Amino AcidsPub Date : 2026-02-02Epub Date: 2026-05-22DOI: 10.1007/s00726-026-03496-3
Alain P. Gobert, Kara M. McNamara, Caroline V. Hawkins, Mohammad Asim, Daniel P. Barry, Alberto G. Delgado, Kristie L. Rose, Purvi Patel, Regina N. Tyree, Kate S. Carson, Lori A. Coburn, M. Blanca Piazuelo, Keith T. Wilson
{"title":"Epithelial hypusination regulates Helicobacter pylori-induced gastric inflammation","authors":"Alain P. Gobert, Kara M. McNamara, Caroline V. Hawkins, Mohammad Asim, Daniel P. Barry, Alberto G. Delgado, Kristie L. Rose, Purvi Patel, Regina N. Tyree, Kate S. Carson, Lori A. Coburn, M. Blanca Piazuelo, Keith T. Wilson","doi":"10.1007/s00726-026-03496-3","DOIUrl":"10.1007/s00726-026-03496-3","url":null,"abstract":"<div><p>Hypusine is a unique amino acid synthesized on the eukaryotic initiation factor 5 A (EIF5A) from the polyamine spermidine by deoxyhypusine synthase (DHPS). Hypusination of EIF5A plays a key role in translation. Here, we examined the contribution of the epithelial hypusination pathway to gastric inflammation induced by <i>Helicobacter pylori</i>. Immunohistochemical analyses revealed increased expression of DHPS and hypusinated EIF5A (EIF5A<sup>Hyp</sup>) in the gastric mucosa of patients with <i>H. pylori</i> gastritis compared to uninfected individuals, notably within gastric epithelial cells (GECs) and immune infiltrates. Then, we created a mouse model with epithelial-specific deletion of Dhps (<i>Dhps</i><sup><i>Δepi</i></sup>) and confirmed the reduction of DHPS and EIF5A<sup>Hyp</sup> in GECs. <i>H. pylori</i>-infected <i>Dhps</i><sup><i>Δepi</i></sup> mice exhibited an attenuation of gastric histologic inflammation scores compared with infected <i>Dhps</i><sup><i>fl/+</i></sup> controls, without alteration in bacterial colonization levels. Quantitative proteomics of isolated GECs showed that <i>Dhps</i> deletion altered the expression of proteins involved in organismal injury, cancer, and gastrointestinal diseases in naïve mice. Upon <i>H. pylori</i> infection, inflammatory and immune response proteins, including signaling factors and immunoglobulin mediators, were less induced in <i>Dhps</i><sup><i>Δepi</i></sup> GECs, and pathways linked to tissue injury and inflammation were selectively downregulated. Together, these findings demonstrate that epithelial hypusination supports <i>H. pylori</i>-driven gastric inflammation without affecting bacterial persistence. Targeting DHPS-dependent EIF5A hypusination may thus represent a novel therapeutic strategy to limit <i>H. pylori</i>-associated mucosal injury and disease progression.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103458","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 : 2026-02-02DOI: 10.1007/s00726-026-03498-1
Barbara Reischl, Benjamin Schupp, Christian Fink, Simon K.-M. R. Rittmann
{"title":"Quantitative analysis of amino acid excretion and consumption by Methanothermobacter marburgensis in fed-batch cultivation mode","authors":"Barbara Reischl, Benjamin Schupp, Christian Fink, Simon K.-M. R. Rittmann","doi":"10.1007/s00726-026-03498-1","DOIUrl":"10.1007/s00726-026-03498-1","url":null,"abstract":"<div><p>The methanogenic archaeon <i>Methanothermobacter marburgensis</i> offers a promising alternative to traditional bacterial systems for the sustainable production of proteinogenic amino acids (AAs), eliminating the need for sugar-based feedstock. In this study, we quantitatively examined AA excretion and consumption in fed-batch cultivation mode in bioreactors under varying ammonium (NH<sub>4</sub><sup>+</sup>) concentrations and gas compositions. <i>M. marburgensis</i> demonstrated excretion of a wide spectrum of AAs with distinct profiles shaped by nitrogen availability. While high NH<sub>4</sub><sup>+</sup> concentrations suppressed total AA excretion, NH<sub>4</sub><sup>+</sup> limited conditions triggered alanine accumulation followed by its re-assimilation, suggesting a regulatory mechanism linked to nitrogen stress. Moreover, carbon limitation and nitrogen excess resulted in the production of an AA pattern including asparagine. Despite lower overall productivity compared to engineered bacterial strains, <i>M. marburgensis</i> exhibited the unique ability to simultaneously excrete multiple AAs without requiring organic carbon input. These findings advance the feasibility of using methanogens for AA bioprocessing and the development of archaea as next-generation microbial cell factories.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12881071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103478","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 : 2026-02-01DOI: 10.1007/s00726-026-03500-w
