Amino Acids Tyrosine Research Articles

Elucidation of binding mechanism of rhodanine derivative P4OC on bovine serum albumin

Rhodanine is an important scaffold in medicinal chemistry and it act as potent anticancer agent and other pharmacological effects. In pharmacokinetics and pharmacodynamics studies of the drug, the drug binding properties on serum protein is crucial for producing better drug. This study was designed to explore the binding interactions between the Rhodanine derivative (P4OC) on Bovine Serum Albumin (BSA). The interactions between P4OC and BSA were investigated using biophysical approach and molecular docking. The quenching mechanism and binding constants of P4OC on BSA were determined by biophysical approach through fluorescence spectroscopic experiments. Circular dichroism (CD) spectroscopy was used to study the secondary structural changes of BSA upon P4OC binding. The fluorescence experiments of P4OC binding on BSA show good drug binding with static quenching constants using stern Volmer plot and found the quenching constant value K P4OC = 1.12762 × 1013 M−1 with corresponding binding free energy (ΔG) −2.303 kcal/mol. The molecular displacement fluorescence emission on BSA–P4OC complex by site specific markers shows that P4OC binds at I A sub-domain of BSA further confirmed peak shift by synchronous fluorescence of P4OC on BSA with tyrosine, tryptophan and phenylalanine amino acids. Increasing concentration of P4OC on BSA found secondary structural changes, the percentage of α-helix was decreased as well increase percentage of β-sheet and random coil. The binding of P4OC to BSA was computationally studied by molecular docking methods. Thus, results obtained are in excellent agreement with experimental and theoretical results with respect to the binding mechanism and binding constant of P4OC on BSA. We concluded that, the rhodanine derivative P4OC possesses good drug binding properties on BSA. Further P4OC may be evaluated its potential pharmacological activities on clinical trial. Communicated by Ramaswamy H. Sarma

Assessment of macronutrients dietary intake, central adiposity among pre- and postmenopausal Egyptian women with benign and malignant breast tumors

Breast cancer (BC) is the second most frequent cancer in women and the second most common cancer worldwide. Lifestyle factors, like body weight, physical activity and diet, may be accompanying with higher BC risk. The assessment of macronutrients dietary intake; protein, fat, carbohydrates and their components of amino, fatty acids, and central obesity/adiposity among pre- and postmenopausal Egyptian women with benign and malignant breast tumors. The current case control study included 222 women: 85 control, 54 benign and 83 breast cancer patients. Clinical, anthropocentric and biomedical examinations were performed. Dietary history and health attitude were done. The anthropometric parameters including waist circumference (WC) and the body mass index (BMI) of the benign and the women with malignant breast lesions showed the highest values when compared to the control (35.45±15.58km2 and 101.24±15.01cm, 31.39±6.77km2 and 98.85±13.53cm and 27.51±7.10km2 and 84.33±13.78cm). The biochemical parameters revealed high concentration of the total cholesterol (TC) (192.83±41.54mg/dl), low density lipoprotein-cholesterol (LDL-C) (117.88±35.18mg/dl) and the median insulin level 13.8 (10.2-24.1) μu/ml in the malignant patients with high significant difference compared to the control. The malignant patients had the highest daily caloric intake (795.84±519.95K calories) proteins (65.39±28.77g), total fats (69.09±32.15g) and carbohydrates (196.70±85.35g), when compared to the control. Data also revealed the high daily consumption of the different types of the fatty acids with high linoleic/linoleinic ratio among the malignant group (14.284±6.25). Branched chain amino acids (BGAAs), sulphur amino acids (SAAs), conditional amino acids (CAAs) and aromatic amino acids (AAAs) proved to be the highest in this group. Correlation coefficient between the risk factors revealed either positive or negative weak correlation except that between serum LDL-C concentration and the amino acids (isoleucine, valine cysteine, tryptophan and tyrosine) and negative association with the protective polyunsaturated fatty acids. Participants with breast cancer had the greatest levels of body fatness and unhealthy feeding habits relative to their high calorie, protein, carbohydrate, and fat intake.

