Amino Acids[JOURNAL]
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200 papers
Maternal dietary citrulline supplementation increases fetal growth and programs pancreatic development in the lambs.
Herring AB, Herron KS, Lemcke LG … +2 more , Johnson GA, Satterfield MC
Amino Acids · 2026 Apr · PMID 41989601 · Full text
Intrauterine growth restriction (IUGR), caused by maternal undernutrition, impairs fetal growth and increases the risk for postnatal metabolic dysfunction. L-arginine can mitigate these effects; however, its use in sheep...
Intrauterine growth restriction (IUGR), caused by maternal undernutrition, impairs fetal growth and increases the risk for postnatal metabolic dysfunction. L-arginine can mitigate these effects; however, its use in sheep is limited by ruminal microbial degradation. Interestingly, L-citrulline, the precursor for arginine synthesis, bypasses ruminal catabolism and may be a practical alternative. This study evaluated if maternal L-citrulline supplementation to nutrient restricted ewes from gestational days (GD) 28 to 140 (term = 147) enhances fetal growth in lambs. Gestating ewes were fed 50% of National Research Council (NRC) nutritional recommendations to induce IUGR and received either L-citrulline (0.40% of diet) or an isonitrogenous alanine control (0.61% of diet). Birth weight and pre-suckling blood samples were collected, and lambs remained with dams until postnatal day 60 (PND60) (citrulline: n = 13; alanine: n = 10). Lambs from L-citrulline treated ewes were heavier at birth (P = 0.05) and PND60 (P < 0.05), with greater (P < 0.05) absolute weights of the pancreas, brain, liver, and small intestine. Pancreatic mass per gram of body weight was greater (P < 0.05) in citrulline lambs. The relative proportion of endocrine and exocrine pancreas were not different between treatments. Circulating insulin concentrations were greater (P = 0.05) at birth and circulating glucose concentrations were increased (P < 0.05) in the citrulline lambs on PND60. These results suggest that maternal L-citrulline supplementation is a viable alternative to arginine for improving fetal growth during maternal malnutrition, with benefits persisting through weaning.
Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.
Fang J, Ling J, Liu X … +5 more , Wang Y, Huang Y, Cao Z, Zou Y, Xiong H
Amino Acids · 2026 Apr · PMID 41979669 · Full text
Nitrogen metabolism plays a key role in maintaining normal physiological functions of the organism and cell proliferation and differentiation. Nitrogen metabolism in normal human body maintains a dynamic balance to meet...
Nitrogen metabolism plays a key role in maintaining normal physiological functions of the organism and cell proliferation and differentiation. Nitrogen metabolism in normal human body maintains a dynamic balance to meet the body's demand for synthesis of biological macromolecules such as proteins and nucleic acids. However, in the process of tumor development, the nitrogen metabolism of tumor cells is reprogrammed to meet the demand of rapid proliferation, showing significantly different metabolic characteristics from normal cells. Key enzymes in the tumor microenvironment affect nitrogen metabolism through multiple mechanisms, providing essential nitrogen sources and energy for tumor cells. In-depth exploration of the regulatory mechanisms of tumor nitrogen metabolism not only helps to reveal the molecular basis of tumor development, but also provides a theoretical basis for the development of new tumor therapeutic strategies. In this paper, the relationship between nitrogen metabolism and tumors is systematically elaborated from the characteristics of nitrogen metabolism in normal people, the reprogramming of nitrogen metabolism in tumor patients, the influence of key enzymes on nitrogen metabolism in the tumor microenvironment, as well as the mechanism of tumor nitrogen metabolism regulation, etc., so as to provide references for the related research.
Spider peptides from Brachypelma smithi with slightly different amino acids at their C-terminal loops exert different insecticidal activities.