Abdilatif Aynaashe, Petri Kursula
{"title":"Genetic commonalities between rare subtypes of ALS and CMT: insights into molecular mechanisms of neurodegeneration","authors":"Abdilatif Aynaashe, Petri Kursula","doi":"10.1007/s00726-026-03500-w","DOIUrl":"10.1007/s00726-026-03500-w","url":null,"abstract":"<div><p>Amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth disease (CMT) are two distinct neurodegenerative disorders. While ALS is characterised by rapidly progressive motor neuron degeneration, leading to severe complications and death, CMT as a peripheral neuropathy is less severe, and patients have a longer life span, although with a compromised quality of life. Despite their clinical differences, current knowledge suggests that familial ALS (fALS) and CMT may share common genetic and molecular mechanisms. We aimed to identify shared genes mutations and molecular pathways between fALS and CMT through a literature and database search. Thirteen genes were identified, involved in distinct cellular processes: axonal transport (<i>DYNC1H1</i>,<i> KIF5A</i>,<i> SPG11</i>, <i>DCTN1</i>), protein homeostasis (<i>NEFH</i>,<i> VCP</i>,<i> SOD1</i>), RNA metabolism (<i>GARS</i>,<i> SETX</i>), cellular stress response (<i>HSPB1</i>,<i> FIG4</i>), and mitochondrial function (<i>MFN2</i>, <i>CHCHD10</i>). While these linkages to the two diseases are rare for each gene, understanding possible mechanistic commonalities at the molecular level can initiate new research directions, help in identifying additional common genes between neurodegenerative disorders, and improve diagnostics.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12881070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100024","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 : 2026-01-31DOI: 10.1007/s00726-026-03497-2
Takeshi Uemura, Jun Takayama, Akihiro Oguro, Yusuke Terui
{"title":"Polyamine metabolism as a regulator of cellular and organismal aging","authors":"Takeshi Uemura, Jun Takayama, Akihiro Oguro, Yusuke Terui","doi":"10.1007/s00726-026-03497-2","DOIUrl":"10.1007/s00726-026-03497-2","url":null,"abstract":"<div><p>Polyamines - putrescine, spermidine, and spermine - are ubiquitous cationic molecules that are essential for cellular proliferation and homeostasis. Their intracellular concentrations decline with age, contributing to physiological and cognitive deterioration. Recent studies have revealed that spermidine supplementation extends lifespan and improves cognitive and cardiac function in various model organisms, suggesting that maintaining polyamine balance has anti-aging potential. Polyamine metabolism is tightly regulated through biosynthesis, degradation, and transport; however, age-associated upregulation of spermine oxidase (SMOX) and accumulation of its toxic byproduct acrolein promote oxidative damage and cellular senescence. Suppressing SMOX activity or polyamine degradation attenuates senescence markers and DNA damage, highlighting spermine catabolism as a therapeutic target. Polyamines also modulate epigenetic regulation, including DNA methylation and histone acetylation, thereby influencing gene expression and chromatin structure during aging. Moreover, polyamine-dependent hypusination of eIF5A sustains protein synthesis in senescent cells. These multifaceted actions indicate that polyamine metabolism integrates redox control, translational regulation, epigenetic maintenance and autophagy to determine cellular and organismal longevity. While animal studies demonstrate clear anti-aging effects of spermidine and spermine, human clinical evidence remains limited, with variable outcomes likely due to bioavailability and metabolic conversion. Future strategies combining dietary or probiotic polyamine enhancement, enzyme-targeted inhibitors, and personalized metabolic interventions hold promise for extending healthspan. Collectively, maintaining optimal polyamine homeostasis emerges as a key approach to counteract aging and age-related diseases.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12881085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091772","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 : 2026-01-23DOI: 10.1007/s00726-025-03491-0
Connor R. Phillips, Jake P. Violi, David P. Bishop, Kenneth J. Rodgers