Screening for Primordial RNA–Peptide Interactions Using High-Density Peptide Arrays

RNA-peptide interactions are an important factor in the origin of the modern mechanism of translation and the genetic code. Despite great progress in the bioinformatics of RNA-peptide interactions due to the rapid growth in the number of known RNA-protein complexes, there is no comprehensive experimental method to take into account the influence of individual amino acids on non-covalent RNA-peptide bonds. First, we designed the combinatorial libraries of primordial peptides according to the combinatorial fusion rules based on Watson-Crick mutations. Next, we used high-density peptide arrays to investigate the interaction of primordial peptides with their cognate homo-oligonucleotides. We calculated the interaction scores of individual peptide fragments and evaluated the influence of the peptide length and its composition on the strength of RNA binding. The analysis shows that the amino acids phenylalanine, tyrosine, and proline contribute significantly to the strong binding between peptides and homo-oligonucleotides, while the sum charge of the peptide does not have a significant effect. We discuss the physicochemical implications of the combinatorial fusion cascade, a hypothesis that follows from the amino acid partition used in the work.

Characterizing the Impact of Package Type on Beer Stability

The brewing industry is highly competitive, driving the importance of beer stability. Brewers use both aluminum cans and glass bottles to distribute products; however, a direct comparison of the impact of these two package types on beer stability has yet to be conducted. Here, a non-targeted metabolomics approach was used to characterize changes in the metabolite profile of amber ale (AA) and India pale ale (IPA) packaged in cans and bottles over a 6-month aging period. A strong correlation by package type was observed for AA but not for IPA over all time points. Baseline differences in amino acids (glycine, tyrosine, and asparagine) and esters (isobutyl isobutyrate, 2-methylbutyl butyrate, and ethyl decanoate) were also observed in AA. Hop terpenes (humulene, pinocarvone, and α-calacorene) demonstrated package-dependent changes over time which appear to be influenced by metabolite water solubility. Overall, the results demonstrate that beer metabolites, and thus stability, are significantly impacted by package type.

L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress

Lactoferrin (LF) is a multifunctional antimicrobial, anti-inflammatory, and antioxidant protein that occurs naturally in mammals, most notably in exocrine gland tissues and fluids, such as in the eye. Nitrosative stress can promote changes to tyrosine and other amino acid residues of the protein, which also reduces the activity of LF. l-ergothioneine (ET) is a potent anti-inflammatory antioxidant present in the eye and other tissues through nutrition or supplementation and that may play a role in the prevention or treatment of a variety of diseases. Here we investigated the ability of ET to reduce 3-nitrotyrosine (NTyr) formation using two separate substrates, with the goal of determining whether ET can protect the antibacterial function of LF and other proteins when exposed separately to peroxynitrite and tetranitromethane as nitrating reagents. Native human LF was used as a simple protein substrate, and lamb corneal lysate was chosen as one example of mammalian tissue with a more complex mixture of proteins and other biomolecules. Nitration was monitored by absorbance and fluorescence spectroscopy as well as sandwich (nitrated LF) and direct NTyr (corneal lysate) enzyme-linked immunosorbent assays (ELISAs). We found that pretreatment with ET reduced chemical modification of both native LF and corneal lysate samples and loss of antibacterial LF function due to exposure to the nitrating reagents. These initial results suggest that ET, raised to sufficiently elevated levels, could be tailored as a therapeutic agent to reduce effects of nitrosative stress on LF and in turn sustain the protein activity.

Hereditary Tyrosinemia Type 1 Mice under Continuous Nitisinone Treatment Display Remnants of an Uncorrected Liver Disease Phenotype

Hereditary tyrosinemia type 1 (HT1) is a genetic disorder of the tyrosine degradation pathway (TIMD) with unmet therapeutic needs. HT1 patients are unable to fully break down the amino acid tyrosine due to a deficient fumarylacetoacetate hydrolase (FAH) enzyme and, therefore, accumulate toxic tyrosine intermediates. If left untreated, they experience hepatic failure with comorbidities involving the renal and neurological system and the development of hepatocellular carcinoma (HCC). Nitisinone (NTBC), a potent inhibitor of the 4-hydroxyphenylpyruvate dioxygenase (HPD) enzyme, rescues HT1 patients from severe illness and death. However, despite its demonstrated benefits, HT1 patients under continuous NTBC therapy are at risk to develop HCC and adverse reactions in the eye, blood and lymphatic system, the mechanism of which is poorly understood. Moreover, NTBC does not restore the enzymatic defects inflicted by the disease nor does it cure HT1. Here, the changes in molecular pathways associated to the development and progression of HT1-driven liver disease that remains uncorrected under NTBC therapy were investigated using whole transcriptome analyses on the livers of Fah- and Hgd-deficient mice under continuous NTBC therapy and after seven days of NTBC therapy discontinuation. Alkaptonuria (AKU) was used as a tyrosine-inherited metabolic disorder reference disease with non-hepatic manifestations. The differentially expressed genes were enriched in toxicological gene classes related to liver disease, liver damage, liver regeneration and liver cancer, in particular HCC. Most importantly, a set of 25 genes related to liver disease and HCC development was identified that was differentially regulated in HT1 vs. AKU mouse livers under NTBC therapy. Some of those were further modulated upon NTBC therapy discontinuation in HT1 but not in AKU livers. Altogether, our data indicate that NTBC therapy does not completely resolves HT1-driven liver disease and supports the sustained risk to develop HCC over time as different HCC markers, including Moxd1, Saa, Mt, Dbp and Cxcl1, were significantly increased under NTBC.

