Amino Acids[JOURNAL]
Sun
200 papers
Dietary exposure to creatine-precursor amino acids in the general population.
Nedeljkovic D, Ostojic SM
Amino Acids · 2025 May · PMID 40413365 · Full text
BACKGROUND: Creatine is a semi-essential nutrient that plays a critical role in energy metabolism, with dietary intake and endogenous synthesis contributing to overall creatine availability. While dietary creatine intake...
BACKGROUND: Creatine is a semi-essential nutrient that plays a critical role in energy metabolism, with dietary intake and endogenous synthesis contributing to overall creatine availability. While dietary creatine intake has been studied extensively, limited data exist on the dietary exposure to its precursor amino acids-glycine, arginine, and methionine-and their contribution to endogenous creatine synthesis. This study aimed to assess the dietary intake of these precursors in U.S. children and adults using data from the Third National Health and Nutrition Examination Survey (NHANES III) and to compare endogenous creatine synthesis with direct dietary creatine intake. METHODS: We analyzed NHANES III dietary recall data from 29,945 individuals aged 2 years and older. Intakes of glycine, arginine, methionine, and creatine were calculated per kilogram of body weight. The contribution of precursor amino acids to endogenous creatine synthesis was estimated using established metabolic conversion factors. RESULTS: The mean daily intakes of glycine, arginine, methionine, and creatine were 59.6 ± 0.4 mg/kg, 77.2 ± 0.5 mg/kg, 31.9 ± 0.2 mg/kg, and 15.5 ± 0.1 mg/kg, respectively. Estimated endogenous creatine synthesis from precursor amino acids was significantly greater than dietary creatine intake across all age groups (P < 0.01), with precursor-derived creatine production averaging 41.9 ± 0.3 mg/kg body weight per day, approximately 2.7 times higher than dietary creatine intake. Creatine precursor availability declined with age, with the lowest values observed in individuals aged ≥ 65 years. CONCLUSION: This study provides the first comprehensive evaluation of total creatine availability in a representative U.S. population, highlighting the predominance of endogenous synthesis over direct dietary intake. These findings suggest that creatine metabolism is largely dependent on precursor amino acid intake and that certain populations, particularly older adults, may be at higher risk for reduced creatine availability. Future research should explore the physiological implications of these findings and potential dietary interventions to optimize creatine status across the lifespan.
Cationic antimicrobial peptide CC34 potential anticancer and apoptotic induction on cancer cells.
Dong L, Li Y, Zhang Y … +1 more , Su S
Amino Acids · 2025 May · PMID 40413361 · Full text
To evaluate the potential of antimicrobial peptide CC34 for use as therapeutic agents for gastric cancer SGC-7901 and hepatocellular carcinoma HepG-2. In this study, the antibacterial activity and antibacterial mechanism...
To evaluate the potential of antimicrobial peptide CC34 for use as therapeutic agents for gastric cancer SGC-7901 and hepatocellular carcinoma HepG-2. In this study, the antibacterial activity and antibacterial mechanism were tested by the minimum inhibitory concentration (MIC) analysis, minimal bactericidal concentration (MBC) analysis, bacterial biofilm and NaCl permeability assays. Then, we assessed the hemolytic activity and cytotoxicity of CC34 for red blood cells and cancer cells, respectively. Apoptosis assay, cell cycle analysis, determination of intracellular ROS, western blot analysis caspase activity assay and ATP assay were further performed to investigate the mechanism of CC34 affected cancer cells. The novel peptide could inhibit Gram-negative and Gram-positive bacteria, with low hemolytic activity against mouse and chicken erythrocytes. Moreover, CC34 exhibited higher inhibitory activity against biofilm formation. In addition, our data showed that CC34 significantly suppressed cell proliferation, in a dose dependent manner. CC34 induced apoptosis, induced reactive oxygen species (ROS) generation, inhibited B-cell lymphoma-2 (Bcl-2) expression, increase B-cell lymphoma protein 2 associated X protein (Bax) expression, release of cytochrome c (Cyt C), promoted caspase-3 and - 9 activities and reduced cellular ATP levels in cancer cells. Our results indicate that CC34 with antimicrobial activity have a highly potent ability to induced apoptosis via mitochondrial-mediated apoptotic pathway in cancer cells.
Targeting LAT1 with JPH203 to reduce TNBC proliferation and reshape suppressive immune microenvironment by blocking essential amino acid uptake.
Zhao Y, Pu C, Liu K … +1 more , Liu Z
Amino Acids · 2025 May · PMID 40379991 · Full text
The competitive uptake of essential amino acids (EAAs) by breast cancer cells is associated with poor patient prognosis and the development of an immunosuppressive tumor microenvironment. L-type amino acid transporters,...