Clement H, Corrales-García L, Carpanta V … +4 more , Jaimes G, Montero-Domínguez PA, Diego-García E, Corzo G
Amino Acids · 2026 Apr · PMID 41957118 · Publisher ↗
The insecticidal molecules of spiders persistently evolve to ensure rapid paralysis of their prey, and the best molecules are transmitted to their progeny. Here, we cloned two insecticidal peptides, Bs2 and Bs3, from the...
The insecticidal molecules of spiders persistently evolve to ensure rapid paralysis of their prey, and the best molecules are transmitted to their progeny. Here, we cloned two insecticidal peptides, Bs2 and Bs3, from the venom glands of the theraphosid Brachypelma smithi. Bs2 and Bs3 are 90.2% identical, but they exhibit interesting structural differences at their C-termini, including a connecting disulfide bond (residues Cys15-Cys36 for Bs2 and Cys15-Cys30 for Bs3). The genomic origin of Bs2 and Bs3 may be a cause for gene duplication events. Moreover, Bs2 differs in two residues from Tal1 (95.1% identical), an insecticidal peptide, from the tarantula Tliltocatl albopilosus. Likewise, Bs3 is similar to Asp3a from Aphonopelma sp., a peptide that targets mammalian Cav (voltage-dependent Ca2 + channel), but it has not been tested in insects. Bs2 and Bs3 were cloned and recombinantly expressed in bacterial cells, and their paralytic effects were tested on three species of insects. The insecticidal peptide rBs2 with the connecting loop Cys15-Cys36 was significantly more insecticidal than that of rBs3 when affecting Galleria mellonella larvae (Lepidoptera). Yet, the insecticidal peptide rBs3 with the connecting loop Cys15-Cys30 was significantly more insecticidal than that of rBs2 when affecting Acheta domesticus nymph crickets (Orthoptera), and Gromphadorhina portentosa cockroaches (Blattodea). rBs2 and rBs3 structural models show a low-structured C-terminal in rBs3, which correlates with a more flexible amino acid sequence of such C-terminal from residues Tyr30 to Leu42. Since insecticidal spider peptides are constantly evolving for prey capture, they are valuable ion channel antagonists for understanding insect cell receptors, and they are also promising leads for insect control.
The remarkable legacy of the K6/ODC mouse: mechanisms of polyamine-promoted tumorigenesis revealed.
Gilmour SK
Amino Acids · 2026 Apr · PMID 41925768 · Full text
Using the well-studied two-stage model of skin carcinogenesis, the first transgenic mouse with targeted expression of a polyamine metabolic enzyme was generated 30 years ago. Ornithine decarboxylase (ODC), a key regulati...
Using the well-studied two-stage model of skin carcinogenesis, the first transgenic mouse with targeted expression of a polyamine metabolic enzyme was generated 30 years ago. Ornithine decarboxylase (ODC), a key regulating enzyme of polyamine biosynthesis, was constitutively expressed in the outer root sheath cells of hair follicles near the bulge stem cell niche using a keratin 6 promoter in K6/ODC mice. Early studies using K6/ODC mice demonstrated that polyamines play an essential role in the early promotional phase of skin tumorigenesis. Treatment with inhibitors of ODC activity blocked the formation of skin tumors and caused the rapid regression of existing tumors. We review how use of the K6/ODC mouse has shown that elevated polyamines in epithelial cells stimulate proliferation and invasiveness, recruit stem cells, alter chromatin remodeling and cell signaling leading to metabolic reprogramming, increase vascularization, activate underlying fibroblasts, and have powerful effects on immune cell function, all contributing to the development and progression of tumors.
At the core of global bioenergy: polyamines and transglutaminases in chloroplasts.
Serafini-Fracassini D, Del Duca S
Amino Acids · 2026 Mar · PMID 41874791 · Full text
Chloroplasts are the energy factories of photosynthetic life. The energy and the plant biomass of the planet depend on the activity of chloroplasts. Their efficiency results from a delicate balance between membrane organ...
