Nature Communications
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2025
·Vol. 16
·期 1
·1-16
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IF 15.7
Gao Yang,Luo Mingdu,Wang Hongmiao,Zhou Zhiwei,Yin Yandong,Wang Ruohong,Xing Beizi,Yang Xiaohua,Cai Yuping,Zhu Zheng-Jiang
Metabolic reactions play important roles in organisms such as providing energy, transmitting signals, and synthesizing biomacromolecules. Charting unknown metabolic reactions in cells is hindered by limited technologies, restricting the holistic understanding of cellular metabolism. Using mass spectrometry-resolved stable-isotope tracing metabolomics, we develop an isotopologue similarity networking strategy, namely IsoNet, to effectively deduce previously unknown metabolic reactions. The strategy uncovers ~300 previously unknown metabolic reactions in living cells and mice. Specifically, we elaborately chart the metabolic reaction network related to glutathione, unveiling three previously unreported reactions nestled within glutathione metabolism. Among these, a transsulfuration reaction, synthesizing γ-glutamyl-seryl-glycine directly from glutathione, underscores the role of glutathione as a sulfur donor. Functional metabolomics studies systematically characterize biochemical effects of previously unknown reactions in glutathione metabolism, showcasing their diverse functions in regulating cellular metabolism. Overall, these newly uncovered metabolic reactions fill gaps in the metabolic network maps, facilitating exploration of uncharted territories in cellular biochemistry.
研究领域:
生物化学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL MANAGEMENT
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2024
·
IF 8
Xun Weng,Meng-Jiao Gao,Zheng Mao,Hui-Min Fu,Shi-Jun Li,Peng Yan,You-Peng Chen
Iron nanoparticles (FeNPs) generated from industrial activities could end up into the sewer system, and potentially affect wastewater treatment processes. The impact of FeNPs on anammox process is getting increasing attention. However, the resistance mechanism of anammox granular sludge (AnGS) to FeNPs has not been fully elucidated. The current study investigated the metabolic and morphological response of AnGS to acute and chronic FeNPs exposure. Results showed that nitrogen removal efficiencies were elevated at 1–4 mM FeNPs concentrations compared to 0–0.5 mM FeNPs. Extracellular protein and tyrosine-like and tryptophan-like fluorophore secretions of AnGS were stimulated by FeNPs, which largely contributed to the adsorption of FeNPs on AnGS surface. FeNPs exposure triggered higher necrotic fraction of AnGS compared with no FeNPs condition. Highly absorbed particles appeared inside the bacterial cells of AnGS, soft X-ray imaging illustrated that anammox bacteria maintained intact cellular and anammoxosome structures whereas non-anammox bacterial structures were damaged under FeNPs exposure. Anammox bacterial abundance increased from 4.84% to 20.64%, when FeNPs concentrations increased from 0 mM to 4 mM, and anammoxosome membrane ensured anammox bacterial metabolism under FeNPs exposure. This study extended fundamental understanding of AnGS resistance mechanisms to FeNPs.
研究领域:
环境科学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Baoyan Ding,Wei Meng,Xiaoling Zang,Zhihua Lv
A small molecule, (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate (SEC), has been reported to be capable of suppressing metastasis of prostate cancer (PCa) cells. In this study, SEC was used to study the metabolic responses of PCa cell lines (LNCaP, PC3, and DU145) with different metastatic potential and the alterations of mTOR, p-mTOR, AMPK, and p-AMPK levels, when the PCa cells were inhibited. The ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based analysis showed that SEC induced the decreases of intracellular metabolites including glutamic acid, glutamine, and histidine (LNCaP); creatinine, citric acid/isocitric acid, and aspartic acid (PC3); and spermidine, S-hydroxymethylglutathione, LPE (20:3), and palmitic amide (DU145), and the increases of intracellular LPC (18:0) (LNCaP); tyrosine, pyroglutamic acid/pyrroline hydroxycarboxylic acid (PC3); and tyrosine, phenylalanine, phenylacetylglycine, spermine, histidine, and choline (DU145). SEC also caused the decrease of extracellular N1-acetylspermidine (LNCaP), erythronic acid/threonic acid (PC3 and DU145), and nicotinic acid/picolinic acid (DU145), and the increase of extracellular 5’-methylthioadenosine (DU145). High metastatic PC3 and DU145 cells exhibited changes in aromatic amino acid metabolism including tyrosine metabolism, phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism (PC3 and DU145), TCA cycle (PC3), arginine and proline metabolism, and glycerophospholipid metabolism (DU145), different from the low metastatic LNCaP cells, which had changes in alanine, aspartate, and glutamate metabolism, and arginine biosynthesis. In addition, the levels of p-mTOR and p-AMPK were shown to be obviously downregulated and upregulated, respectively, in high metastatic PC3 and DU145 cells upon SEC inhibition, while this behavior was not detected in LNCaP cells.
研究领域:
肿瘤学
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代谢组学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2020
·
IF 7.577
Fangjing Lin,Jianteng Sun,Na Liu,Lizhong Zhu
Polychlorinated biphenyls (PCBs) and their biotransformation products, hydroxylated (OH-PCBs) and methoxylated derivatives (MeO-PCBs), have been detected in the environment and biota, especially crops. However, to date, little information is available on the phytotoxicity and metabolic responses induced by these chemicals in crops. In this study, we exposed rice ( Oryza sative L.) seedlings to 2,3,4,5-tetrachlorobiphenyl (CB-61) and its hydroxylated (4′-OH-CB-61) and methoxylated derivatives (4′-MeO-CB-61) at 0, 10, 50, 100 and 500 μg/L, respectively. After exposure for 14 days, significantly growth inhibition and oxidative damage were observed, among which the toxicities of 4′-OH-CB-61 and 4′-MeO-CB-61 were greater than that of the parent PCBs. Metabolomics analysis indicated that exposure to the three chemicals induced different metabolic responses. 4′-MeO-CB-61 mainly affected the saccharide catabolism, including pyruvate metabolism, the TCA cycle, the transfer of acetyl groups into mitochondria and the Warburg effect, resulting in a greater energy consumption. Moreover, both CB-61 and 4′-OH-CB-61 promoted several amino acid metabolism and fatty acid biosynthesis, thereby alleviating the potential ROS damage. This study for the first time evaluates and reveals the phytotoxicity of OH-PCBs and MeO-PCBs at the metabolic level, which attempts to provide important information for accurately evaluating the environmental risks of PCBs from the perspective of metabolism.
研究领域:
环境科学
·
植物生物学
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毒理学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）