase gene (Scly) in mice (Scly−/− or Scly KO) led to obesity with dyslipidemia, hyperinsulinemia, glucose intolerance and lipid accumulation in the hepatocytes. As the liver is a central regulator of glucose and lipid homeostasis, as well as selenium metabolism, we aimed to pinpoint hepatic molecular pathways affected by the Scly gene disruption. Using RNA sequencing and metabolomics, we identified differentially expressed genes and metabolites in the livers of Scly KO mice. Integrated omics revealed that biological pathways related to amino acid metabolism, particularly alanine and glycine metabolism, were affected in the liver by disruption of Scly in mice with selenium adequacy. We further confirmed that hepatic glycine levels are elevated in male, but not in female, Scly KO mice. In conclusion, our results reveal that Scly participates in the modulation of hepatic amino acid metabolic pathways.

scholarly journals Comprehensive transcriptome and metabolome profiling reveal metabolic mechanisms of Nitraria sibirica Pall. to salt stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huanyong Li ◽  
Xiaoqian Tang ◽  
Xiuyan Yang ◽  
Huaxin Zhang
Keyword(s):  
Salt Stress ◽  
Amino Acid ◽  
Salt Tolerance ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Sulfur Metabolism ◽  
Enrichment Analysis ◽  
Extracellular Region ◽  
Nitraria Sibirica

AbstractNitraria sibirica Pall., a typical halophyte that can survive under extreme drought conditions and in saline-alkali environments, exhibits strong salt tolerance and environmental adaptability. Understanding the mechanism of molecular and physiological metabolic response to salt stress of plant will better promote the cultivation and use of halophytes. To explore the mechanism of molecular and physiological metabolic of N. sibirica response to salt stress, two-month-old seedlings were treated with 0, 100, and 400 mM NaCl. The results showed that the differentially expressed genes between 100 and 400 mmol L−1 NaCl and unsalted treatment showed significant enrichment in GO terms such as binding, cell wall, extemal encapsulating structure, extracellular region and nucleotide binding. KEGG enrichment analysis found that NaCl treatment had a significant effect on the metabolic pathways in N. sibirica leaves, which mainly including plant-pathogen interaction, amino acid metabolism of the beta alanine, arginine, proline and glycine metabolism, carbon metabolism of glycolysis, gluconeogenesis, galactose, starch and sucrose metabolism, plant hormone signal transduction and spliceosome. Metabolomics analysis found that the differential metabolites between the unsalted treatment and the NaCl treatment are mainly amino acids (proline, aspartic acid, methionine, etc.), organic acids (oxaloacetic acid, fumaric acid, nicotinic acid, etc.) and polyhydric alcohols (inositol, ribitol, etc.), etc. KEGG annotation and enrichment analysis showed that 100 mmol L−1 NaCl treatment had a greater effect on the sulfur metabolism, cysteine and methionine metabolism in N. sibirica leaves, while various amino acid metabolism, TCA cycle, photosynthetic carbon fixation and sulfur metabolism and other metabolic pathways have been significantly affected by 400 mmol L−1 NaCl treatment. Correlation analysis of differential genes in transcriptome and differential metabolites in metabolome have found that the genes of AMY2, BAM1, GPAT3, ASP1, CML38 and RPL4 and the metabolites of L-cysteine, proline, 4-aminobutyric acid and oxaloacetate played an important role in N. sibirica salt tolerance control. This is a further improvement of the salt tolerance mechanism of N. sibirica, and it will provide a theoretical basis and technical support for treatment of saline-alkali soil and the cultivation of halophytes.

scholarly journals The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 675 ◽  
Author(s):  
Bo-Hyun Choi ◽  
Jonathan L. Coloff
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cancer Therapy ◽  
Metabolic Pathways ◽  
Essential Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
Redox Status ◽  
Antioxidant Systems

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.