The competitive uptake of essential amino acids (EAAs) by breast cancer cells is associated with poor patient prognosis and the development of an immunosuppressive tumor microenvironment. L-type amino acid transporters, LAT1 (SLC7 A5) and LAT2 (SLC7 A8) are major mediators of EAAs transmembrane uptake and are overexpressed in some tumor tissues. However, the distribution and functional roles of these transporters across breast cancer subtypes have not been fully elucidated. This study aims to investigate the therapeutic potential of targeting EAA transporters, particularly LAT1, in triple-negative breast cancer (TNBC) and its role in remodeling the tumor immune microenvironment. The distribution of EAA transporters across breast cancer subtypes was analyzed using multi-omics data. The effects of LAT1 targeting on TNBC cell proliferation and EAA uptake were evaluated using SLC7 A5 knockout and LAT1 inhibitors in vitro experiments. A 4T1-BALB/c tumor-bearing mouse model with normal immune function was constructed to investigate the effects of LAT1 targeting on tumor growth and immune microenvironment remodeling in vivo. TNBC demonstrated a strong dependence on LAT1-mediated EAAs uptake. Targeting LAT1 limited the exogenous supply of EAAs, leading to amino acid starvation, cell cycle arrest, and increased apoptosis in TNBC cells. The in vivo experiments, using a 4T1-BALB/c tumor-bearing mouse model, showed that LAT1 targeting inhibited tumor growth and remodeled the immunosuppressive tumor microenvironment. Targeting LAT1 improved PD-L1-associated immune suppression and improved the efficacy of PD-1 antibody treatment, producing synergistic anti-tumor effects. This study highlights the therapeutic potential of targeting LAT1 in TNBC, particularly in remodeling the tumor immune microenvironment. The findings provide a promising strategy for immune combination therapy in TNBC.
Effect of histidine and carnosine on haemoglobin recovery in anaemia induced-kidney damage and iron-loading mouse models.
Vera-Aviles M, Moreno-Fernandez J, Kose T … +2 more , Hider R, Latunde-Dada GO
Amino Acids · 2025 May · PMID 40355605 · Full text
Histidine and carnosine can form complexes with divalent metal ions such as Fe, potentially providing stability to intracellular labile iron. Anaemia is a common comorbidity in the late stages of kidney disease, and pati...
Histidine and carnosine can form complexes with divalent metal ions such as Fe, potentially providing stability to intracellular labile iron. Anaemia is a common comorbidity in the late stages of kidney disease, and patients are treated with erythropoiesis-stimulating agents (ESAs) and iron supplementation. However, iron supplementation is also associated with worse long-term outcomes. The purpose of this study is to investigate how histidine and carnosine supplementation can reduce symptoms of anaemia of chronic kidney disease (CKD) and the effects associated with iron-overloaded conditions. Adenine-induced chronic kidney disease mice were treated with histidine and carnosine by oral gavage for 10 days. Additionally, a model involving iron overload in mice was established, and these mice received concurrent treatment with histidine and carnosine. Haemoglobin, non-haem iron, malondialdehyde (MDA) and iron parameters were measured. Carnosine increased erythropoietin (EPO) levels (35.62 µg/ml ± 11.43) and resulted in haemoglobin repletion (16.7 g/dL ± 3.4). When iron was supplemented alongside with histidine or carnosine, there were better effects on haemoglobin repletion (14.22 ± 1.7 and 13.82 ± 2.15 g/ dL respectively), ferritin (59.5 ± 16.4, 52 ± 29.5 µg/ml) and non-haem iron (0.8 ± 0.21, 0.7 ± 0.38 nmol/mg), than the group receiving iron alone (p < 0.05). Furthermore, histidine and carnosine reduced non-haem iron and MDA, in iron-loaded conditions (p < 0.05). These positive effects observed in histidine and carnosine could be associated with reactive oxygen species (ROS) scavenging. EPO restoring levels in CKD model and the increment in haemoglobin and ferritin in carnosine treatments suggested the potential formation of a ternary complex with iron-glutathione. In conclusion, our results indicate the beneficial effect of histidine and carnosine in the context of iron supplementation for the correction of haemoglobin and protection against iron-loaded conditions.
Therapeutic peptides: chemical strategies fortify peptides for enhanced disease treatment efficacy.
Li Q, Chao W, Qiu L
Amino Acids · 2025 May · PMID 40338379 · Full text
Therapeutic peptides, as a unique form of medication composed of orderly arranged sequences of amino acids, are valued for their high affinity, specificity, low immunogenicity, and economical production costs. Currently,...