{"title":"Analysis of amino acids in Mucuna pruriens supplements using hydrophilic interaction liquid chromatography-tandem mass spectrometry","authors":"Connor R. Phillips, Jake P. Violi, David P. Bishop, Kenneth J. Rodgers","doi":"10.1007/s00726-025-03491-0","DOIUrl":"10.1007/s00726-025-03491-0","url":null,"abstract":"<div><p><i>Mucuna pruriens</i> (MP), or velvet bean, has been used as an alternative medicine in India for over 4500 years, predominantly due to the natural abundance of the non-protein amino acid L-3,4-dihydroxyphenylalanine (L-DOPA). L-DOPA (levodopa) is used to treat Parkinson’s disease (PD), a condition in which the progressive loss of dopaminergic neurons causes dopamine deficiency and impaired motor function. Although L-DOPA increases dopamine synthesis in the remaining dopaminergic neurones in the PD brain, the rate of disease progression appears to remain unchanged. Some studies have demonstrated improved outcomes in patients taking MP preparations compared to those undergoing traditional L-DOPA therapy. There is evidence that the canonical amino acids and L-DOPA precursors L-phenylalanine (L-Phe) and L-tyrosine (L-Tyr) can increase dopamine synthesis and also protect against the mistaken incorporation of L-DOPA into proteins during protein synthesis. The current study developed and validated a sensitive HILIC–TQMS method for the quantification of L-DOPA and related amino acids in MP preparations. Analysis revealed that L-DOPA levels were 66.2% to 82.7% of the values reported by manufacturers. Tyr and Phe were present in both free and protein bound forms in all 5 preparations analysed, potentially offering protection against the mistaken incorporation of L-DOPA into proteins and promoting increased dopamine synthesis. These findings suggest that the additional reported benefits of MP supplements for PD treatment might, in part, be attributable to the presence of these amino acids, further supporting the need to investigate the administration of L-DOPA and its cognate amino acid in symptomatic treatment of PD.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12881161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027881","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 : 2025-12-26DOI: 10.1007/s00726-025-03492-z
Babak Bakhshinejad, Andreas Kjaer
{"title":"NGS and the design of an optimized phage display workflow for peptide discovery","authors":"Babak Bakhshinejad, Andreas Kjaer","doi":"10.1007/s00726-025-03492-z","DOIUrl":"10.1007/s00726-025-03492-z","url":null,"abstract":"<div><p>Phage display is a powerful technology that has demonstrated great potential in identifying peptides with high binding affinity and specificity toward a broad spectrum of biological targets. The undesired enrichment of nonspecific binders remains a major challenge in phage display selection. The integration of next-generation sequencing (NGS) into phage display has expanded the horizons of ligand discovery by significantly enhancing our ability to interrogate the massive sequence space of combinatorial phage display libraries and providing quantitative information about their composition and evolution during biopanning. NGS findings have provided strong support for the notion that the selection output still contains a large number of nonspecifically enriched peptide sequences that could not be removed or identified by traditional strategies for biopanning optimization. Despite its great potential for increasing the strength of peptide discovery, the routine NGS-based phage display workflow, which relies on analyzing the biopanning output, fails to effectively distinguish thousands of nonspecific peptides from specific target-binding sequences. By incorporating precise control experiments—including the NGS characterization of the unamplified and amplified naïve libraries and the outputs of targetless and replicate selections—alongside the thoughtful data analysis and interpretation, we propose an optimized workflow of NGS-based phage display that would be capable of distinguishing many target-specific peptides from the overwhelming background of nonspecific binders. Applying such a systematic approach will not only advance fundamental research for peptide discovery but also hold promise for the clinic, where these peptides can serve as the foundation for next-generation diagnostic and therapeutic platforms in precision medicine.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03492-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145832977","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 : 2025-12-22DOI: 10.1007/s00726-025-03495-w
Lude Wang, Qiuwen Lou, Jie Chang, Zhijian Xu, Fan Yang, Qi Tu, Jianmin Zhang, Wenxia Xu, Minfeng Tong