Xuebijing Injection Affects the Dynamic Change of Metabolism in CLP-Induced Septic Rats

2021 ◽  
Author(s):  
Yanjuan Liu ◽  
Qi Zeng ◽  
Wen Xiao ◽  
Fang Chen ◽  
Lianhong Zou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Dynamic Change ◽  
Sepsis Group ◽  
Control Group ◽  
Multivariate Statistical ◽  
Xuebijing Injection ◽  
Kegg Pathway Analysis

Abstract Xuebijing injection has been widely applied to treat sepsis. However, its roles in the dynamic change of metabolism in sepsis are still unknown. In our study, Gas chromatography-mass spectrometer (GC-MS) combined with multivariate statistical techniques was used to detect the metabolic change in septic rats with or without XBJ injection treatment. The KEGG pathway analysis was used to further analyze the related metabolic pathways in which the identified metabolites were involved. Based on the fold change, variable important in projection, and P value, we found 11, 33 and 26 differential metabolites in the sepsis group at 2, 6 and 12 hours post CLP, compared with the control group. Besides, we also found 32, 23 and 28 differential metabolites in the XBJ group at 2, 6 and 12 hours post CLP. The related pathways of differential metabolites were glycometabolism at 2h, glycometabolism and amino acid metabolism at 6h and amino acid metabolism at 12h post CLP in the sepsis group compared with the control group. Besides, glycometabolism, amino acid metabolism and lipid metabolism changed markedly after XBJ injection for 2 hours; while only amino acid metabolism changed significantly with the treatment of XBJ injection for 6 and 12 hours, compared with the sepsis group. Further analysis showed 3, 6 and 6 differential metabolites were overlapped in the sepsis group and XBJ group at 2, 6 and 12 hours post CLP. These identified differential metabolites were majorly involved in arginine and proline metabolism, suggesting that XBJ injection is capable of improving metabolic disorders in CLP-induced septic rat to a certain extent.

scholarly journals Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Tomé
Keyword(s):  
Amino Acid ◽  
Metabolic Pathways ◽  
Microbial Growth ◽  
Acid Metabolism ◽  
Protein Translation ◽  
Host Protein ◽  
T Cell Proliferation ◽  
Immune Functions ◽  
Infected Cells ◽  
Antimicrobial Metabolites

AbstractDefences to pathogens such as SarCoV2 in mammals involves interactions between immune functions and metabolic pathways to eradicate infection while preventing hyperinflammation. Amino acid metabolic pathways represent with other antimicrobial agent potential targets for therapeutic strategies. iNOS-mediated production of NO from Arg is involved in the innate inflammatory response to pathogens and NO overproduction can induce hyperinflammation. The two Arg-catabolising enzymes Arg1 and IDO1 reduce the hyperinflammation by an immunosuppressive effect via either Arg starvation (for Arg1) or via the immunoregulatory activity of the Arg-derived metabolites Kyn (for IDO1). In response to amino acid abundance mTOR activates the host protein translation and Coronaviruses use this machinery for their own protein synthesis and replication. In contrast GCN2, the sensor of amino acid starvation, activates pathways that restrict inflammation and viral replication. Gln depletion alters the immune response that become more suppressive, by favouring a regulatory T phenotype rather than a Th1 phenotype. Proliferating activated immune cells are highly dependent on Ser, activation and differentiation of T cells need enough Ser and dietary Ser restriction can inhibit their proliferation. Cys is strictly required for T-cell proliferation because they cannot convert Met to Cys. Restricting Met inhibits both viral RNA cap methylation and replication, and the proliferation of infected cells with an increased requirement for Met. Phe catabolism produces antimicrobial metabolites resulting in the inhibition of microbial growth and an immunosuppressive activity towards T lymphocytes.

scholarly journals Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity

2021 ◽  
Author(s):  
Daniel Tomé
Keyword(s):  
Amino Acid ◽  
Metabolic Pathways ◽  
Microbial Growth ◽  
Acid Metabolism ◽  
Protein Translation ◽  
Host Protein ◽  
T Cell Proliferation ◽  
Immune Functions ◽  
Infected Cells ◽  
Antimicrobial Metabolites

