Amino Acids最新文献

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.

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.

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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.

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.

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 (δ¹³C) 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 δ¹³C, indicating breastmilk consumption. Subtle changes in glutamate δ¹³C likely result from its ‘non-essential’ status. Additionally, δ¹³C 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 δ¹³C of amino acids may change over an individual’s lifespan or be altered due to various forms of stress.

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.

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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.

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.

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.