Amino Acids最新文献

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.

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.

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.

Canola protein is a rapeseed-derived protein that contains all essential amino acids in proportions that meet the WHO amino acid scoring requirements, making it an interesting protein for human food applications. It is currently unknown whether canola protein processing modulates postprandial plasma amino acid bioavailability in vivo in humans. This study compared postprandial plasma amino acid profiles following the ingestion of unprocessed (native) canola, processed canola, and whey protein isolate in healthy, young, females. In a randomized, clinical, cross-over design, 15 healthy young females (25 ± 3 y) participated in four test days on which they consumed 20 g protein as either native canola, enzyme processed or heat processed canola protein, or 20 g whey protein. Blood samples were collected for 5 h following protein ingestion to assess plasma amino acid concentrations. Ingestion of native canola protein resulted in lower increases in plasma total amino acid (TAA) concentrations compared to whey protein (3191 ± 794 vs. 4429 ± 84 µmol∙L^− 1, P < 0.001). Canola protein processing resulted in greater peak plasma total amino acids concentrations, reaching statistical significance for enzyme (3599 ± 687 µmol∙L^− 1, P = 0.045) but not heat (3565 ± 722 µmol∙L^− 1, P = 0.166) treated compared to native canola protein. Plasma total amino acid availability, expressed as incremental area under the curve over a 5 h postprandial period, did not differ between treatments and averaged 163 ± 81, 171 ± 76, 194 ± 82, and 207 ± 85 mmol∙300 min∙L^− 1 following ingestion of native, enzyme- and heat processed canola, and whey protein, respectively (P > 0.05). Ingestion of whey protein allows for a more rapid postprandial rise in circulating essential and non-essential amino acids and greater postprandial plasma total amino acid availability when compared to the ingestion of native canola protein. Ingestion of enzyme- or heat processed canola protein accelerates the postprandial rise in circulating amino acids but does not further augment overall plasma amino acid availability throughout a 5 h postprandial period when compared to the ingestion of native canola protein.

Claudin (CLDN) proteins are extensively studied due to their critical role in maintaining tissue barriers and cell polarity. However, significant gaps remain in understanding the functional mechanisms of their sequence motifs and the molecular mechanisms of their interactions with other tight junction proteins. This review systematically examines the multifunctional properties of the CLDN protein family from the perspectives of sequence and structure. During evolution, CLDN family members have developed highly conserved structural features, particularly key conserved sites within the first extracellular loop (ECL1) and the C-terminal PDZ-binding domain, which play a central role in regulating the barrier function of tight junctions, ion selectivity, and protein–protein interactions. Furthermore, the distribution pattern of acidic and basic amino acids in ECL1 has been shown to directly determine ion selectivity and paracellular permeability. Meanwhile, the assembly and functional stability of tight junctions are precisely regulated by the C-terminal PDZ-binding domain through its interactions with the ZO protein family. Additionally, the study further elucidates how CLDN proteins modulate critical signaling pathways governing cellular proliferation, survival, and permeability, thereby participating in diverse physiological and pathological processes. These insights have deepened the understanding of the functional diversity of CLDN proteins and provided a new theoretical basis for developing disease diagnostic markers and designing targeted treatment strategies based on CLDN proteins.

The X-ray repair cross-complementary group 1 (XRCC1) gene 399 codon polymorphism may alter the structure of DNA repair enzymes to regulate DNA repair capacity. Impaired DNA repair ability can lead to the development of cancers such as prostate cancer (PCa). Although the association between the XRCC1 codon 399 polymorphism and the risk of PCa has been widely reported, the results have not been clear. Data were collected from PubMed, EMBASE, the Wanfang Database, CNKI and the Web of Science. A total of 20 case‒control studies were selected for inclusion in this updated analysis to determine the association between the XRCC1 codon 399 polymorphism and the risk of PCa. The crude odds ratio (OR) and 95% confidence interval (CI) were calculated using Stata (version 18) software to evaluate the association between the XRCC1-Arg399Gln polymorphism and prostate cancer. We identified 20 eligible reports that included 5803 cases of prostate cancer and 5470 controls. Our meta-analysis revealed a significant association between the XRCC1-Arg399Gln polymorphism and the risk of prostate cancer. In particular, according to the recessive models, this polymorphism was associated with a significantly increased prevalence of prostate cancer in Asian populations (AA versus AG + GG: OR = 1.255, 95% CI = 1.063–1.481, P = 0.507, I², < 25%). Based on these results, the XRCC1-Arg399Gln polymorphism may be a risk factor for prostate cancer and can be used as a biomarker to predict the prognosis of prostate cancer.