AbstractDefences to pathogens such as SarCoV2 in mammals involves interactions between immune functions and metabolic pathways to eradicate infection while preventing hyperinflammation. Amino acid metabolic pathways represent with other antimicrobial agent potential targets for therapeutic strategies. iNOS-mediated production of NO from Arg is involved in the innate inflammatory response to pathogens and NO overproduction can induce hyperinflammation. The two Arg-catabolising enzymes Arg1 and IDO1 reduce the hyperinflammation by an immunosuppressive effect via either Arg starvation (for Arg1) or via the immunoregulatory activity of the Arg-derived metabolites Kyn (for IDO1). In response to amino acid abundance mTOR activates the host protein translation and Coronaviruses use this machinery for their own protein synthesis and replication. In contrast GCN2, the sensor of amino acid starvation, activates pathways that restrict inflammation and viral replication. Gln depletion alters the immune response that become more suppressive, by favouring a regulatory T phenotype rather than a Th1 phenotype. Proliferating activated immune cells are highly dependent on Ser, activation and differentiation of T cells need enough Ser and dietary Ser restriction can inhibit their proliferation. Cys is strictly required for T-cell proliferation because they cannot convert Met to Cys. Restricting Met inhibits both viral RNA cap methylation and replication, and the proliferation of infected cells with an increased requirement for Met. Phe catabolism produces antimicrobial metabolites resulting in the inhibition of microbial growth and an immunosuppressive activity towards T lymphocytes.

scholarly journals Integrated Metabolomic and Transcriptomic Profiling Reveals Novel Activation-Induced Metabolic Networks in Human T cells

2019 ◽  
Author(s):  
S. Hiemer ◽  
S. Jatav ◽  
J. Jussif ◽  
J. Alley ◽  
S. Lathwal ◽  
...  
Keyword(s):  
T Cells ◽  
Amino Acid ◽  
T Cell ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Cell Function ◽  
Immune Cell ◽  
Transcriptomic Profiling ◽  
Human T Cell

AbstractThe targeting of metabolic pathways is emerging as an exciting new approach for modulating immune cell function and polarization states. In this study, carbon tracing and systems biology approaches integrating metabolomic and transcriptomic profiling data were used to identify adaptations in human T cell metabolism important for fueling pro-inflammatory T cell function. Results of this study demonstrate that T cell receptor (TCR) stimulation leads to a significant increase in glucose and amino acid metabolism that trigger downstream biosynthetic processes. Specifically, increased expression of several enzymes such as CTPS1, IL4I1, and ASL results in the reprogramming of amino acid metabolism. Additionally, the strength of TCR signaling resulted in different metabolic enzymes utilized by T cells to facilitate similar biochemical endpoints. Furthermore, this study shows that cyclosporine represses the pathways involved in amino acid and glucose metabolism, providing novel insights on the immunosuppressive mechanisms of this drug. To explore the implications of the findings of this study in clinical settings, conventional immunosuppressants were tested in combination with drugs that target metabolic pathways. Results showed that such combinations increased efficacy of conventional immunosuppressants. Overall, the results of this study provide a comprehensive resource for identifying metabolic targets for novel combinatorial regimens in the treatment of intractable immune diseases.

scholarly journals POS0421 COMBINED ANALYSIS OF METABOLIC AND TRANSCRIPTOMIC KIDNEY PROFILES OF NZW/B-F1 MURINE LUPUS UNCOVERS BIOLOGICAL MECHANISMS PRECEDING THE ONSET OF NEPHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 439.2-440
Author(s):  
T. Manolakou ◽  
I. Tsiara ◽  
D. Nikolopoulos ◽  
P. Garantziotis ◽  
D. Benaki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Differentially Expressed Genes ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Univariate Analysis ◽  
Differentially Expressed ◽  
Disease Stage ◽  
Cellular Respiration ◽  
H Nmr