Chloroplasts are the energy factories of photosynthetic life. The energy and the plant biomass of the planet depend on the activity of chloroplasts. Their efficiency results from a delicate balance between membrane organization, metabolic regulation and the maintenance of protein homeostasis. Among the molecular factors that support chloroplast structure and function, polyamines (PAs) and transglutaminases (TGases) have emerged as key regulators of photosynthetic performance and stress tolerance. PAs stabilize thylakoid membranes, influence proton-motive force partitioning, modulate chlorophyll biosynthesis and protect the photosynthetic apparatus from oxidative damage, thereby contributing to increased photoprotection and delayed senescence. TGases, particularly the plastid-localized isoforms, catalyze the covalent conjugation of PAs to stromal and thylakoid proteins, including RuBisCo and light-harvesting complexes (LHC). These reactions affect protein stability, supramolecular assembly, and the dynamic remodeling of LHC. Light-, pH- and redox-dependent activation of TGases links PA dependent protein modification to the regulation of photosynthetic efficiency and stress responses. This review integrates biochemical, structural and physiological evidence to highlight how PAs and TGases operate at the interface of light-to-chemical energy conversion. Both are involved in membrane organisation and maintaining protein quality. Understanding this molecular network provides new perspectives for improving plant performance, enhancing tolerance to abiotic stress and sustaining biomass production, notably that of agriculture interest, under changing environmental conditions.
The role of N-acetylcysteine and glutathione in the management of Parkinson's disease: a systematic review of oxidative biomarkers and clinical outcomes.
Mohammed I, Nankya Y, Hong UT … +3 more , Kan A, Abdelhafid AM, Latunde-Dada GO
Amino Acids · 2026 Mar · PMID 41874704 · Full text
Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterised by the loss of dopaminergic neurons, leading to both motor and non-motor symptoms. Oxidative stress is a significant contributor to the p...
Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterised by the loss of dopaminergic neurons, leading to both motor and non-motor symptoms. Oxidative stress is a significant contributor to the pathophysiology of PD, and glutathione (GSH) depletion contributes to neuronal damage. N-acetylcysteine (NAC), a bioavailable cysteine donor, can support endogenous GSH synthesis and may also exert antioxidant effects independent of GSH replenishment. NAC and GSH are proposed neuroprotective interventions due to their antioxidant properties. This systematic review evaluated the effects of NAC and GSH on oxidative stress and PD symptoms, comparing them with healthy controls or a placebo. A systematic search was conducted in Cochrane Library, PubMed, Web of Science, Ovid (Embase and MEDLINE), Scopus, and ProQuest for studies published between January 2003 and December 2024, including randomised controlled trials (RCTs) and non-randomised studies. Two reviewers assessed the study quality and extracted data. The primary outcome was the change in motor and non-motor symptoms as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) and were interpreted using minimal clinically important difference (MCID) thresholds. Secondary outcomes included biochemical redox markers such as blood GSH, cerebrospinal fluid (CSF) GSH, GSSG, and GSH/GSSG ratio and imaging-based functional outcomes, particularly DAT binding assessed by DaTscan SPECT. The GSH/GSSG ratio reflects redox status (reduced vs. oxidised glutathione), CSF outcomes primarily reported NAC concentrations, and brain GSH was quantified using magnetic resonance spectroscopy (MRS). Exclusion criteria included studies on conditions other than PD, those that did not use NAC or GSH as the primary intervention, and those without a comparator group. Nine studies, conducted between 2009 and 2019, met the inclusion criteria and involved 196 participants. NAC improved both motor and non-motor symptoms and significantly increased GSH/GSSG ratios, GSH levels in the CSF, and DAT binding. In contrast, intranasal GSH showed only modest increases in brain levels without significant improvements in symptoms or oxidative stress markers. The studies had limitations, including small sample sizes, short intervention durations, and inconsistencies in dosage and administration routes. These factors constrain the strength of the conclusions, and evidence for both NAC and GSH remains preliminary. Furthermore, while NAC shows promise as a neuroprotective intervention, findings for GSH are inconclusive. More large-scale, long-term randomised controlled trials are needed to validate these results and explore NAC and GSH's long-term therapeutic potential in managing PD.