{"title":"MTR4 methylation-dependent degradation activates mTORC1 signaling to promote glioma cell survival under methionine starvation","authors":"Lude Wang, Qiuwen Lou, Jie Chang, Zhijian Xu, Fan Yang, Qi Tu, Jianmin Zhang, Wenxia Xu, Minfeng Tong","doi":"10.1007/s00726-025-03495-w","DOIUrl":"10.1007/s00726-025-03495-w","url":null,"abstract":"<div>\u0000 \u0000 <p>Methionine is an essential amino acid for the human body. Understanding how tumor cells adjust their signaling networks to evade apoptosis and sustain proliferation in a methionine starvation tumor microenvironment is a significant scientific question that warrants in-depth investigation. This study aims to explore the response mechanisms of glioma under methionine starvation conditions, thereby providing a theoretical foundation for the development of novel therapeutic strategies for glioma. To investigate the response of glioma cells to a methionine starvation environment, we established methionine-starvation-tolerant cells. Our findings indicate that mRNA transporter 4 (MTR4) plays a crucial role in cellular adaptation to methionine starvation. This study employed various experimental approaches, including Western blotting, immunohistochemical staining, and colony formation assays, to validate the expression mechanism of MTR4 under methionine starvation conditions. Furthermore, transfection, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and cytoplasmic-nuclear fractionation techniques were utilized to explore the regulatory mechanism of MTR4 on solute carrier family 1 member 5 (SLC1A5). In response to methionine starvation, glioma cells exhibited a time-dependent activation of the mTOR signaling pathway. Transcriptomic analysis revealed a high expression of the methionine transporter SLC1A5, which is regulated at the mRNA level by the nuclear export factor MTR4. Under conditions of methionine starvation, MTR4 undergoes methylation, leading to its ubiquitination. Lysine Methyltransferase 2B (KMT2B) has been identified as the methyltransferase responsible for the methylation of MTR4. In summary, we propose that under conditions of methionine starvation, the enhanced methylation of MTR4 promotes its ubiquitin-mediated degradation. This process facilitates the nuclear export and expression of amino acid transporter mRNA, such as SLC1A5, leading to increased amino acid uptake, activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, and ultimately ensuring the survival of glioma cells. Our study provides new insights into the molecular mechanisms underlying glioma cell adaptation to methionine starvation.</p>\u0000 </div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802951","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":"Evaluation of the clinical characteristics and potentially prognostic factors in HER2-positive breast cancer","authors":"Liang Shi, Pei-Wen Xi, Zhi Li, Jing Wu, Xu Zhang, Lei Zhang","doi":"10.1007/s00726-025-03494-x","DOIUrl":"10.1007/s00726-025-03494-x","url":null,"abstract":"<div><p>From January 2000 to December 2019, the SEER Plus Database collecting human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR; including estrogen receptor [ER] and progesterone receptor [PR]) status for breast cancer (BC) cases. HER2-positive (HER2+) BC is an aggressive type, and HER2-targeted therapies have significantly improved the therapeutic outcome of patients. However, not every HER2+ BC patient achieves optimal benefits from current HER2-targeted therapies. Here, we conducted a detailed analysis to compare the demographic and clinic-pathological characteristics, survival, differential genes and mutations between HR+ and HR– in HER2+ BC patients. In this retrospective cohort study, Joint HR and HER2 status distributions by more than ten specific clinic-pathological characteristics were evaluated by using Pearson’s chi-squared (χ2) test. The transciptome RNA-seqencing (RNA-seq) expression data together with detailed clinic-pathological information of HER2+ BC were from The Cancer Genome Atlas (TCGA) and UCSC Xena<i>.</i> 30,482 (71.02%) patients were identified as HR+ /HER2+ BC and 12,440 (28.98%) patients were identified as HR−/HER2+ BC. HR+ /HER2+ BC patients were more likely to be younger than 50-year-old, white and infiltrating lobular carcinoma history than patients with HR−/HER2+. Patients with HR+ /HER2+ BC had lower risks of breast cancer-specific death and higher overall survival rates. Mast cells were enriched in the HR+ /HER2+ BC group, while plasma cells were more abundant in the HR–/HER2+ BC group.In conclusion, HER2+ BC patients benefit differently from current HER2-directed therapies, maybe partly due to the HR status and gene mutations, and they may provide potentially prognostic and predictive value and new treatment strategies for clinicians.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03494-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762086","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 : 2025-11-23DOI: 10.1007/s00726-025-03493-y
