Amino AcidsPub Date : 2026-03-07DOI: 10.1007/s00726-026-03502-8
Xinya Zhang, Wenkai Wang, Le Yang, Ye Sun, Hui Sun, Xueping Zhao, Hui Sun, Guangli Yan, Xijun Wang
{"title":"Targeting amino acid metabolic pathways: a novel therapeutic strategy for hyperuricemia-associated complications","authors":"Xinya Zhang, Wenkai Wang, Le Yang, Ye Sun, Hui Sun, Xueping Zhao, Hui Sun, Guangli Yan, Xijun Wang","doi":"10.1007/s00726-026-03502-8","DOIUrl":"10.1007/s00726-026-03502-8","url":null,"abstract":"<div><p>Hyperuricemia (HUA) is a metabolic disorder that contributes to the pathogenesis of gout arthritis (GA), chronic kidney disease (CKD), and cardiovascular disease (CVD). While current urate-lowering therapies effectively reduce serum uric acid levels, they fail to address the underlying metabolic dysregulation driving HUA progression and associated tissue damage. Emerging evidence highlights that dysregulated amino acid (AA) metabolism in bone, kidney, and vascular tissues plays a pivotal role in HUA-related complications. This review synthesizes recent advances in understanding AA metabolic pathways involved in HUA complications and elucidates the therapeutic potential of targeting tissue-specific AA metabolism. We propose precision modulation of AA metabolism as a promising strategy for both preventing and treating HUA-associated complications.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-026-03502-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2026-03-05DOI: 10.1007/s00726-026-03507-3
Huan Zhang, Wei Ye, Lingzhi Zeng, Lu Wang, Ling Gui
{"title":"Amino acid metabolism-related model for prognosis and immunity in gastric cancer","authors":"Huan Zhang, Wei Ye, Lingzhi Zeng, Lu Wang, Ling Gui","doi":"10.1007/s00726-026-03507-3","DOIUrl":"10.1007/s00726-026-03507-3","url":null,"abstract":"<div><p>Amino acid metabolic (AAM) reprogramming is a key characteristic of gastric cancer (GC) cells metabolic remodeling, which regulates cell growth, survival, immune cell activation and function to affect tumor immune escape. This study aims to systematically investigate AAM reprogramming in gastric cancer (GC) and construct prognostic model, and validate gene signatures for predictive value and clinical decision-making. This study leveraged data from TCGA and GEO to construct a prognostic model related to AAM and assess its clinical relevance in GC. We identified differentially expressed genes and conducted GO, GSEA, and GSVA enrichment analyses, along with constructing PPI networks and interaction networks of mRNA-miRNA, mRNA-TF, and mRNA-RBP. Additionally, immune infiltration analysis was performed and the relationships between eight hub-type amino acid metabolism-related genes (AAMRGs) and immune cells was investigated using scRNA-seq datasets. Lastly, we validated the elevated expression of these eight genes in GC cells through PCR. The study constructed a prognostic model for GC based on AAMRGs, identifying 16 key genes: ACLY, ADH4, COL1A1, F2, GADL1, GAMT, HBB, KYNU, MRI1, MTHFR, NR1D1, PDK4, SLC1A7, SLC25A15, SLC52A3, and SYCE2. Statistical analysis showed that 14 of these genes showed significant differential expression between tumor and normal tissues. Furthermore, the model demonstrated strong correlations with OS outcomes. Immune infiltration analysis indicated that various immune cell types were significantly associated with the expression of 8 hub genes, highlighting their potential role in the tumor microenvironment and immune response modulation. Furthermore, elevated expression of these genes in GC cells was validated through PCR, highlighting their relevance as potential biomarkers and therapeutic targets. Our AAMRGs prognostic model reveals AAMRGs as independent prognostic factors for GC, highlighting their association with prognosis and immune cell infiltration. These findings provide important insights for improving survival outcomes and advancing immunotherapy strategies in GC.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-026-03507-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2026-03-05DOI: 10.1007/s00726-026-03506-4
Shinsuke Fujiwara, Wakao Fukuda