Fibroblast growth factor 5 (FGF5) and its missense mutant FGF5-H174 underlying trichomegaly: a molecular dynamics simulation investigation

The missense mutation Y174H of FGF5 (FGF5-H174) had been associated with trichomegaly, characterized by abnormally long and pigmented eyelashes. The amino acid tyrosine (Tyr/Y) at position 174 is conserved across many species, proposedly holding important characteristics for the functions of FGF5. Microsecond molecular dynamics simulations along with protein-protein docking and residue interacting network analysis were employed to investigate the structural dynamics and binding mode of both wild-type (FGF5-WT) and its mutated counterpart (FGF5-H174). It was found that the mutation decreased number of hydrogen bonds within the protein, sheet secondary structure, interaction of residue 174 with other residues, and number of salt-bridges. On the other hand, the mutation increased solvent accessible surface area, number of hydrogen bonds between the protein and solvent, coil secondary structure, protein C-alpha backbone root mean square deviation, protein residue root mean square fluctuations, as well as occupied conformational space. In addition, protein-protein docking integrated with molecular dynamics simulations and molecular mechanics - Poisson-Boltzmann surface area (MM/PBSA) binding energy calculation demonstrated that the mutated variant possessed stronger binding affinity towards fibroblast growth factor receptor 1 (FGFR1). However, residue interaction network analysis demonstrated that the binding mode of the FGFR1-FGF5-H174 complex was drastically different from that of the FGFR1-FGF5-WT complex. In conclusion, the missense mutation conferred more instability within itself and stronger binding affinity towards FGFR1 with distinctively altered binding mode or residue connectivity. These findings might help explain the decreased pharmacological activity of FGF5-H174 towards FGFR1, underlying trichomegaly. Communicated by Ramaswamy H. Sarma

Comparative Study and the Optimum Conditions On the Use of Certain Bacterial Strains For the Production of Some Amino Acids

This study aims to use some strains (Corynebacterium glutamicum, Lactobacillus bulgaricus, and Brevibacterium linens for the production of some amino acids (lysine, methionine, threonine, arginine, tyrosine, aspartic acid, glutamic acid, alanine, and proline) on synthetic fermentation media under different conditions (incubation periods; incubation temperatures; pH values; media volume and different sources of carbon and nitrogen) on the course of fermentation reactions of amino acids, and then quantitative analysis of amino acids by HPLC for choose the best conditions for increasing production of amino acids. The results showed that in the best conditions for three strains, the highest production of amino acids was recorded for Brevibacterium linens the pH (7.5), incubation temperature (30°C), medium volume (50 ml), and incubation period (48 hr), while for Corynebacterium glutamicum observed on pH (7), incubation temperature (30°C), medium volume (50 ml) and incubation period (48 hr), however, for Lactobacillus bulgaricus observed on pH 6.5, incubation temperature 37°C, medium volume (50 ml) and incubation period (48 hr). The best carbon and nitrogen sources were recorded for glucose and ammonium sulfate for three tested strains.

Comparison of characteristics between peptides in fish meat and fermented products

In the pasca of the COVID-19 pandemic, many researchers have focused on finding drugs for the COVID-19. Peptide research is predicted to have a physiological mechanism of action and it does not cause side effects, therefore it is necessary to search for peptide sources. The aim of this study was to characterize peptides extracted from tamban fish (Sardinella fimbriata) and fermented products (Cincalok of Tanjungpinang). Peptide extract was obtained by maceration extraction using 95% PA (1:5) ethanol solvent, and then it filtered using MWCO 3 kDa and 10 kDa. The amino acid characteristics of the peptides was obtained using HPLC. Peptides of tamban fish had the pH of 7.6 and they are rich of amino acid histidine (890.18 mg/L), in addition to the amino acids glutamate, tyrosine, glycine, leucine, alanine, and aspartic acid. But the peptides of the fermented cincalok product had the pH of 6.4 and they are rich of amino acid leucine (1066.83 mg/L), in addition to the amino acids glutamate, valine, isoleucine, and alanine. Each of these peptides had the molecular weight of 10 kDa. The results of this study can be used as preliminary information to the pharmaceutical development of a new source of peptides.