Therapeutic peptides, as a unique form of medication composed of orderly arranged sequences of amino acids, are valued for their high affinity, specificity, low immunogenicity, and economical production costs. Currently, more than 100 peptides have already secured market approval. Over 150 are actively undergoing clinical trials, while an additional 400-600 are in the preclinical research stage. Despite this, their clinical application is limited by factors such as salt sensitivity, brief residence in the bloodstream, inadequate cellular uptake, and high structural flexibility. By employing suitable chemical methods to modify peptides, it is possible to regulate important physicochemical factors such as charge, hydrophobicity, conformation, amphiphilicity, and sequence that affect the physicochemical properties and biological activity of peptides. This can overcome the inherent deficiencies of peptides, enhance their pharmacokinetic properties and biological activity, and promote continuous progress in the field of research. A diverse array of modified peptides is currently being developed and investigated across numerous therapeutic fields. Drawing on the latest research, this review encapsulates the essential physicochemical factors and significant chemical modification strategies that influence the properties and biological activity of peptides as pharmaceuticals. It also assesses how physicochemical factors affect the application of peptide drugs in disease treatment and the effectiveness of chemical strategies in disease therapy. Concurrently, this review discusses the prospective advancements in therapeutic peptide development, with the goal of offering guidance for designing and optimizing therapeutic peptides and to delve deeper into the therapeutic potential of peptides for disease intervention.
Association of homoarginine with arginine and disease severity in COVID-19 patients.
Zhao Z, Wei TT, Zhang WX … +11 more , Zhang SS, Wu R, Li F, Yang H, Zhang Q, Xi J, Zhou Y, Wang T, Du J, Lu QB, Ge Q
Amino Acids · 2025 May · PMID 40332615 · Full text
This study explored the relationship between the concentrations of homoarginine and arginine and between homoarginine concentration and laboratory parameters in coronavirus disease 2019 (COVID-19) patients with different...
This study explored the relationship between the concentrations of homoarginine and arginine and between homoarginine concentration and laboratory parameters in coronavirus disease 2019 (COVID-19) patients with different severity to demonstrate the role of homoarginine in the progress of COVID-19. The laboratory-confirmed COVID-19 patients were included from Peking University Third Hospital during December 2022 to January 2023. Serum, urine, and stool samples were collected from the patients and detected by liquid chromatography-mass spectrometry. Totally 46 patients were recruited, including 18 in the mild group, 19 in the severe group, and 9 fatal. The concentration of homoarginine was positively correlated with the concentration of arginine in serum (r = 0.50), urine (r = 0.55), and stool samples (r = 0.39), respectively (all P < 0.001). The serum concentration and urine concentration of homoarginine were lower in severe patients than in mild patients (both P < 0.05). 13 indicators reflecting immunity and coagulation, including but not limited to T cell, white blood cell, natural killer cell, interleukin 6 (IL-6), and IL-8, had statistically significant correlations with both disease severity and the homoarginine concentration. Patients with hypertension were significantly associated with the decreased serum homoarginine (odds ratio 10.905, 95% confidence interval 1.454 - 137.144). Our results suggest that the homoarginine plays a role in the progress of COVID-19, which may be achieved by influencing arginine metabolism.
Safety assessment of L-ornithine oral intake in healthy subjects: a systematic review.
Yang H, Kuramochi Y, Sato S … +2 more , Sakai R, Hayamizu K
Amino Acids · 2025 May · PMID 40323503 · Full text
L-Ornithine (L-Orn) is a nonessential amino acid but has many physiological roles. Accordingly, L-Orn has been used as a functional food or dietary supplement to ameliorate various maladies, but there is only limited inf...
L-Ornithine (L-Orn) is a nonessential amino acid but has many physiological roles. Accordingly, L-Orn has been used as a functional food or dietary supplement to ameliorate various maladies, but there is only limited information available about its safety. The safety of a chemical compound is generally assessed via non-clinical and clinical studies, but safety information derived from human studies is particularly important. Recently, systematic reviews have been used to assess the safety as well as the effectiveness and usefulness of such studies. Therefore, we conducted an assessment of the safety of L-Orn by systematically reviewing clinical studies. Specifically, we performed a comprehensive search of databases for clinical trials in which L-Orn was added to ordinary diets (i.e., orally administered) in healthy individuals. Focusing on PubMed, Cochrane Library, Ichushi-Web, and EBSCOhost, we comprehensively searched for reports on human studies on the oral ingestion of L-Orn. We identified 22 articles as subjects for this SR. Among these articles, the maximum L-Orn dose was 14,025 mg/person/day in the form of L-Orn hydrochloride and the maximum duration of administration was 156 days. The main observed adverse events were gastrointestinal disorders. Indexing these adverse events, the no observed adverse effect level was estimated to be 12,000 mg/person/day for L-Orn in the form of L-Orn hydrochloride. When we conducted an integration analysis on the risk of adverse events, the difference between those with and without L-Orn supplementation in the risk of gastrointestinal disorders was 0.00 (95% confidence interval: ±0.02, P = 1.00), so no significant effects were observed. (UMIN000033371).