Background:Metabolic pathways are important regulators of immune differentiation and activation in kidneys. Kidneys directly impact systemic metabolism, circulating metabolite levels, and express intrinsic metabolic activity. The integration of renal metabolomic and transcriptomic profiles may unravel unique gene-metabolite pairs of biological significance in lupus nephritis (LN).Objectives:To decipher gene-metabolite signatures at both pre-nephritic and nephritic stages of lupus.Methods:Kidneys were isolated and snap-frozen after perfusion from female NZB/NZW-F1 lupus mice at the pre-nephritic (3-month-old) and nephritic (6-month-old exhibiting ≥100 ng/dL of urine protein) stage of lupus (n=6/group). Age-matched female C57BL/6 mice were used as healthy controls. Sample extracts were used for RNA sequencing and 1H-NMR spectroscopy metabolic profiling. DESeq2 was used to identify differentially expressed genes. Univariate analysis was used to reveal metabolic differences characteristic for nephritis.Results:Comparative transcriptomic analyses uncovered multiple transcripts related to metabolic pathways: In pre-nephritic kidneys, lipid metabolism, cellular respiration, TCA cycle, amino acid metabolism processes were overrepresented in the upregulated genes while in nephritic kidneys, amino acid metabolism processes were overrepresented among the downregulated genes (Figure 1). 1H-NMR analysis revealed a total of 49 metabolites. Comparison of the metabolic levels of nephritic and pre-nephritic animals revealed that ADP, ATP, NAD+, Taurine and Myo-inositol decreased, while Thr increased significantly. The comparison to corresponding control animals, demonstrated that only myo-inositol increased significantly. Integration of kidney metabolomics and transcriptomics indicated the involvement of processes related to glutathione metabolism, leukocyte trans-endothelial migration and antigen presentation during the established renal disease stage.Conclusion:The combined transcriptomics and metabolomics analysis revealed metabolic derangements in lupus-affected kidneys both during subclinical and overt LN. Deregulated tissue-levels of taurine and myo-inositol at the subclinical stage of the disease suggest aberrant renal biochemistry preceding the development of overt LN that may directly impact systemic metabolism and circulating metabolite levels.Figure 1.Pathways linked to cell metabolism were overrepresented among 3-month upregulated and 6-month lupus mice (F1) downregulated DEGS (differentially expressed genes) compared to controls (C57BL/6).Acknowledgements:This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 742390).Disclosure of Interests:None declared

HYPERGLYCINEMIA WITH KETOACIDOSIS AND LEUKOPENIA

PEDIATRICS ◽  
1967 ◽  
Vol 39 (6) ◽  
pp. 818-828 ◽  
Author(s):  
Juan Rodriguez Soriano ◽  
Leonard S. Taitz ◽  
Laurence Finberg ◽  
Chester M. Edelmann
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Intake ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Amino Acid Mixture ◽  
Acid Mixture ◽  
Glycine Metabolism ◽  
Biochemical Features

Metabolic investigations are reported in a patient with the clinical and biochemical features of "idiopathic hyperglycinemia." During ketoacidosis elevated concentrations in serum of numerous amino acids were noted, especially leucine, isoleucine, valine, glycine, and lysine. Hyperammonemia was found in association with ketoacidosis. Clinical and biochemical amelioration was induced by restriction of protein intake to 1 gm/kg or less. Although exacerbation was produced by increasing the protein intake to 1.5 gm/kg, the patient was able to tolerate as much as 3.0 gm/kg of an amino acid mixture in which leucine, isoleucine, valine, methionine, and threonine were absent. It is postulated that this disease, in contrast to hyperglycinemia caused by a specific disorder in glycine metabolism, represents a generalized defect in utilization of amino acids resulting in excessive deamination of certain amino acids in the muscle, with consequent hyperammonemia and ketoacidosis. The nature of the defect in amino acid metabolism is unknown.

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