Amino Acids[JOURNAL]
Sun
200 papers
Tryptophan metabolites clearance in hemodialyzed patients.
Zakrocka I, Mlak R, Moniczewska N … +6 more , Boczkowska S, Kloc R, Kocki T, Urbańska EM, Załuska W, Kronbichler A
Amino Acids · 2026 Feb · PMID 41653312 · Full text
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 kid...
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.
Unveiling the anti-glycation properties of acetylsalicylic acid: targeted inhibition of albumin glycation.
Tupe R, Durge A, Jagdale A
Amino Acids · 2026 Feb · PMID 41649596 · Full text
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-gl...
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.
Epithelial hypusination regulates Helicobacter pylori-induced gastric inflammation.
Gobert AP, McNamara KM, Hawkins CV … +10 more , Asim M, Barry DP, Delgado AG, Rose KL, Patel P, Tyree RN, Carson KS, Coburn LA, Piazuelo MB, Wilson KT
Amino Acids · 2026 Feb · PMID 41627564 · Full text
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...
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 Helicobacter pylori. Immunohistochemical analyses revealed increased expression of DHPS and hypusinated EIF5A (EIF5A) in the gastric mucosa of patients with H. pylori 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 (Dhps) and confirmed the reduction of DHPS and EIF5A in GECs. H. pylori-infected Dhps mice exhibited an attenuation of gastric histologic inflammation scores compared with infected Dhps controls, without alteration in bacterial colonization levels. Quantitative proteomics of isolated GECs showed that Dhps deletion altered the expression of proteins involved in organismal injury, cancer, and gastrointestinal diseases in naïve mice. Upon H. pylori infection, inflammatory and immune response proteins, including signaling factors and immunoglobulin mediators, were less induced in Dhps GECs, and pathways linked to tissue injury and inflammation were selectively downregulated. Together, these findings demonstrate that epithelial hypusination supports H. pylori-driven gastric inflammation without affecting bacterial persistence. Targeting DHPS-dependent EIF5A hypusination may thus represent a novel therapeutic strategy to limit H. pylori-associated mucosal injury and disease progression.
Quantitative analysis of amino acid excretion and consumption by Methanothermobacter marburgensis in fed-batch cultivation mode.
Reischl B, Schupp B, Fink C … +1 more , Rittmann SKR
Amino Acids · 2026 Feb · PMID 41627526 · Full text
The methanogenic archaeon Methanothermobacter marburgensis offers a promising alternative to traditional bacterial systems for the sustainable production of proteinogenic amino acids (AAs), eliminating the need for sugar...
The methanogenic archaeon Methanothermobacter marburgensis 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) concentrations and gas compositions. M. marburgensis demonstrated excretion of a wide spectrum of AAs with distinct profiles shaped by nitrogen availability. While high NH concentrations suppressed total AA excretion, NH 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, M. marburgensis 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.
Genetic commonalities between rare subtypes of ALS and CMT: insights into molecular mechanisms of neurodegeneration.
Aynaashe A, Kursula P
Amino Acids · 2026 Feb · PMID 41621017 · Full text
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 compl...
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 (DYNC1H1, KIF5A, SPG11, DCTN1), protein homeostasis (NEFH, VCP, SOD1), RNA metabolism (GARS, SETX), cellular stress response (HSPB1, FIG4), and mitochondrial function (MFN2, CHCHD10). 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.
Polyamine metabolism as a regulator of cellular and organismal aging.
Uemura T, Takayama J, Oguro A … +1 more , Terui Y
Amino Acids · 2026 Jan · PMID 41617890 · Full text
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 ph...
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.
Analysis of amino acids in Mucuna pruriens supplements using hydrophilic interaction liquid chromatography-tandem mass spectrometry.
Phillips CR, Violi JP, Bishop DP … +1 more , Rodgers KJ
Amino Acids · 2026 Jan · PMID 41575577 · Full text
Mucuna pruriens (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)....
Mucuna pruriens (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.
NGS and the design of an optimized phage display workflow for peptide discovery.
Bakhshinejad B, Kjaer A
Amino Acids · 2025 Dec · PMID 41452380 · Full text
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 n...
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.
MTR4 methylation-dependent degradation activates mTORC1 signaling to promote glioma cell survival under methionine starvation.