Abstract P197: HbA1c Partially Mediates the Effect of Tyrosine and Phenylalanine on Incident Myocardial Infarction

Introduction: The aromatic amino acids tyrosine and phenylalanine may increase type 2 diabetes risk, but few studies have examined whether these critical molecular precursors exert additional phenotypic effects and whether these effects are independent of insulin resistance. We evaluated associations between two aromatic amino acids - tyrosine and phenylalanine - with a broad range of phenotypic categories in the UK Biobank using polygenic risk score (PRS) instrumental variables that are robust to confounding and reverse causation and tested for mediation by glycated hemoglobin (HbA1c) as a measure of insulin resistance. Hypothesis: We hypothesized that tyrosine and phenylalanine would show broad phenotypic effects and that many of these effects would be mediated by HbA1c. Methods: We constructed PRS (Crosspred) using all nominally significant and common (minor allele frequency >5%) variants from genome-wide association studies (SAIGE) of unrelated European ancestry participants in the UK Biobank. We evaluated associations with 273 curated phenotypes spanning 20 categories, including endocrine, circulatory, and cancer related traits. We corrected for multiple comparisons using false discovery rate <0.05. Mediation by HbA1c was estimated using the CMAverse package in R, controlling for age, sex, center, ancestral principal components, body mass index, and socioeconomic status. Results: A total of 108,554 participants had tyrosine or phenylalanine measured at baseline (mean age=57 years; 54% (58,880/108,554) female). PRS were predictive of tyrosine (R 2 =0.28) and phenylalanine (R 2 =0.26). Tyrosine and phenylalanine PRS showed significant associations with 121/273 (44%) and 124/273 (45%) of phenotypes, respectively, including chronic kidney disease, serum testosterone, lymphocyte count, and myocardial infarction (MI; n=3,349 cases, mean years of follow-up=11). For incident MI, every one standard deviation increase in the tyrosine PRS increased the odds of MI by 4.4% (total effect odds ratio (OR) = 1.044 (95% confidence interval (CI): 1.002, 1.089). The direct effect of the tyrosine PRS on incident MI was slightly decreased (OR= 1.040 (95% CI: 0.997, 1.084) when extending the statistical model to examine mediation by HbA1c, with an estimated indirect effect of 1.004 (95% CI: 1.003, 1.006) and an estimated percent mediated by HbA1c of 9.95% (95% CI: -0.04%, 19.90%). Findings were consistent for phenylalanine, where the percent of the total effect mediated by HbA1c was 8.94% (95% CI: -1.93, 19.80%). Conclusions: The effect of tyrosine and phenylalanine on incident MI may primarily operate through pathways other than glucose dysregulation.

Investigating the biophysical interaction of serum albumins-gold nanorods using hybrid spectroscopic and computational approaches with the intent of enhancing cytotoxicity efficiency of targeted drug delivery

In this contribution, biophysical aspects of binding interaction, conformational changes, and molecular simulation studies of human and bovine serum albumins (HSA and BSA) exposed to gold nanorods (AuNRs) are thoroughly investigated and their bio-nanoconjugates were then used in in-vitro cytotoxic studies. The structural variations of AuNRs in the presence of serum proteins were confirmed by absorbance and high-resolution transmission electron microscopic (HR-TEM) pictures. According to the results of the steady-state emission quenching, AuNRs affect the intrinsic emission of HSA and BSA by a static mechanism. Synchronous emission spectrum results showed that the microenvironment near the tryptophan and tyrosine amino acid residues of serum proteins is altered, and the impact is stronger toward tryptophan than tyrosine. Furthermore, it was demonstrated by infrared, absorbance, and three-dimensional (3D) luminescence spectroscopic methods that the binding of AuNRs can arouse concerns and cause changes in the structural and/or microenvironmental characteristics of HSA and BSA. An outcome of the computational molecular simulation study supports the stability of the bio-nanoconjugate, and molecular docking interaction investigations suggest that the two-dimensional AuNRs surface associated with the cysteine residue of HSA and BSA contains sulphur atoms. Furthermore, using an in vitro model using the A-549 and MCF-7 cell lines, we calculated the toxicity and the effectiveness of cellular absorption of the AuNRs and their bio-nanoconjugates as a function of supplied dosage. These cytotoxicity findings demonstrate that protein adsorption affects AuNRs' physicochemical characteristics as well as enhances their subsequent biological function.

