Amino acid metabolism in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 13, 2023

Abstract Amino acids are the building blocks of protein synthesis. They structural elements and energy sources cells necessary for normal cell growth, differentiation function. acid metabolism disorders have been linked with a number pathological conditions, including metabolic diseases, cardiovascular immune cancer. In case tumors, alterations in amino can be used not only as clinical indicators cancer progression but also therapeutic strategies. Since growth development tumors depend on intake foreign acids, more studies targeted tumor-related to selectively kill tumor cells. Furthermore, immune-related confirmed that regulates function effector T regulatory cells, affecting Therefore, studying associated disease identifying targets pathways may helpful treatment. This article mainly focuses research tumor-oriented reviews progress diseases related metabolism, order provide theoretical basis therapy metabolism.

Language: Английский

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Glutamine Is Required for M1-like Polarization of Macrophages in Response to Mycobacterium tuberculosis Infection

mBio, Journal Year: 2022, Volume and Issue: 13(4)

Published: June 28, 2022

Macrophages play essential roles in determining the progression and final outcome of human infection by Mycobacterium tuberculosis . While upregulation hypoxia-inducible-factor 1 (HIF-1) a metabolic reprogramming to Warburg Effect-like state are known be critical for immune cell activation response M. infection, our overall knowledge about immunometabolism M1-like macrophages is poor.

Language: Английский

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The causes and consequences of trained immunity in myeloid cells

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 11, 2024

Conventionally, immunity in humans has been classified as innate and adaptive, with the concept that only latter type an immunological memory/recall response against specific antigens or pathogens. Recently, a new of trained (a.k.a. memory response) emerged. According to this concept, immune cells can exhibit enhanced responsiveness subsequent challenges, after initial stimulation antigen/pathogen. Thus, enables respond robustly non-specifically through exposure re-exposure antigens/infections vaccines, providing resistance unrelated pathogens reduced infection severity. For example, individuals vaccinated BCG protect tuberculosis were also protected from malaria SARS-CoV-2 infections. Epigenetic modifications such histone acetylation metabolic reprogramming (e.g. shift towards glycolysis) their inter-linked regulations are key factors underpinning activation cells. The integrated epigenetic rewiring generates sufficient intermediates, which is crucial meet energy demand required produce proinflammatory antimicrobial responses by These determine efficacy durability immunity. Importantly, signaling pathways regulatory molecules be harnessed potential targets for developing novel intervention strategies, better vaccines immunotherapies infectious (e.g., sepsis) non-infectious cancer) diseases. However, aberrant inflammation caused inappropriate onset lead severe autoimmune pathological consequences, systemic sclerosis granulomatosis). In review, we provide overview conventional adaptive summarize various mechanistic associated regulation immunity, focusing on immunologic, metabolic, changes myeloid This review underscores transformative immunology, paving way therapeutic strategies diseases leverage memory.

Language: Английский

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Phenylalanine diminishes M1 macrophage inflammation

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(12), P. 2862 - 2876

Published: May 25, 2023

Language: Английский

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Sulfur metabolic response in macrophage limits excessive inflammatory response by creating a negative feedback loop

Redox Biology, Journal Year: 2023, Volume and Issue: 65, P. 102834 - 102834

Published: July 29, 2023

The excessive inflammatory response of macrophages plays a vital role in the pathogenesis various diseases. dynamic metabolic alterations macrophages, including amino acid metabolism, are known to orchestrate their phenotype. To explore new pathway that regulates response, we examined metabolome changes mouse peritoneal (PMs) lipopolysaccharide (LPS) and found coordinated increase cysteine its related metabolites, suggesting an enhanced demand for during response. Because Slc7a11, which encodes cystine transporter xCT, was remarkably upregulated upon pro-inflammatory challenge serve as major channel supply, behavior Slc7a11 knockout PMs (xCT-KO PMs) clarify impact increased on inflammation. xCT-KO exhibited prolonged upregulation genes, recapitulated by depletion culture media wild-type PMs, facilitates resolution Detailed analysis sulfur revealed supersulfides, such persulfide, were LPS, abolished PMs. Supplementation N-acetylcysteine tetrasulfide (NAC-S2), supersulfide donor, attenuated gene expression Thus, activated uptake via xCT produce creating negative feedback loop limit Our study highlights finely tuned regulation macrophage metabolism.