Adaptive crosstalk between polyamine metabolism, translation, and autophagy sustains energy homeostasis in mammals during starvation: a scoping review.
Karimi K, Roberts SC, Carter NS … +2 more , Hofer SJ, Karimi R
Amino Acids · 2026 Mar · PMID 41874700 · Full text
Mammalian cells tightly regulate the shift between catabolism and anabolism to maintain energy homeostasis during starvation. Among other adaptations, cells adapt to nutrient restriction by downregulating translation, th...
Mammalian cells tightly regulate the shift between catabolism and anabolism to maintain energy homeostasis during starvation. Among other adaptations, cells adapt to nutrient restriction by downregulating translation, the most energy consuming cellular process, and inducing autophagy. Polyamines are ubiquitous small polycationic endogenous metabolites indispensable for cellular growth and viability. They regulate both autophagy and translation processes, coordinating an intriguing metabolic hub during cellular adaptation to starvation. Recent studies have highlighted a complex role for polyamines during starvation and a growing body of evidence underscores various nutrients and nutrient-sensing pathways that modulate autophagy through their influence on the mammalian target of rapamycin complex 1 (mTORC1) signaling. mTORC1 is a master regulator of cellular anabolism, including translation. Less explored is how these coordinated systems adapt and respond to starvation. This scoping review explores how changes in polyamine metabolism and related molecules orchestrate the adaptive crosstalk between autophagy, mTORC1, and translation to ensure that the mammalian cell conserves energy to maintain essential cellular functions during starvation. Our review highlights that spermidine and one of its major cellular targets, translation initiation factor 5A (eIF5A), facilitate translation of transcription factor EB (TFEB) to induce autophagy during starvation. Starvation suppresses mTORC1 activity, leading to reduced ribosome biogenesis and translation while promoting autophagy to meet cellular energy demands. We discuss the adaptive mechanisms by which reduced levels of acetyl-CoA, amino acids, EP300, glucose, insulin, and S-adenosylmethionine inhibit mTORC1 and simultaneously induce autophagy. Additionally, we describe the adaptive role that glucagon, Sestrin2, and urea play to inhibit mTORC1 and how eIF5A, glucagon, spermidine, and TFEB induce autophagy.
Taurine supplementation and systemic lupus erythematosus in preclinical studies: a systematic review of clinical outcomes and underlying mechanisms.
Malek Mahdavi A, Javadivala Z, Orooji N
Amino Acids · 2026 Mar · PMID 41874670 · Full text
Taurine (Tau) is a sulfur-containing amino acid that has therapeutic roles in several diseases, including inflammatory conditions. The involvement of Tau in modulating systemic lupus erythematosus (SLE) autoimmunity has...
Taurine (Tau) is a sulfur-containing amino acid that has therapeutic roles in several diseases, including inflammatory conditions. The involvement of Tau in modulating systemic lupus erythematosus (SLE) autoimmunity has been indicated in preclinical models, but reports are contradictory. This systematic review aimed to summarize current research regarding the potential role of Tau in SLE, to notice knowledge gaps, and to offer suggestions for the way ahead. The literature search was carried out using PubMed, Scopus, Web of Science, and Google Scholar databases until October 2025. Search alert services were also applied to notice related papers published after the primary search. All studies investigating the effects of Tau in SLE that met the inclusion criteria were eligible. Out of 77 articles initially found, only six preclinical studies (animal and in-vitro) were eligible, and no qualified clinical study was identified. Five studies indicated that Tau was helpful in improving clinical parameters, decreasing T helper 1 (Th1) and Th17 cells and inflammatory mediators (e.g., tumor necrosis factor-α, C-reactive protein, and inducible nitric oxide synthase), removing reactive oxygen species and decreasing oxidative markers like malondialdehyde, increasing regulatory T (Treg) and Th2 cells and anti-inflammatory interleukin-4 and interleukin-10 cytokines, increasing antioxidant enzymes superoxide dismutase and glutathione peroxidase, and inhibiting both FAS- and mitochondrial-dependent apoptotic signaling components. However, only one preclinical study reported that Tau aggravated SLE progression characterized by increased generation of type I interferons, enhanced autoantibodies and proteinuria, further lymphocyte activation, and critical nephritis. The current review provides evidence about the role of Tau in SLE and highlights the importance of further well-designed clinical trials to confirm these results, establish optimal dose and assess safety and long-term efficacy.