{"title":"Branched-chain polyamines: evolutionary adaptation and biotechnological potential","authors":"Shinsuke Fujiwara, Wakao Fukuda","doi":"10.1007/s00726-026-03506-4","DOIUrl":"10.1007/s00726-026-03506-4","url":null,"abstract":"<div><p>Branched-chain polyamines (BCPAs), exemplified by <i>N</i>⁴-bis(aminopropyl)spermidine, are distinctive polycations that occur predominantly in thermophilic bacteria and euryarchaeal archaea. Their dedicated aminopropyltransferase, BpsA (EC 2.5.1.128), extends spermidine into branched architectures via sequential decarboxylated <i>S</i>-adenosylmethionine (dcSAM)-dependent reactions. Accumulated evidence demonstrates that BCPAs engage nucleic acids with substantially higher affinity than linear polyamines such as spermidine, and they uniquely induce strong DNA compaction accompanied by B→A→C structural transitions. These interactions greatly enhance the resistance of DNA to thermal, chemical, and physical damage. Genetic and physiological analyses in <i>Thermococcus kodakarensis</i> further show that loss of BCPA biosynthesis compromises growth at very high temperatures, disrupts temperature- and membrane-associated stress responses, and alters transcriptional and translational regulation; intriguingly, the linear tetraamine thermospermine can partially substitute for BCPA in several of these functions. Beyond cellular physiology, immobilized BCPAs enable sensitive nucleic-acid capture and direct PCR and isothermal DNA amplification from highly dilute solutions, demonstrating their potential utility in molecular diagnostics and environmental DNA workflows. This review synthesizes current knowledge of BCPA distribution, biosynthesis, structure–function relationships, cellular roles, and emerging biotechnological applications, and highlights key open questions in the field.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-026-03506-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tryptophan metabolism reprogramming regulates Th1/Th2 immune balance and inhibits mast cell activation","authors":"Dongsheng Huang, Dongxuan Huang, Lianhui Su, Chaowen He, Xiaopeng Zhang, Jianfeng Peng, Lumei Fan, Yahui Cao, Licheng Chen, Huifen Tong","doi":"10.1007/s00726-026-03508-2","DOIUrl":"10.1007/s00726-026-03508-2","url":null,"abstract":"<div><p>Asthma is characterized by chronic airway inflammation and an imbalanced Th1/Th2 response. Although tryptophan metabolism has been implicated in immune regulation, its direct influence on Th1/Th2 differentiation and mast-cell activation remains insufficiently understood. CD4⁺ T cells were cultured under graded tryptophan concentrations (25, 50, 75 and 100 µM) to examine how tryptophan availability alters Th1/Th2 polarization. Flow cytometry, western blotting and RT-qPCR were used to evaluate phenotype markers and related metabolic pathways. In parallel, IgE-activated LAD2 mast cells were exposed to different tryptophan concentrations with or without the IDO1/TDO inhibitor HY-149,411, followed by immunofluorescence staining and ELISA to assess tryptase expression and histamine release. High tryptophan availability markedly enhanced Th1 differentiation, with increased Notch1/Jagged1 levels and elevated IL-2 and IFN-γ, while IL-4 expression was reduced. RT-qPCR showed upregulated T-bet and mTOR and downregulated GATA3, together with increased IDO1 and TDO mRNA levels in CD4⁺ T cells, indicating Th1-biased immunometabolic activation. In mast cells, tryptophan treatment suppressed tryptase expression and lowered histamine secretion, demonstrating reduced activation. HY-149,411 attenuated tryptophan-dependent differences in histamine release, suggesting that tryptophan catabolism contributes to mast-cell regulation. Tryptophan availability reprograms immune metabolism to promote Th1 differentiation and suppress mast-cell activation, offering a dual mechanism through which tryptophan may help correct Th1/Th2 imbalance and ameliorate allergic inflammation. These findings highlight tryptophan metabolism as a potential immunometabolic target for asthma therapy.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-026-03508-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2026-02-21DOI: 10.1007/s00726-026-03505-5
Tushar Adhikari, Prerona Saha
{"title":"Probiotic and microbial modulation of polyamine production: an emerging avenue for neuroprotection in neurodegenerative disorders","authors":"Tushar Adhikari, Prerona Saha","doi":"10.1007/s00726-026-03505-5","DOIUrl":"10.1007/s00726-026-03505-5","url":null,"abstract":"<div><p>Neurodegenerative disorders are an Critical worldwide issue, characterized by progressive neuronal loss and cognitive decline with limited effective therapies. A central problem in these conditions is chronic neuroinflammation, oxidative stress, and disrupted cellular homeostasis. Polyamines, such as putrescine, spermidine, and spermine—small molecules—play vital roles in maintaining neuronal function, regulating