Metabolomic analysis reveals key changes in amino acid metabolism in colorectal cancer patients.
Ramzy A, Abdelmoneim TK, Arafat M … +6 more , Mokhtar M, Bakkar A, Mokhtar A, Anwar W, Magdeldin S, Enany S
Amino Acids · 2025 May · PMID 40314699 · Full text
The number of colorectal cancer (CRC) patients is steadily growing worldwide, particularly in developing nations. Nonetheless, recent advances in early detection studies and therapy alternatives have reduced CRC mortalit...
The number of colorectal cancer (CRC) patients is steadily growing worldwide, particularly in developing nations. Nonetheless, recent advances in early detection studies and therapy alternatives have reduced CRC mortality in affluent countries, despite rising incidence. Gut microbiota and their metabolites may contribute to tumor growth and reduced therapeutic efficacy. This preliminary study sought to uncover metabolic fingerprints in colorectal cancer patients. It also emphasizes the correlation between the gut microbiome, microbial metabolism, and altered metabolites in CRC. In this study, stool samples from 20 CRC patients and matched healthy controls were enrolled. Untargeted metabolomics approach based on an ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-MS/MS) were applied. Statistical approaches, pathway enrichment analysis, and network analysis were employed to unleash CRC perturbed metabolic pathways and putative biomarkers. The study identified a distinct manually curated metabolite profile that is substantially linked to CRC. The steroidogenesis, aspartate, tryptophan (Trp), and urea cycle were the most significant pathways that concurrently contributed to CRC.Prominently, among other pathways, Trp metabolism was identified as a critical pathway, indicating a possible connection between the development of CRC and gut microbiota. In a nutshell the notable resulted metabolites reveal auspicious biomarkers for the initial diagnosis as well as surveilling of CRC progression. This preliminary study highlights the potential involvement that gut bacteria may contribute in CRC patients. Further investigation into the composition of the gut microbiome associated with this metabolic profile may lead to the identification of novel biomarkers for early detection and possible targets for treatment.
Integrative analysis of taurine metabolism-related genes prognostic signature with immunotherapy and identification of ABCB1 and GORASP1 as key genes in nasopharyngeal carcinoma.
Feng Z, Yang Y, Luo W … +12 more , Li J, Xie Z, Zuo L, Duan M, Zuo D, Mo R, Tang X, Yi S, He X, Liu F, Ma N, He F
Amino Acids · 2025 Apr · PMID 40272558 · Full text
Taurine is an amino acid with several physiological functions and has been shown to be involved in the anti-tumor of human nasopharyngeal carcinoma (NPC) cells. However, the role of taurine metabolism-related genes (TMRG...
Taurine is an amino acid with several physiological functions and has been shown to be involved in the anti-tumor of human nasopharyngeal carcinoma (NPC) cells. However, the role of taurine metabolism-related genes (TMRGs) in NPC has not been reported. We integrated data from the Genecards, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Expression Omnibus(GEO) databases to identify differentially expressed genes associated with taurine metabolism in NPC patients. Gene Ontology (GO) and KEGG analyses were conducted to investigate the underlying mechanisms. Subsequently, Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct a taurine metabolism-related prognostic signature. Survival, medication sensitivity, and immunological microenvironment evaluations were performed to assess the prognostic utility of the model. Finally, immunohistochemistry (IHC) experiments were performed to validate the model's prognostic reliability. In addition, we further verified the reliability of our research results through molecular docking and single-cell sequencing. Our prognostic model was based on three pivotal TMRGs (ABCB1, GORASP1, and EZH2). Functional analysis revealed a strong association between TMRGs and miRNAs in cancer. Notably, increased risk scores correlated with worsening tumor malignancy and prognosis. Significant disparities in immune microenvironment, immune checkpoints, and drug sensitivity were observed between the high- and low-risk groups. The protein expression patterns of the selected genes in clinical NPC samples were validated using immunohistochemistry. Molecular docking verified the interaction between these three core genes and taurine, which was further supported by single-cell sequencing showing significant expression variation among different cell clusters in NPC. We had elucidated the functions, therapeutic potential, and prognostic significance of three key genes related to taurine metabolism in NPC through multidimensional research and experimental validation. This research provided valuable insights and potential avenues for improved NPC management.
Retraction Note: Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats.