Dysregulation of SIRT1, polyamines and miRNA editing in cancer and aging.
Ramamonjiharisoa MBM, Liu S
Amino Acids · 2026 Mar · PMID 41863647 · Full text
Interest in RNA editing has emerged in molecular medicine due to its widespread dysregulation and therapeutic potential. Its regulatory mechanisms in governing non-coding RNAs, especially microRNAs (miRNAs) remain largel...
Interest in RNA editing has emerged in molecular medicine due to its widespread dysregulation and therapeutic potential. Its regulatory mechanisms in governing non-coding RNAs, especially microRNAs (miRNAs) remain largely unresolved. Emerging evidence in diseases reveals a functional convergence between miRNAs and polyamine metabolism, two systems traditionally studied separately. miRNAs serve as primary substrates for adenosine deaminase acting on RNA (ADAR) which could regulate polyamine metabolism via the sirtuin (SIRT1)-p53 axis, forming a disease-relevant loop. Indeed, in many proliferative malignancies, hyper-editing of miRNAs coincides with high polyamine levels and promotes SIRT1-mediated p53 deacetylation. Conversely, in many age-related diseases, hypo-editing and polyamine loss blunt this pathway. This review dissects this emerging ADAR-editing-miRNA-polyamine circuit anchored on the SIRT1-p53 axis. We propose this as a unifying working model to integrate disparate correlative observations, providing a roadmap for future validation studies to confirm its potential for combinatorial therapeutic targets and diagnostic biomarkers.
Arginine improves growth and health status of post-larval Litopenaeus vannamei by modulating amino acid metabolism and enhancing antioxidative defense.
Chen X, Xie H, Pan Y … +6 more , Qu K, Liu Y, Song J, Tan B, Yang Q, Xie S
Amino Acids · 2026 Mar · PMID 41826560 · Full text
This study investigated the dietary arginine requirement for post-larval Litopenaeus vannamei based on growth performance and hepatopancreatic health indicators. A 25-day feeding trial was conducted. Five iso-nitrogenous...
This study investigated the dietary arginine requirement for post-larval Litopenaeus vannamei based on growth performance and hepatopancreatic health indicators. A 25-day feeding trial was conducted. Five iso-nitrogenous and iso-lipidic diets contained graded arginine levels (2.12-2.85%, A0-A4). Increasing dietary arginine significantly promoted growth performance without affecting whole‑body composition, while the highest survival rate occurred in shrimp fed the 2.85% diet. Antioxidant responses were endpoint-dependent: SOD and GPX reached their highest activities at A2-A3 (with A2 showing marked activation), whereas T-AOC and CAT continued to increase and MDA decreased at higher arginine levels. Quadratic regression of SOD activity estimated an optimum at approximately 2.51%. Expression of arginine metabolism genes (agm, nos) and antioxidant genes (gpx, sod) was significantly upregulated in A2, whereas protein synthesis‑related genes were strongly activated in A4. Metabolomic profiling identified 141 differential metabolites, with L‑hydroxyarginine and DL‑proline upregulated and creatine downregulated in A4. In parallel, γ‑aminobutyric acid (GABA) and S‑adenosylmethionine (SAM) contents increased, indicating modulation of neurotransmission and methylation. Enrichment analysis showed significant effects on arginine and proline metabolism, glycerophospholipid metabolism, and GABAergic pathways. Correlation and network analyses suggested that elevated arginine improves growth and antioxidative capacity by reinforcing amino acid, phospholipid, and energy metabolism and supporting neuromodulation. In conclusion, integrating regression-estimated optima for antioxidant-related indices with growth and survival outcomes within the tested range suggests that the recommended dietary arginine requirement for post-larval Litopenaeus vannamei is approximately 2.51-2.85%, which promotes growth and survival, supports hepatopancreatic health, enhances antioxidant capacity, and modulates amino acid and lipid metabolism.