autophagy, and protecting against cellular stress. Notably, spermidine-induced autophagy has emerged as a key mechanism linking polyamine metabolism to neuronal longevity and cognitive resilience. Recent studies highlight that probiotics and specific gut microbes can effectively modulate host polyamine production through the gut-brain axis, influencing neural health. This microbial modulation has been shown to restore polyamine balance, enhance antioxidant defenses, and reduce neuroinflammatory responses. Targeting microbiota-driven polyamine synthesis is emerging as a promising, non-invasive approach for neuroprotection. This review consolidates the current understanding of polyamine biology and microbial influences, highlighting their therapeutic potential. Exploring these interactions offers new avenues for innovation in combatting neurodegenerative disorders.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-026-03505-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2026-02-13DOI: 10.1007/s00726-025-03470-5
Hinpetch Daungsupawong, Viroj Wiwanitkit
{"title":"Association of homoarginine with arginine and disease severity in COVID-19 patients: comment","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1007/s00726-025-03470-5","DOIUrl":"10.1007/s00726-025-03470-5","url":null,"abstract":"","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12904975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2026-02-12DOI: 10.1007/s00726-026-03504-6
Armando A. Puente, Lyra Kinderlerer, Luna J. Castillo, Raghavendra G. Mirmira, Sarah A. Tersey
{"title":"Using animal models to decipher the role of polyamines in the pancreas and β Cell","authors":"Armando A. Puente, Lyra Kinderlerer, Luna J. Castillo, Raghavendra G. Mirmira, Sarah A. Tersey","doi":"10.1007/s00726-026-03504-6","DOIUrl":"10.1007/s00726-026-03504-6","url":null,"abstract":"<div><p>Pancreatic islet β cells are insulin-secreting cells that are responsible for sensing blood glucose levels and maintaining normoglycemia. Polyamines are vital to supporting the transcriptional and translational demands placed on secretory cells such as the β cell; however, recent evidence suggests the polyamine pathway may also be detrimental to normal β cell function. β cell dysfunction instigated by inflammation is common to both type 1 and type 2 diabetes, and notably, interventions that target the polyamine pathway may offer therapeutic benefits. The objective of this review is to synthesize the roles of polyamine metabolism in the pancreas and to frame this pathway as a link between nutrient status, immune activation, and β cell stress in diabetes. This review summarizes key findings from animal models used to study the polyamine pathway in pancreatic islet growth, development, and function. It also explores the prospects of polyamine inhibition to modify diabetes pathogenesis and improve β cell health.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Solid-state cultivation-specific agmatine production by Aspergillus oryzae: current understanding and perspectives","authors":"Naoki Akasaka, Daisuke Watanabe, Kiyoshi Yasukawa, Shinsuke Fujiwara","doi":"10.1007/s00726-026-03503-7","DOIUrl":"10.1007/s00726-026-03503-7","url":null,"abstract":"<div><p>Agmatine, a natural polyamine generated from arginine by arginine decarboxylase (ADC), has attracted increasing attention because of its pleiotropic beneficial effects on neuroprotection, lifestyle-related diseases, and gut-brain axis-mediated pathways. Although mammals appear to possess only limited capacity to synthesize endogenous agmatine, accumulating evidence suggests that agmatine derived from diet and the gut microbiota contributes to systemic levels of this polyamine. Previous studies have revealed that <i>Aspergillus oryzae</i>, the filamentous fungus foundational to traditional Japanese cuisine and indispensable for starch saccharification in sake, miso, soy sauce, mirin, and other fermented foods, produces high levels of agmatine specifically under solid-state cultivation. Subsequent studies identified a novel pyruvoyl-dependent ADC (<i>Ao</i>-ADC1) responsible for this unique agmatine production. This mini-review summarizes current knowledge on solid-state cultivation-specific agmatine production by <i>A. oryzae</i>, with a particular focus on the discovery and biochemical characteristics of <i>Ao</i>-ADC1. These findings challenge the commonly accepted notion that ascomycetes lack ADC. Understanding the molecular rationale and physiological significance of this unique agmatine biosynthetic pathway provides a foundation for rational strategies to enhance agmatine production in <i>A. oryzae</i> and for the development of agmatine-enriched fermented foods and nutraceuticals. Furthermore, integrating this fungal pathway with emerging insights into microbe-host interactions may further illuminate how fermentation-derived agmatine contributes to human health through gut-brain axis mediated mechanisms.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12904898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2026-02-07DOI: 10.1007/s00726-026-03499-0