Wang L, Lou Q, Chang J … +6 more , Xu Z, Yang F, Tu Q, Zhang J, Xu W, Tong M
Amino Acids · 2025 Dec · PMID 41428109 · Full text
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...
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.
Evaluation of the clinical characteristics and potentially prognostic factors in HER2-positive breast cancer.
Shi L, Xi PW, Li Z … +3 more , Wu J, Zhang X, Zhang L
Amino Acids · 2025 Dec · PMID 41398532 · Full text
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...
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. 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.
Evaluation of the antimicrobial-cytotoxic activities and molecular docking study of L-cysteine ethyl ester and L-cysteine methyl ester.
Karaca TD, Balcı H, Aysan A … +2 more , Sert Y, Doğan A
Amino Acids · 2025 Nov · PMID 41276728 · Full text
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 or...
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 Staphylococcus aureus and Gram-negative Escherichia coli 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.
Impacts of conditionally essential amino acids, cysteine, and tyrosine on intestinal inflammation in celiac disease.
Mahmoudi Ghehsareh M, Bakhtiari S, Asri N … +4 more , Rezaei-Tavirani M, Jahani-Sherafat S, Masotti A, Rostami-Nejad M
Amino Acids · 2025 Nov · PMID 41269353 · Full text
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 A...
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.
Aromatic amino acid-metal ion interactions: comparative effects of alkali and Zn on acidity and coordination behavior via QM studies.
Kalhor S, Fattahi A
Amino Acids · 2025 Nov · PMID 41264125 · Full text
Among the 20 standard amino acids, aromatic amino acids hold particular importance due to their crucial roles in protein-protein interactions. These residues, including phenylalanine, tyrosine, tryptophan, and histidine,...
Among the 20 standard amino acids, aromatic amino acids hold particular importance due to their crucial roles in protein-protein interactions. These residues, including phenylalanine, tyrosine, tryptophan, and histidine, contribute significantly to protein structure and function through their ability to engage in non-covalent interactions, such as π-π stacking and cation-π interactions. In addition, the acid-base duality of aromatic amino acids makes their interactions with metal ions particularly valuable. These interactions are implicated in several essential biological processes, including protein biosynthesis, enzyme catalysis, and molecular recognition. While the interactions between transition metal ions and amino acids have been extensively studied and well-documented, the role of alkali metal ions in similar contexts has received comparatively less attention. However, their influence on amino acid coordination and stability cannot be overlooked, especially given their biological relevance in processes such as ionic regulation, enzyme activation, and membrane transport. The results of this study demonstrate that the complexation of aromatic amino acids with alkali metal ions enhances their acidity. Additionally, we examined the detailed interactions of these metals with the aromatic amino acids.
Novel octapeptide containing the RGD sequence as a potential anti-SARS-CoV-2 agent: design, synthesis, and theoretical studies.
Lemos R, Ortiz O, Almagro L … +4 more , Makowski K, Rodríguez H, Albericio F, Suárez M
Amino Acids · 2025 Nov · PMID 41264082 · Full text
The design of peptide-based inhibitors targeting cell receptors represents a promising strategy in the development of antiviral agents. In this study, a novel octapeptide containing the RGD sequence was rationally design...
The design of peptide-based inhibitors targeting cell receptors represents a promising strategy in the development of antiviral agents. In this study, a novel octapeptide containing the RGD sequence was rationally designed to explore its potential interaction with integrins. The peptide was functionalized with a malonic moiety to enhance its binding capabilities and potential bioactivity. Conformational and physicochemical properties were evaluated using DFT-PBEh-3c calculations. Molecular docking studies revealed favorable interactions with the integrin αβ, including coordination with the Mg²⁺ ion at the active site. The peptide was successfully synthesized via Fmoc-based solid-phase peptide synthesis (SPPS) and fully characterized by NMR, IR, MS, and RP-HPLC.
Decoding incretin resistance: a mechanistic framework to reclassify therapeutic variability for GLP-1 receptor agonist therapy.
Fajkić A, Lam YW, Belančić A
Amino Acids · 2025 Nov · PMID 41236578 · Full text
This article introduces a mechanistic framework to reclassify suboptimal responses to GLP-1 receptor agonists. It defines three mechanistic subtypes of incretin resistance-receptor-level, post-receptor, and secretory-hig...