The present work describes the protolytic properties and in vitro biological activity of spinorphin (Leu-Val-Val-Tyr-Pro-Trp-Thr) and three spinorphin derivatives containing butyric acid residue: Butyryl-Lys-Lys-Leu-Leu-Val-Tyr-Pro-Trp-Thr, Butyryl-Lys-Lys-Leu-Val-Val-Tyr-Pro-Trp-Thr (butyric acid bound to the α-amino group of lysine), Lys(Butyryl)-Lys-Leu-Val-Val-Tyr-Pro-Trp-Thr (butyric acid bound to the ε-amino group of lysine) in an aqueous solution. The overall protonation constants and the stepwise dissociation constants of the ligands studied were calculated by the potentiometric method. The percentage of each species formed was estimated from the species distribution curves as a function of pH. The biological activity of all tested compounds was characterized in vitro, in the neutral red uptake and Griess assay tests in RAW264.7 macrophage cell line. The three protonation constants for spinorphin and four for its derivatives suggest that metal ions may bind to these peptides and form complexes by coordination with the functional groups of the respective amino acid residues. In vitro biological activity tests suggest that two peptides deserve attention for their potential anti-inflammatory role.

The overuse of antibiotics has led to a growing crisis—antimicrobial resistance, making it harder to treat infections and pushing scientists to find new solutions. Among the most promising alternatives are bioactive peptides, especially antimicrobial peptides, which offer broad-spectrum activity with a lower risk of resistance. One exciting source of these peptides is milk, particularly casein-derived peptides, which naturally possess antimicrobial properties. This study focused on bovine milk casein to design and synthesize a novel antimicrobial peptide. We evaluated several properties, such as antimicrobial activity, cytotoxicity, stability, and structure, using computational predictions to select the most promising candidate. The peptide NCP1 emerged as the best option and was synthesized for lab testing. Our results showed that NCP1 has antifungal activity and effectively stops the growth of Candida albicans with a minimum fungicidal concentration (MFC) of 250 µg/mL in less than four hours. It also prevented biofilm formation, interacted with DNA, and bound to ergosterol, ultimately damaging the fungal cell wall. Additionally, NCP1 demonstrated feeble antibacterial effects, particularly against Staphylococcus aureus and Pseudomonas aeruginosa. However, its antibacterial impact weakened over time due to interactions with environmental salts. Since the NCP1 peptide has low cytotoxicity and kills the yeasts selectively, further refinements to improve its potency and stability could pave the way for our future study of the presentation of a potent antimicrobial peptide.

Diabetic retinopathy, a leading cause of vision loss in working-age populations, is a severe complication of diabetes mellitus. Metabolomics, a key approach in systems biology, offers insights into the complex pathophysiology of diabetes by analyzing low-molecular-weight compounds in biological contexts. This study investigated metabolite alterations in the aqueous humor of diabetic and non-diabetic patients undergoing cataract surgery to identify potential biomarkers associated with diabetes. Aqueous humor samples from 191 patients (48 diabetic, 143 non-diabetic) were analyzed using targeted liquid chromatography-mass spectrometry. Metabolite data were normalized and statistically evaluated using univariate analysis, including fold change calculations, t-tests, and volcano plots. Pathway enrichment analysis was performed using KEGG, SMPDB, and RaMP-DP databases. Key findings revealed differential abundance of several metabolites, including upregulated 3-hydroxykynurenine, histamine, and octanoylcarnitine, and downregulated putrescine in diabetic patients. Although some metabolites exhibited low p-values (< 0.05), high FDR limited the statistical robustness of these findings. Quantitative enrichment analysis suggested potential involvement of the kynurenine pathway and tryptophan catabolism in diabetes-related metabolic changes. The study highlights the potential roles of these metabolites in diabetes-related ocular changes, supported by prior research linking them to oxidative stress, inflammation, and metabolic dysregulation. Antioxidative therapies targeting diabetes-associated metabolic alterations may offer potential for mitigating diabetes-related complications. High FDR underscores the need for cautious interpretation and further validation in larger cohorts. Future studies should focus on longitudinal analyses and mechanistic investigations to clarify the diagnostic and prognostic potential of these metabolites in diabetic retinopathy and other diabetes-related complications.

Anal fissure causes pain and bleeding during or after bowel movements, significantly impacting individuals’ quality of life. Current treatments aim to interrupt this cycle but have associated risks and limitations. The emergence of arginine, crucial for protein creation and nitric oxide (NO) production, presents an intriguing therapeutic avenue by the impact on reducing anal sphincter pressure and enhancing anoderm blood flow, due to its roles in vasodilation, anti-inflammatory responses, and collagen synthesis, which can promote wound healing and highlighting its potential as an alternative therapy. However, the effectiveness of oral supplementation remains debated, indicating the need for further elucidation of its mechanisms. Its multifaceted mechanisms can present an exciting avenue for nuanced treatments, urging further exploration to refine its role in chronic anal fissure management. This review comprehensively explores the therapeutic landscape of L-arginine in chronic anal fissure management, integrating recent research studies and clinical investigations.