Izabela Zakrocka, Radosław Mlak, Natalia Moniczewska, Sylwia Boczkowska, Renata Kloc, Tomasz Kocki, Ewa M. Urbańska, Wojciech Załuska, Andreas Kronbichler
{"title":"Tryptophan metabolites clearance in hemodialyzed patients","authors":"Izabela Zakrocka, Radosław Mlak, Natalia Moniczewska, Sylwia Boczkowska, Renata Kloc, Tomasz Kocki, Ewa M. Urbańska, Wojciech Załuska, Andreas Kronbichler","doi":"10.1007/s00726-026-03499-0","DOIUrl":"10.1007/s00726-026-03499-0","url":null,"abstract":"<div><p>Hemodialysis (HD) and hemodiafiltration (HDF) procedures have limited efficacy regarding removal of selected toxins. Tryptophan (Trp) metabolites formed through the kynurenine (KYN) pathway are known to contribute to kidney failure (KF) complications, some of which may affect the survival of neurons. The aim of this study was to investigate the removal of Trp and its metabolites, KYN, kynurenic acid (KYNA) and 3-hydroxykynurenine (3-OHKYN) in patients treated by HD or HDF and the impact of patients’ comorbidities on toxins removal. The study was conducted in 50 patients with KF. Serum level of free fractions of Trp and its metabolites were measured before and after a dialysis session through high performance liquid chromatography. The serum concentration of Trp, as well as 3-OHKYN/KYN ratio remained unchanged, whereas the concentration of KYN, KYNA, 3-OHKYN, together with KYN/Trp ratio significantly decreased after dialysis procedures. The indices KYNA/KYN and KYNA/3-OHKYN increased. In patients with heart failure, higher reduction ratio (RR) of KYN was found, whereas in patients with diabetes higher KYN RR and lower KYNA RR was observed. In patients without residual kidney function, KYNA RR was significantly higher compared to patients with preserved diuresis. RR of all tested metabolites did not differ between HD and HDF treated patients. In KF, Trp metabolites were removed from the blood during dialysis procedures with different efficacies. Targeted strategies to lower KYN pathway metabolites concentration may be beneficial in patients with KF and selected comorbidities.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12904910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amino AcidsPub Date : 2026-02-06DOI: 10.1007/s00726-026-03501-9
Rashmi Tupe, Ankita Durge, Ashwini Jagdale
{"title":"Unveiling the anti-glycation properties of acetylsalicylic acid: targeted inhibition of albumin glycation","authors":"Rashmi Tupe, Ankita Durge, Ashwini Jagdale","doi":"10.1007/s00726-026-03501-9","DOIUrl":"10.1007/s00726-026-03501-9","url":null,"abstract":"<div><p>Glycation due to increased blood sugar levels aggravates diabetic complications. Glycation hampers the structural and functional integrity of human serum albumin (HSA). Acetylsalicylic acid (ASA)/aspirin exhibits anti-glycation properties. Although the precise molecular mechanism of ASA in glycation has not yet been conclusively demonstrated, acetylation has been considered the central mechanism underlying its biological action. The present study aims to unveil the specific mechanism of action of ASA on glycated HSA through meticulously designed approaches. Fluorescence and UV-visible spectroscopy were used to analyse glycation adducts in the presence of ASA. ANS-based fluorescence spectroscopy, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, and high-performance liquid chromatography were used to study the structural modifications of glycated HSA in the presence of ASA. Furthermore, we investigated functional modifications in glycated HSA using nuclear magnetic resonance spectroscopy. The analyzed data showed a direct association between glycation and the impaired structural and functional integrity of HSA, which was partially restored by ASA. Our data corroborate that ASA’s prominent anti-glycation activity may be attributable to mechanisms other than acetylation.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12904887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}