This article introduces a mechanistic framework to reclassify suboptimal responses to GLP-1 receptor agonists. It defines three mechanistic subtypes of incretin resistance-receptor-level, post-receptor, and secretory-highlighting their distinct pathways and therapeutic implications. This model promotes personalized care by moving beyond the oversimplified 'non-responder' classification.
Essential amino acid supplementation for pressure ulcers: pathophysiological rationale and results from a pilot study.
Świątkiewicz M, Lejczak A, Foltyński P … +1 more , Grieb P
Amino Acids · 2025 Nov · PMID 41236568 · Full text
Pressure ulcers (PU) are a major and serious problem affecting millions of people. Malnutrition, frequently co-occurring with PU, is considered modifiable risk factor, and dietary supplements currently recommended for su...
Pressure ulcers (PU) are a major and serious problem affecting millions of people. Malnutrition, frequently co-occurring with PU, is considered modifiable risk factor, and dietary supplements currently recommended for supporting PU healing contain a high amount of protein and some additives (zinc, vitamin C, arginine). Unfortunately, many patients with PU suffer from chronic kidney disease and would not tolerate a high-protein diet. Amino acid profiling of the blood serum of PU patients has shown decreased concentrations of exogenous amino acids histidine, tryptophan and threonine. Their common feature is a low daily requirement, 4 to 15 mg/kg body weight. In animal experiments, various types of stress increase metabolic demand for these amino acids. On the other hand, stress significantly slows down wound healing, both in animals and in humans. Considering these observations, a pilot clinical trial in the quasi-experimental design has been performed to assess the effect of Pellicar-F, a proprietary food composition containing histidine in the form of carnosine, plus tryptophan and threonine on PU control. After six weeks patients receiving daily doses of the aforementioned food composition, compared to control patients, displayed statistically significant reduction of the pressure ulcer area. Further evaluation of this product in pressure ulcers and other chronic wounds is indicated.
Intelligent design and synthesis of nucleobase and amino acid-based ligands to inhibit the JAK2 enzyme to treat rheumatoid arthritis.
Zarei A, Fatahi A
Amino Acids · 2025 Nov · PMID 41198951 · Full text
Rheumatoid arthritis is the most prevalent form of autoimmune arthritis. In modern drug development, computer-aided drug design plays a crucial role not only in discovering new therapeutic compounds but also in assessing...
Rheumatoid arthritis is the most prevalent form of autoimmune arthritis. In modern drug development, computer-aided drug design plays a crucial role not only in discovering new therapeutic compounds but also in assessing their potential efficacy. This study employs ligand-based pharmacophore modeling to identify novel drug candidates without requiring an initial target protein structure. Essential chemical features were extracted from nucleotides, amino acids, and sulfonylaziridine derivatives to construct potential drug scaffolds. Ligands exhibiting similar structural characteristics were then screened for promising chemical interactions. Using MATLAB software, the initial pool of 4,000 candidates was narrowed down to 330, which was further reduced to 58 and finally to 8 through AutoDock screening. These top candidates were further analyzed using molecular docking (static analysis) and molecular dynamics simulations (dynamic analysis). Among them, the compound CPROSCP demonstrated favorable dynamic stability, an appropriate hydrodynamic radius, minimal distortion of protein structure, and advantageous binding energy. The synthesized drug candidate achieved a yield of approximately 92%, with IR and NMR spectroscopy confirming its successful synthesis and high purity.
Plant amino acid analogues as antimicrobial agents.
Demash D, Stasyk O, Stasyk O
Amino Acids · 2025 Oct · PMID 41123709 · Full text
Plants are known as a source of different biologically active compounds, which are uncommon for other kingdoms of life. Among them are different amino acid analogues, which are synthesized and accumulated in certain plan...