Liu C, Yang CX, Chen XR … +6 more , Liu BX, Li Y, Wang XZ, Sun W, Li P, Kong XQ
Amino Acids · 2025 Mar · PMID 40133687 · Full text
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Silencing of RNFT2 suppresses cell proliferation and migration through mTORC1 signaling pathway in gastric cancer.
Wang Y, Ma Q, Zhu Z … +3 more , Sang H, Fan H, Li Z
Amino Acids · 2025 Mar · PMID 40097779 · Full text
Excellent biomarkers for predicting survival or therapeutic targets are still lacking in gastric cancer (GC), which is one of the most common causes of cancer-related death worldwide. Ring finger protein, transmembrane 2...
Excellent biomarkers for predicting survival or therapeutic targets are still lacking in gastric cancer (GC), which is one of the most common causes of cancer-related death worldwide. Ring finger protein, transmembrane 2 (RNFT2), which has been reported to be involved in proteolytic process, but how it functions in tumors is rarely investigated. In the present study, we explored the biological property of RNFT2 in GC, we found that RNFT2 was significantly upregulated in GC, and could serve as a tumor marker to predict prognosis. A series of in vitro cell function experiments were performed, we found that knockdown of RNFT2 expression in GC cells could inhibit cell invasion, migration and proliferation. Besides, in vivo experiments also showed that silencing RNFT2 expression in gastric cancer cells significantly reduced tumor size. Furthermore, through gene set enrichment analysis (GSEA) and immunoblotting studies, we observed that RNFT2 might influence the proliferation, invasion and migration of GC cells through the mTORC1 signaling pathway. In summary, our results clarified the carcinogenic role of RNFT2 in GC progression, provided inspiration to further understand the molecular mechanism of GC and made RNFT2 as a potential target for GC diagnosis and therapy.
Unveiling the tissue-specific landscape of nuclear-encoded mitochondrial genes involved in amino acid metabolism in buffalo.
Sadeesh EM, Lahamge MS
Amino Acids · 2025 Feb · PMID 40019559 · Full text
Mitochondria play a pivotal role in energy production, metabolism, and cellular signaling, serving as key regulators of cellular functions, including differentiation and tissue-specific adaptation. The interplay between...
Mitochondria play a pivotal role in energy production, metabolism, and cellular signaling, serving as key regulators of cellular functions, including differentiation and tissue-specific adaptation. The interplay between mitochondria and the nucleus is crucial for coordinating these processes, particularly through the supply of metabolites for epigenetic modifications that facilitate nuclear-mitochondrial interactions. To investigate tissue-specific mitochondrial adaptations at the molecular level, we conducted RNA sequencing data analyses of kidney, heart, brain, and ovary tissues of female buffaloes, focusing on variations in mitochondrial gene expression related to amino acid metabolism. Our analysis identified 82 nuclear-encoded mitochondrial transcripts involved in amino acid metabolism, with significant differential expression patterns across all tissues. Notably, the heart, brain, and kidney-tissues with higher energy demands-exhibited elevated expression levels compared to the ovary. The kidney displayed unique gene expression patterns, characterized by up-regulation of genes involved in glyoxylate metabolism and amino acid catabolism. In contrast, comparative analysis of the heart and kidney versus the brain revealed shared up-regulation of genes associated with fatty acid oxidation. Gene ontology and KEGG pathway analyses confirmed the enrichment of genes in pathways related to amino acid degradation and metabolism. These findings highlight the tissue-specific regulation of mitochondrial gene expression linked to amino acid metabolism, reflecting mitochondrial adaptations to the distinct metabolic and energy requirements of different tissues in buffalo. Importantly, our results underscore the relevance of mitochondrial adaptations not only for livestock health but also for understanding metabolic disorders in humans. By elucidating the molecular mechanisms of mitochondrial function and their tissue-specific variations, this study provides insights that could inform breeding strategies for enhanced livestock productivity and contribute to therapeutic approaches for human metabolic diseases. Thus, our findings illustrate how mitochondria are specialized in a tissue-specific manner to optimize amino acid utilization and maintain cellular homeostasis, with implications for both animal welfare and human health.
Serum amino acid alterations in hyperuricemia: potential targets for renal disease prevention.
Sheng Q, Ma Y, Geng B … +9 more , Chen J, Cheng J, Liu S, Li R, Li X, Wang J, Lu H, Gao F, Gao F
Amino Acids · 2025 Feb · PMID 39966264 · Full text
UNLABELLED: Observational studies have linked uric acid (UA) levels and kidney disease to amino acid homeostasis, but the causal relationship is unclear. This study aims to determine if elevated UA affects amino acid lev...