In Silico study and design of some new potent threonine tyrosine kinase inhibitors using molecular docking simulation

ABSTRACT Threonine tyrosine kinase (TTK) is one of the most important members of kinase enzymes and has a major role in the phosphorylation of threonine and tyrosine amino acids in proteins. TTK can cause some important diseases, such as Alzheimer, cancers and cardio diseases. Nowadays, In Silico study and evaluation are applied through virtual screening tools, such as molecular docking simulations and predictions of ADMET-related properties to investigate new potent inhibitors of this target protein. The molecular docking simulation is performed to achieve the best binding affinity and docking scores. This is done by comparison between the standard inhibitor and high-scoring selected ligands. After evaluation of Molecular docking results and ADMET related properties, N-(cyclopropylmethyl)-5-(4-methylphenyl)imidazo[1,2-a]pyrazin-8-amine (L5 table 1), 3-[4-[1-(cyclopropylamino)ethenyl]phenyl]-N-(2-methylpropyl)imidazo[1,2-a]pyrazin-8-amine (L2 table 1), (Z)-1-[(E)-[(Z)-1-[7-(aminomethyl)-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]but-2-enylidene]amino]-N-(cyclopropylmethyl)prop-1-en-1-amine were indicated as new TTK potent inhibitors.

Spectrofluorimetric methods for the determination of mirabegron by quenching tyrosine and L-tryptophan fluorophores: Recognition of quenching mechanism by stern volmer relationship, evaluation of binding constants and binding sites

Green spectrofluorimetric methods have been adopted for the determination of Mirabegron (MG) in pure drug and pharmaceutical dosage form. The developed methods based on fluorescence quenching of tyrosine and L-tryptophan amino acids fluorophores by the effect of Mirabegron as a quencher. Experimental conditions of the reaction were studied and optimized. The Fluorescence quenching (ΔF) values were proportional to the concentration range of MG 2–20 μg/ml for the tyrosine-MG system in buffered media pH 2 and 1–30 μg/ml for L-tryptophan-MG system pH 6. Good correlation coefficients with low detection limits of 0.163 and 0.234 μg/ml for the two systems respectively. Method validation was applied according to ICH guidelines. The cited methods were successively applied for MG determination in tablet formulation. No statistically significant difference between the results of the cited and the reference methods regarding t and F tests. The proposed spectrofluorimetric methods are simple, rapid, eco-friendly and can contribute to MG’s methodologies in quality control labs. Stern-Volmer relationship, the effect of temperature, quenching constant (Kq), and UV spectra were studied to identify the mechanism by which the quenching might occur. The results demonstrated that fluorescence quenching of tyrosine was a dynamic quenching process and L-tryptophan was static. The double log plots were constructed to determine the binding constants and binding sites. The greenness profile of the developed methods has been assessed by Green Analytical procedure index (GAPI) and Analytical Greenness Metric Approach (AGREE).

Novel poly(ester amide) derived from tyrosine amino acid for targeted pulmonary drug delivery of fluticasone propionate

AbstractNanoaggregates made from amino acid‐based polymers have been an important platform for targeted drug delivery systems such as the lungs. Therefore, the aim of the present study is to develop tyrosine‐based poly(ester amide)s (Tyr‐PEA) for dry powder inhaler (DPI) of a potent drug (fluticasone propionate [FP]) using interfacial polymerization. The molecular and surface profiling characteristics were evaluated using Fourier‐transformed infrared spectroscopy, X‐ray diffraction, transmission electron microscopy, particle size analysis, nuclear magnetic resonance, differential scanning calorimetry, and scanning electron micrographs. The aerodynamic performance was evaluated using the NGI. The results confirmed the formation of the PEA and FP‐loaded Tyr‐PEA with an average particle size of, 45.39 ± 6.32 nm. The produced FP/Tyr‐PEA showed entrapment efficiency and encapsulation capacity of FP of 92.32% and 0.526% respectively, which enabled the delivery of this potent drug in a reasonable dose. The in‐vitro performance of the FP‐loaded PEA was compared to a marketed product and results revealed a significant enhancement of the emitted dose (87.29% vs. 59% respectively [t‐test, p < 0.05]). FP‐loaded Tyr‐PEA produced a higher respirable dose when compared to the marketed FP DPI (48.63 μg vs. 34.15 μg). Overall, FP‐loaded Tyr‐PEA was successfully prepared with optimal performance. Tyr‐PEA‐based nanoparticles provide a potential platform for targeted drug delivery, particularly potent actives.