Association between plasma concentrations of galectin 3, growth differentiation factor 15, soluble suppression of tumourigenicity 2, and cystatin C and clinical parameters and survival in patients with end-stage renal disease undergoing haemodialysis.
Ptak M, Cader-Ptak A, Marcinowska Z … +6 more , Dziedziejko V, Safranow K, Kwiatkowska E, Ciechanowski K, Pawlik A, Domański L
Amino Acids · 2026 Mar · PMID 41824076 · Full text
The treatment of chronic kidney disease is based mainly on haemodialysis. During this procedure, cardiovascular haemodynamic parameters change, which can lead to complications in the circulatory system and shorten patien...
The treatment of chronic kidney disease is based mainly on haemodialysis. During this procedure, cardiovascular haemodynamic parameters change, which can lead to complications in the circulatory system and shorten patient survival. Currently, new biomarkers are being sought that could predict survival in haemodialysis patients. The aim of this study was to evaluate whether Gal-3, GDF-15, sST2, and CysC could be useful biomarkers in patients with end-stage renal failure undergoing haemodialysis in predicting the patient survival. This study included 76 patients with end-stage kidney disease treated with haemodialysis. We assessed the variability in the plasma concentrations of these proteins; evaluated correlations between Gal-3, GDF-15, and sST2 concentrations and selected haemodialysis parameters; and determined the relationship between the risk of death and Gal-3, GDF-15, sST2, and CysC concentrations. There was a decrease in the Gal-3 plasma concentrations and an increase in the GDF-15 and sST2 plasma concentrations during haemodialysis. Among the studied proteins, only the sST2 concentrations differed significantly between the patients who survived and died. The logarithm of the sST2 concentrations, both before and after haemodialysis, was an independent mortality risk factor in univariate analysis (respectively: hazard ratio [HR] 3.179, 95% confidence interval [CI] 1.492-6.777, p = 0.0027, and HR 3.011, 95% CI 1.447-6.264, p = 0.0032) and multivariate analysis, which also included age, male gender, and body mass index (respectively: HR 2.776, 95% CI 1.306-5.903, p = 0.0080, and HR 2.496, 95% CI 1.224-5.090, p = 0.012). These results suggest the use of sST2 in clinical practice to identify patients at higher risk of death.
Plasma branched-chain amino acids in chronic kidney disease: associations with atherogenic lipids and mortality.
Suliman ME, Qureshi AR, Troise D … +5 more , Zhang Q, Bárány P, Heimbürger O, Stenvinkel P, Lindholm B
Amino Acids · 2026 Mar · PMID 41795728 · Full text
Branched-chain amino acids (BCAAs) are essential nutrients that promote muscle protein anabolism but also associate with cardiometabolic diseases; however, their role in chronic kidney disease (CKD) remains unclear. We i...