UNLABELLED: Observational studies have linked uric acid (UA) levels and kidney disease to amino acid homeostasis, but the causal relationship is unclear. This study aims to determine if elevated UA affects amino acid levels and whether amino acids mediate this relationship, focusing on the causal links between UA, circulating amino acids, and kidney disease. METHODS: This study utilized Uox-KO mice as a hyperuricemia model, assessed renal injury through blood biochemistry and pathology, analyzed serum amino acid changes via targeted amino acidomics, and employed Mendelian randomization to investigate the causal links between uric acid, amino acids, and renal disease. RESULTS: Hyperuricemia Uox-KO mice have significantly higher serum UA and renal impairment markers, with histopathological analysis showing extensive renal tissue damage. Changes in amino acid balance were found in the mice's serum, with key metabolites like alanine, isoleucine, leucine, aspartic acid, cysteine, glutamate, and glycine potentially influencing UA pathophysiology. Genetically predicted UA was positively correlated with chronic renal failure (CRF) and blood urea nitrogen(BUN) levels and negatively with serum cystatin C (eGFRcys) and serum creatinine (eGFRcrea). Alanine (Ala) mediated the effect of UA on elevated CRF and BUN risk, accounting for 4.5% of the UA-CRF relationship and 14.4% of the UA-BUN association. CONCLUSION: In hyperuricemia mice, serum amino acids undergo metabolic changes. Genetically predicted UA levels are positively linked to CRF and BUN, but negatively linked to eGFRcys and eGFRcrea. Ala mediates UA's effect on CRF and BUN risk, indicating Ala could be a target for preventing renal diseases caused by hyperuricemia.
L-tyrosine inhibits the formation of amyloid fibers of human lysozyme at physiological pH and temperature.
López S, Rojo-Domínguez A, López-Simeon R … +2 more , Sosa-Peinado A, Nájera H
Amino Acids · 2025 Feb · PMID 39955695 · Full text
Amyloid fibers are implicated in numerous diseases, making their study crucial for identifying effective therapeutic compounds. This research highlights the ability of L-tyrosine to inhibit the formation of amyloid fiber...
Amyloid fibers are implicated in numerous diseases, making their study crucial for identifying effective therapeutic compounds. This research highlights the ability of L-tyrosine to inhibit the formation of amyloid fibers in human lysozyme. At a 1:1 molar ratio under physiological conditions (pH 7.4, 37 °C), L-tyrosine significantly reduces amyloid fiber formation, as evidenced by a decrease in thioflavin T fluorescence. Differential scanning calorimetry (DSC) shows a major energy requirement for temperature denaturation when the lysozyme is in the presence of L-tyrosine. Additionally, chemical denaturation experiments reveal a shift in the intrinsic fluorescence spectrum of lysozyme in the presence of L-tyrosine, indicating a direct interaction. Computational docking studies with Molecular Operating Environment (MOE) further confirm that L-tyrosine binds effectively, exhibiting similar binding energies to those of the natural substrate. This study underscores L-tyrosine's potential as a strong inhibitor of amyloid fiber formation, demonstrating its stabilizing effect on lysozyme and its promise in therapeutic applications.
Metabolism of arginine in juvenile largemouth bass (Micropterus salmoides) after oral or intraperitoneal administration of arginine or its substrates.
Wang J, Zhang J, Li X … +7 more , Xu HY, Yang Y, Zhang J, Feng W, Chen Q, Dong F, Han T
Amino Acids · 2025 Feb · PMID 39945913 · Full text
The main objective of this experiment was to study the metabolism of arginine in juvenile largemouth bass (Micropterus salmoides). A total of 300 healthy fish (average weight of 25 ± 0.5 g) were randomly assigned to ten...
The main objective of this experiment was to study the metabolism of arginine in juvenile largemouth bass (Micropterus salmoides). A total of 300 healthy fish (average weight of 25 ± 0.5 g) were randomly assigned to ten groups. Experimental fish were orally administered or intraperitoneally injected with 0.9% sodium chloride, arginine, arginine-aspartate, citrulline, and glutamate solutions, respectively. They were euthanized at 10, 30, 60, 120, and 240 min after oral administration or intraperitoneal injection, and various tissue samples were subsequently collected for analysis. The results revealed that serum ornithine and citrulline concentrations of largemouth bass were significantly increased by oral administration of arginine or arginine-aspartate (P < 0.05). Intraperitoneal injection of arginine or arginine-aspartate solution significantly elevated the concentrations of ornithine and citrulline in the serum, liver, kidney, and muscles (P < 0.05). The concentrations of citrulline, ornithine, and arginine in serum and muscle increased significantly at 4 h after intraperitoneal injection of glutamate (P < 0.05). Intraperitoneal injection of citrulline significantly increased the concentrations of ornithine and arginine in the serum and muscles (P < 0.05). The research findings demonstrate that both free and small peptide forms of arginine were rapidly degraded to ornithine due to the high arginase activity in various tissues of largemouth bass. Additionally, the pathway of synthesizing citrulline from glutamate and then arginine from citrulline may exist in largemouth bass, but the exact location of this synthesis process may differ from that found in mammals.