Tuğçe Deniz Karaca, Hüseyin Balcı, Arzu Aysan, Yusuf Sert, Alev Doğan
{"title":"Evaluation of the antimicrobial-cytotoxic activities and molecular docking study of L-cysteine ethyl ester and L-cysteine methyl ester","authors":"Tuğçe Deniz Karaca, Hüseyin Balcı, Arzu Aysan, Yusuf Sert, Alev Doğan","doi":"10.1007/s00726-025-03493-y","DOIUrl":"10.1007/s00726-025-03493-y","url":null,"abstract":"<div><p>Antibiotic resistance is a growing problem in the treatment of life-threatening diseases. Recently, a variety of covalent drugs have emerged. Cysteine is one of the least abundant amino acids in the proteins of many organisms, and the thiol group in its structure makes it unique and has become a common covalent amino acid residue in covalent drug development. Therefore, it is important to conduct research on cysteine derivatives. In this study, the in vitro antibacterial activity of L-cysteine esters were tested against Gram-positive <i>Staphylococcus aureus</i> and Gram-negative <i>Escherichia coli</i> using the modified microdilution broth method. In vitro cytotoxic activities of the esters were carried out against the healthy HEK293T cell line and well-differentiated liver cancer cell lines PLC/PRF/5 and HEP3B at different concentrations by using an MTS assay. In addition, molecular docking studies, ADMET properties, and drug-likeness were also reported. The results obtained are new and it is thought that these results of the study will contribute to the development of new synthesizable cysteine-based drugs. In conclusion, a thorough examination of the frontier orbital (HOMO and LUMO) and MEP studies was conducted using quantum chemistry techniques to determine the molecule’s reactivity, electrophilic and nucleophilic sites.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585801","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 : 2025-11-21DOI: 10.1007/s00726-025-03490-1
Mohadeseh Mahmoudi Ghehsareh, Sajjad Bakhtiari, Nastaran Asri, Mostafa Rezaei-Tavirani, Somayeh Jahani-Sherafat, Andrea Masotti, Mohammad Rostami-Nejad
{"title":"Impacts of conditionally essential amino acids, cysteine, and tyrosine on intestinal inflammation in celiac disease","authors":"Mohadeseh Mahmoudi Ghehsareh, Sajjad Bakhtiari, Nastaran Asri, Mostafa Rezaei-Tavirani, Somayeh Jahani-Sherafat, Andrea Masotti, Mohammad Rostami-Nejad","doi":"10.1007/s00726-025-03490-1","DOIUrl":"10.1007/s00726-025-03490-1","url":null,"abstract":"<div><p>Celiac disease (CD) is a chronic autoimmune disorder characterized by gluten-induced intestinal inflammation, epithelial barrier dysfunction, and malabsorption of nutrients, including amino acids (AAs). While essential AAs have been extensively studied, the roles of conditionally essential amino acids (CEAAs), cysteine (Cys), and tyrosine (Tyr) in CD pathogenesis remain comparatively underexplored. This review synthesizes current evidence on the contributions of these AAs to intestinal barrier integrity, immune regulation, oxidative stress mitigation, and gut microbiota modulation in CD. Key findings indicate that asparagine (Asn), glycine (Gly), Cys, glutamate (Glu), aspartate (Asp), and glutamine (Gln) contribute to the reinforcement of intestinal barrier integrity. In parallel, Cys and Gly, along with Gln and Asp, play important roles in suppressing oxidative stress, while Gln and Asp have been shown to positively influence the composition and function of the gut microbiota. Serine (Ser) may contribute to gliadin-induced epithelial damage but could also have potential protective effects during treatment. Arginine (Arg), through its metabolism via the inducible nitric oxide synthase (iNOS) and arginase pathways, contributes to immune regulation. This review underscores the therapeutic potential of AAs as adjunctive targets to gluten-free diets (GFD), offering avenues for nutritional interventions, enzyme therapies, and biomarker development. A deeper understanding of AA-mediated mechanisms may pave the way for personalized management strategies to improve clinical outcomes in CD.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03490-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562417","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}