Branched-chain amino acids (BCAAs) are essential nutrients that promote muscle protein anabolism but also associate with cardiometabolic diseases; however, their role in chronic kidney disease (CKD) remains unclear. We investigated plasma BCAA levels and their associations with metabolic parameters and survival in CKD patients. Plasma BCAA levels, along with clinical and laboratory parameters, were measured in 328 patients with CKD stage 5 (median age 54 years, 60% males). BCAA concentrations in 83 community-dwelling controls (median age 51 years, 66% males) served as comparators. Multivariate linear regression analysis was employed to identify predictors of BCAA levels. Competing risk regression analysis was conducted to assess 5-year risk of all-cause and cardiovascular mortality in relation to total and individual BCAAs (valine, isoleucine, and leucine). Plasma BCAA levels were lower compared to controls (P < 0.0001) and positively associated with triglycerides and the atherogenic index of plasma, while inversely associated with high density lipoprotein-cholesterol (HDL-C), Apo-A, and Lp (a). After adjustments for confounders, low vs. high tertile of total BCAAs associated with increased risk of cardiovascular mortality (sub-hazard ratio [sHR] 2.37, 95% confidence interval [CI], 1.08-5.21) and low tertile of valine associated with higher risk of both all-cause mortality (sHR 2.05, 95% CI 1.10-3.79) and cardiovascular mortality (sHR 2.46, 95% CI 1.15-5.26). In CKD, higher levels of BCAAs associated with an atherogenic lipid profile while lower BCAAs levels associated with increased cardiovascular mortality risk, and low valine was associated with higher both all-cause and cardiovascular mortality risk. Monitoring and potentially modulating BCAA levels could have prognostic or therapeutic implications in advanced CKD.
Targeting amino acid metabolic pathways: a novel therapeutic strategy for hyperuricemia-associated complications.
Zhang X, Wang W, Yang L … +6 more , Sun Y, Sun H, Zhao X, Sun H, Yan G, Wang X
Amino Acids · 2026 Mar · PMID 41793522 · Full text
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...
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.
Amino acid metabolism-related model for prognosis and immunity in gastric cancer.
Zhang H, Ye W, Zeng L … +2 more , Wang L, Gui L
Amino Acids · 2026 Mar · PMID 41784817 · Full text
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...
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.
Branched-chain polyamines: evolutionary adaptation and biotechnological potential.
Fujiwara S, Fukuda W
Amino Acids · 2026 Mar · PMID 41784802 · Full text
Branched-chain polyamines (BCPAs), exemplified by N⁴-bis(aminopropyl)spermidine, are distinctive polycations that occur predominantly in thermophilic bacteria and euryarchaeal archaea. Their dedicated aminopropyltransfer...
Branched-chain polyamines (BCPAs), exemplified by N⁴-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 S-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 Thermococcus kodakarensis 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.
Tryptophan metabolism reprogramming regulates Th1/Th2 immune balance and inhibits mast cell activation.
Huang D, Huang D, Su L … +7 more , He C, Zhang X, Peng J, Fan L, Cao Y, Chen L, Tong H
Amino Acids · 2026 Feb · PMID 41764151 · Full text
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...
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.
Probiotic and microbial modulation of polyamine production: an emerging avenue for neuroprotection in neurodegenerative disorders.
Adhikari T, Saha P
Amino Acids · 2026 Feb · PMID 41721117 · Full text
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 neuroinflam...
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.
Association of homoarginine with arginine and disease severity in COVID-19 patients: comment.
Daungsupawong H, Wiwanitkit V
Amino Acids · 2026 Feb · PMID 41686330 · Full text
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Using animal models to decipher the role of polyamines in the pancreas and β Cell.
Puente AA, Kinderlerer L, Castillo LJ … +2 more , Mirmira RG, Tersey SA
Amino Acids · 2026 Feb · PMID 41677974 · Full text
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 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.
Solid-state cultivation-specific agmatine production by Aspergillus oryzae: current understanding and perspectives.
Akasaka N, Watanabe D, Yasukawa K … +1 more , Fujiwara S
Amino Acids · 2026 Feb · PMID 41655144 · Full text
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...
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 Aspergillus oryzae, 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 (Ao-ADC1) responsible for this unique agmatine production. This mini-review summarizes current knowledge on solid-state cultivation-specific agmatine production by A. oryzae, with a particular focus on the discovery and biochemical characteristics of Ao-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 A. oryzae 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.
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