Amino acid stable carbon isotopes in nail keratin illuminate breastfeeding and weaning practices of mother - infant dyads.
Salahuddin H, Waters-Rist AL, Longstaffe FJ
Amino Acids · 2025 Jan · PMID 39883182 · Full text
Compound-specific stable carbon isotope analysis of amino acids (CSIA-AA) is widely used in ecological studies to analyze food-webs and is gaining use in archaeology for investigating past diets. However, its use in reco...
Compound-specific stable carbon isotope analysis of amino acids (CSIA-AA) is widely used in ecological studies to analyze food-webs and is gaining use in archaeology for investigating past diets. However, its use in reconstructing breastfeeding and weaning practices is not fully understood. This study evaluates the efficacy of stable carbon isotope analysis of amino acids in early life diet reconstruction by analyzing keratin from fingernail samples of three mother-infant pairs during late gestation and early postpartum periods. Our results show that stable carbon isotope ratios (δC) of glycine, and to a lesser extent glutamate, effectively trace the onset of exclusive breastfeeding and the end of weaning in infants. We propose that glycine's 'conditionally essential' metabolic pathway during infancy allows it to reflect maternal glycine δC, indicating breastmilk consumption. Subtle changes in glutamate δC likely result from its 'non-essential' status. Additionally, δC values of glycine and glutamate indicate maternal physiological and pathological stress due to catabolic effects such as gluconeogenesis. These findings have significant implications for ecological and archaeological research using CSIA-AA for dietary reconstructions. They highlight the need to understand how metabolic pathways affecting δC of amino acids may change over an individual's lifespan or be altered due to various forms of stress.
Targeted delivery of curcumin and CM11 peptide against hepatocellular carcinoma cells based on binding affinity of PreS1-coated chitosan nanoparticles to SB3 protein.
Rahmani D, Taheri RA, Moosazadeh Moghaddam M
Amino Acids · 2025 Jan · PMID 39862295 · Full text
In recent years, the use of cationic peptides as alternative drugs with anticancer activity has received attention. In this study, the targeted release of curcumin (Cur) and CM11 peptide alone and together against hepato...
In recent years, the use of cationic peptides as alternative drugs with anticancer activity has received attention. In this study, the targeted release of curcumin (Cur) and CM11 peptide alone and together against hepatocellular carcinoma (HCC) was evaluated using chitosan nanoparticles (CS NPs) coated with Pres1 that target the SB3 antigen of HCC cells (PreS1-Cur-CM11-CS NPs). SB3 protein is the specific antigen of HCC and the PreS1 peptide is a part of the hepatitis B antigen, which can specifically bind to the SB3 protein. Chitosan was used to prepare NPs. To Cur and CM11 loading, drugs were added to the CS solution in appropriate concentrations. Pres1 was coupled to the surface of the NPs using EDC catalyst to target NPs against HepG2 cells. SEM and DLS analysis confirmed that the PreS1-Cur-CM11-CS NPs had a size of about 132 nm, the ideal size for penetrating the cell membrane. The loading of Cur and CM11 was equal to 87% and 65%, respectively, which had a sustained and better release in the acidic environment than in the physiological environment. The MTT assay showed that PreS1-Cur-CM11-CS NPs act in a targeted and specific manner with the highest toxicity on the HepG2 cells compared to the control by a decrease in viability of about 26% after 48 h based on cell apoptosis. The results showed that PreS1-Cur-CM11-CS NPs are capable of targeted and specific drug release against HepG2 cancer cells and have significant potential to fight this cancer.
Quantum chemical study of molecular properties of small branched-chain amino acids in water.
Boča R, Rádiková Ž, Štofko J … +2 more , Vranovičová B, Rajnák C
Amino Acids · 2025 Jan · PMID 39827427 · Full text
Four aliphatic amino acids-α-aminobutyric acid (AABA), β-aminobutyric acid (BABA), α-aminoisobutyric acid (AAIBA) and β-aminoisobutyric acid (BAIBA) were investigated in water as a solvent by two quantum chemical methods...