Language: Английский

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Metabolic rewiring and communication in cancer immunity

Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(5), P. 862 - 883

Published: Feb. 29, 2024

The immune system shapes tumor development and progression. Although immunotherapy has transformed cancer treatment, its overall efficacy remains limited, underscoring the need to uncover mechanisms improve therapeutic effects. Metabolism-associated processes, including intracellular metabolic reprogramming intercellular crosstalk, are emerging as instructive signals for anti-tumor immunity. Here, we first summarize roles of pathways in controlling cell function microenvironment. How communication regulates immunity, impact metabolites or nutrients on signaling events, also discussed. We then describe how targeting cells intratumoral via nutrient-based interventions may boost immunotherapies. Finally, conclude with discussions profiling functional perturbation methods activity cells, perspectives future directions. Uncovering rewiring microenvironment enable novel

Language: Английский

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Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(8), P. 3025 - 3040

Published: April 3, 2024

Despite the recent and increasing knowledge surrounding COVID-19 infection, underlying mechanisms of persistence symptoms for a long time after acute infection are still not completely understood. Here, multiplatform mass spectrometry-based approach was used metabolomic lipidomic profiling human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered mild 40). Untargeted analysis using CE-ESI(+/−)-TOF-MS GC-Q-MS performed. Additionally, LC-ESI(+/−)-QTOF-MS based on an in-house library revealed 447 lipid species identified high confidence annotation level. The integration complementary analytical platforms has allowed comprehensive metabolic characterization alterations in disease that found 46 relevant metabolites which discriminate between patients. We report specific altered COVID, mainly related decrease amino acid metabolism ceramide levels increase tricarboxylic (TCA) cycle, reinforcing evidence impaired function. most shown this study will help better understand insights syndrome by providing deeper basis pathology.

Language: Английский

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Cellular metabolism changes in atherosclerosis and the impact of comorbidities

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Aug. 12, 2024

Cell activation and nutrient dysregulation are common consequences of atherosclerosis its preceding risk factors, such as hypertension, dyslipidemia, diabetes. These diseases may also impact cellular metabolism consequently cell function, the other way around, altered can disease development progression through function. Understanding contribution to how be by co-morbidities factors could support novel strategies lower CVD. Therefore, we briefly review pathogenesis principles metabolic pathways, before detailing changes in context comorbidities. In hypoxic, inflammatory hyperlipidemic milieu atherosclerotic plaque riddled with oxidative stress, shifts increase anaerobic glycolysis, pentose-phosphate pathway amino acid use. We elaborate on for macrophages, neutrophils, vascular endothelial cells, smooth muscle cells lymphocytes Since causal relationships specific key genes a type-specific comorbidity-dependent, cell-specific must thoroughly explored vivo , focus systemic effects. When treatments become feasible, this information will crucial determining best intervention improve interplay co-morbidities.

Language: Английский

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The gut microbiome across the cardiovascular risk spectrum

European Journal of Preventive Cardiology, Journal Year: 2023, Volume and Issue: 31(8), P. 935 - 944

Published: Dec. 7, 2023

Despite treatment advancements, cardiovascular disease remains a leading cause of death worldwide. Identifying new targets is crucial for enhancing preventive and therapeutic strategies. The gut microbiome has been associated with coronary artery (CAD), however our understanding specific changes during CAD development limited. We aimed to investigate in participants without clinically manifest different risk levels patients ST-elevation myocardial infarction (STEMI).

Language: Английский

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Investigating intestinal epithelium metabolic dysfunction in celiac disease using personalized genome-scale models

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 21, 2025

Celiac disease (CeD) is an autoimmune condition characterized by aberrant immune response triggered the ingestion of gluten, which damages epithelial cells lining small intestine. Small intestinal (sIECs) play key roles in enzymatic digestion and absorption nutrients, maintaining gut barrier integrity, regulating response. Chronic inflammation tissue damage associated with CeD disrupt intricate network metabolic processes sIECs that support these functions, impairing their ability to perform essential roles. However, specific disrupted underlying dysfunction remain largely undefined. To address this knowledge gap, personalized, sex-specific genome-scale models metabolism were constructed using transcriptional data from biopsies 42 subjects active CeD, remission (on a gluten-free diet), non-CeD controls. These computationally simulated under relevant dietary conditions for each group assess activity several tasks function profile metabolite secretion into bloodstream lumen. Significant alterations 28 observed impacting critical integral such as oxidative stress regulation, nucleotide synthesis DNA repair, energy production, polyamine amino acid metabolism. Additionally, altered profiles metabolites, encompassing acids, vitamins, polyamines, lipids, fatty detected patients. findings partially supported comparisons independent external datasets further corroborated through extensive review existing literature. Furthermore, drug target analysis was performed, identifying 22 FDA-approved drugs genes encoding impaired functions potentially helping restore normal activity. This study unveils new insights reprogramming highlighting dysregulated compromise cellular health. offer foundation developing therapeutic interventions targeting CeD.

Language: Английский

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