Plants are known as a source of different biologically active compounds, which are uncommon for other kingdoms of life. Among them are different amino acid analogues, which are synthesized and accumulated in certain plants as a passive defense mechanism against herbivorous insects and grazing mammals. As a rule, cell protein synthesis machinery of herbivores cannot effectively differentiate between standard proteinogenic amino acids and their specific plant analogues, resulting in misincorporation of the latter into nascent proteins and their malfunctioning, which constitutes a mechanism of plant defense. Examples of such amino acids are analogues of arginine (canavanine, indospicine), proline (azetidine-2-carboxylic acid), and cysteine/lysine (thialyasine). This review summarizes existing knowledge on these and other related amino acids as potential antibacterial and antifungal agents, including their possible targets and known resistance mechanisms. We also discuss the possibility of using amino acid analogues as sole antimicrobial agents or in combination with known antibacterials and antifungals. We also propose a strategy of enhancing the antimicrobial activity of amino acid analogue by concomitant starvation for the corresponding standard amino acid, which has been proven efficient in anticancer studies. Such an approach might potentially help to overcome, at least partially, microbial resistance to known antibiotics, especially when such resistance relies on increased protein synthesis in pathogen cells.
Myocardial protection by acidic amino acids and natural dipeptides: potential for an underused resource.
King N
Amino Acids · 2025 Oct · PMID 41123699 · Full text
Stopping then restarting the blood flow to the heart can cause ischaemia reperfusion (IR) injury. This can happen during revascularisation following a myocardial infarction and during on pump cardiac surgery using cardio...
Stopping then restarting the blood flow to the heart can cause ischaemia reperfusion (IR) injury. This can happen during revascularisation following a myocardial infarction and during on pump cardiac surgery using cardioplegic arrest. Despite extensive studies to identify cardioprotective interventions, the myocardium continues to sustain significant injury. Therefore, there is a need to identify agents that can be used during IR. This review focuses on the potential cardioprotective role for acidic amino acids and natural dipeptides using evidence from experimental studies and clinical trials with particular emphasis on their membrane transport. Acidic amino acids are present at high concentration in the heart with a large tissue to plasma concentration gradient, where they are involved in protein synthesis and intermediary metabolism. During cardiac insults they are lost from heart cells but replenishment leads to cardioprotection through energy provision, protection against the production of reactive oxygen species production and improved calcium homeostasis. One important determinant of the intracellular concentration of acidic amino acids and natural dipeptides is membrane transport. The expression and activity of the acidic amino acids transporters EAAT1-3 and the dipeptide transporter, PEPT2 have been demonstrated in membrane vesicles and isolated cardiomyocytes. Improvements in our understanding of these different transport mechanisms should lead to the maximisation of acidic amino acid and natural dipeptide uptake during IR leading to improved cardioprotection.
Lysine malonylation as a therapeutic target: implications for metabolic, inflammatory, and oncological disorders.
Unar A
Amino Acids · 2025 Oct · PMID 41107644 · Full text
Lysine malonylation (Kmal) is an emerging posttranslational modification (PTM) intricately linked to cellular metabolism and disease pathogenesis. This review explores the regulatory mechanisms of Kmal, emphasizing the r...
Lysine malonylation (Kmal) is an emerging posttranslational modification (PTM) intricately linked to cellular metabolism and disease pathogenesis. This review explores the regulatory mechanisms of Kmal, emphasizing the role of malonyl-CoA as its donor substrate and Sirtuin 5 (SIRT5) as its primary demalonylase. Kmal significantly influences metabolic homeostasis, inflammation, and cancer by modifying key enzymes involved in glycolysis, fatty acid oxidation, and mitochondrial function. In metabolic disorders such as type 2 diabetes and obesity, aberrant malonylation contributes to insulin resistance, lipid accumulation, and oxidative stress. Inflammatory conditions, including sepsis and autoimmune diseases, involve malonylation-driven regulation of immune responses, particularly through GAPDH-mediated cytokine translation. Furthermore, in oncogenesis, malonylation plays a dual role: it suppresses tumor growth by impairing metabolic flux while also being exploited by cancer cells to maintain proliferation. Therapeutic interventions targeting Kmal include SIRT5 modulators, malonyl-CoA metabolism regulators, and small-molecule inhibitors that modulate lysine acylation dynamics. Advances in mass spectrometry and proteomics have expanded our understanding of the biological functions of Kmal; however, its full physiological and pathological significance remains under investigation. Future research should focus on elucidating tissue-specific malonylation patterns and their interactions with other PTMs to refine therapeutic strategies. By integrating metabolic regulation with disease mechanisms, Kmal has emerged as a crucial biochemical modification with broad implications for metabolic, inflammatory, and oncological disorders. Understanding its regulatory network will be pivotal in developing precision medicine approaches aimed at mitigating disease progression and restoring cellular homeostasis.
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