Four aliphatic amino acids-α-aminobutyric acid (AABA), β-aminobutyric acid (BABA), α-aminoisobutyric acid (AAIBA) and β-aminoisobutyric acid (BAIBA) were investigated in water as a solvent by two quantum chemical methods. B3LYP hybrid version of DFT was used for geometry optimization and a full vibrational analysis of neutral molecules, their cations and anions in the canonical and zwitterionic forms (6 forms for each species). Ab initio DLPNO-CCSD(T) method was applied in the geometry pre-optimized by B3LYP. Calculated molecular descriptors involve dipole moment, quadrupole moment, dipole polarizability, energy of zero-point vibration and total entropic term which enter the standard Gibbs energy. In addition, a set of collective electronic and thermodynamic properties associated with redox process were evaluated: ionization energy, electron affinity, chemical hardness, molecular electronegativity, electrophilicity index, absolute oxidation and reduction potentials. A mutual comparison of these structural isomers including γ-aminobutyric acid (GABA) shows high degree of similarity in molecular descriptors. However, cluster analysis of 12 electro neutral, linear and branched amino acids with 2 - 6 carbon atoms discriminates them into five clusters. It is found that the electrophilicity index correlates with the absolute reduction potential along a straight line (24 items). The reduction potential for canonical structure varies between 1.21 V (glycine) and 1.45 V (AABA) whereas for the zwitterionic form it is visibly lower 0.52-1.11 V. The highest absolute reduction potential > 1.43 V is shown by α-amino acids: α-alanine, AABA (homoalanine) and AAIBA having 2-methyl or 2-ethyl functional group. The calculated absolute oxidation potential correlates with the adiabatic ionization energy and can be used as a criterion of the antioxidant capacity. According to thermodynamic data, the SPLET mechanism of the electron-proton coupled transfer is favored over the alternative SET-PT mechanism. This work contributes to the creation of a database of molecular properties of amino acids based on the same method and basis set.
Alterations of amino acids in older adults with Alzheimer's Disease and Vascular Dementia.
Ma X, Wang XM, Tang GZ … +9 more , Wang Y, Liu XC, Wang SD, Peng P, Qi XH, Qin XY, Wang YJ, Wang CW, Zhou JN
Amino Acids · 2025 Jan · PMID 39825947 · Full text
Metabolomics provide a promising tool for understanding dementia pathogenesis and identifying novel biomarkers. This study aimed to identify amino acid biomarkers for Alzheimer's Disease (AD) and Vascular Dementia (VD)....
Metabolomics provide a promising tool for understanding dementia pathogenesis and identifying novel biomarkers. This study aimed to identify amino acid biomarkers for Alzheimer's Disease (AD) and Vascular Dementia (VD). By amino acid metabolomics, the concentrations of amino acids were determined in the serum of AD and VD patients as well as age-matched healthy controls. Several differences in the concentration of amino acids were observed in AD patients compared to both healthy controls and VD patients. However, no significant distinction was found between healthy controls and VD patients. Considering comorbidities, cystine levels were higher in AD than in VD among non-diabetic patients, but not in those with diabetes. Notably, creatine, spermidine, cystine, and tyrosine demonstrated favorable results in decision curve analyses and good discriminative performances, suggesting their potential for clinical application. These fundings give novel perspectives of serum amino acids for predicting metabolic pathways in AD and VD pathogenesis.
Systematic qualitative proteome-wide analysis of lysine malonylation profiling in Platycodon grandiflorus.
Yang Q, Xu S, Jiang W … +7 more , Meng F, Wang S, Sun Z, Chen N, Peng D, Liu J, Xing S
Amino Acids · 2025 Jan · PMID 39812870 · Full text
In recent years, it was found that lysine malonylation modification can affect biological metabolism and play an important role in plant life activities. Platycodon grandiflorus, an economic crop and medicinal plant, had...
In recent years, it was found that lysine malonylation modification can affect biological metabolism and play an important role in plant life activities. Platycodon grandiflorus, an economic crop and medicinal plant, had no reports on malonylation in the related literature. This study qualitatively introduces lysine malonylation in P. grandiflorus. A total of 888 lysine malonylation-modified proteins in P. grandiflorus were identified, with a total of 1755 modification sites. According to the functional annotation, malonylated proteins were closely related to catalysis, binding, and other reactions. Subcellular localization showed that related proteins were enriched in chloroplasts, cytoplasm, and nuclei, indicating that this modification could regulate various metabolic processes. Motif analysis showed the enrichment of Alanine (A), Cysteine (C), Glycine (G), and Valine (V) amino acids surrounding malonylated lysine residues. Metabolic pathway and protein-protein interaction network analyses suggested these modifications are mainly involved in plant photosynthesis. Moreover, malonylated proteins are also involved in stress and defense responses. This study shows that lysine malonylation can affect a variety of biological processes and metabolic pathways, and the contents are reported for the first time in P. grandiflorus, which can provide important information for further research on P. grandiflorus and lysine malonylation's role in environment stress, photosynthesis, and secondary metabolites enrichment.
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