Direct identification of amino acid-derived hormones with single-atom resolution using an engineered aerolysin nanopore.

The amino acid-derived hormones (AAHs), which are relatively small hydrophobic molecules derived from the amino acid tyrosine and tryptophan, play critical roles in the regulation of organism development and metabolism process. Direct identification of AAHs and their metabolites is highly desirable but very challenging because they simultaneously possess the features of small volume, hydrophobicity and highly structural similarity. Nanopore, capable of sensing the analytes in a single-molecule manner, may be engineered to identity AAHs. The key aporia is the ion current instability caused by the introduction of hydrophobic amino acids inside the nanopore confinement that is essential to improve the spatial and temporal resolution for small hydrophobic molecules sensing. Herein, we design a mutant aerolysin that precisely introduces a hydrophobic chemical environment in the critical sensing region with a highly controlled hydrogen bonds network to balance the ion follow stability and hydrophobic interactions. With this hydrophobic enhanced aerolysin nanopore, direct identification of AAHs was achieved, including thyroid hormone, pineal hormone and adrenal medullary hormone. Furthermore, three thyroid hormones with single iodine atom difference (T4, T3, and T2), were observed to be clearly discriminated in their mixture. Our engineered nanopore can even distinguish isomers of T3 and rT3 that vary only slightly in structure. Assisted with a custom clustering machine learning algorithm, the thyroid hormones T4, T3, and T2 in their mixture could be quantified, which suggests a simple and rare approach to measure the AAHs in clinical samples.

Impacts of dibutyl phthalate on bacterial community composition and carbon and nitrogen metabolic pathways in a municipal wastewater treatment system

Dibutyl phthalate (DBP) is a typical toxic and hazardous pollutant in pharmaceutical wastewater, affecting the metabolism of microbial flora, leading to decreased treatment efficiency, and deteriorated effluent quality in municipal wastewater treatment plants (WWTPs). This study conducted a long-term experiment with 6 operational stages in a pilot-scale A2O-MBR system, analyzing the effect of DBP on the bacterial community and their carbon and nitrogen metabolic pathways. 16S rRNA gene amplicon sequencing analysis and principal components analysis (PCA) showed that DBP at 8 mg/L significantly influenced the structure of bacterial community (P < 0.05), resulting in reduced bacterial community diversity. Metagenomic analysis was used to explore the embedded carbon and nitrogen metabolic pathways. At the presence of DBP, the metabolism of saccharides, lipids, and aromatic compounds were blocked owing to the vanishment of key enzyme (such as acetylaminohexosyltransferase (EC 2.4.1.92) and UDP-sugar pyro phosphorylase (EC 2.7.7.64)) encoding genes, resulting in weakened carbon metabolism, and thus reduced COD removal performance. The resultant deficiency of the genes such as those encoding hydroxyproline dehydrogenase (EC 1.5.5.3) gave rise to interrupted metabolic pathways of amino acid (arginine, proline, tyrosine, and tryptophan), resulting in declined function of nitrogen metabolism and thus reduced TN removal efficiency. The uncovery of the mechanisms by which DBP affects wastewater treatment system efficiency and microbial metabolism is of theoretical importance for the efficient operation of municipal and pharmaceutical wastewater treatment systems.

A Metabolomics-Based Investigation of the Effects of a Short-Term Body Weight Reduction Program in a Cohort of Adolescents with Obesity: A Prospective Interventional Clinical Study.

Metabolomics applied to assess the response to a body weight reduction program (BWRP) may generate valuable information concerning the biochemical mechanisms/pathways underlying the BWRP-induced cardiometabolic benefits. The aim of the present study was to establish the BWRP-induced changes in the metabolomic profile that characterizes the obese condition. In particular, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to determine a total of 188 endogenous metabolites in the plasma samples of a cohort of 42 adolescents with obesity (female/male = 32/10; age = 15.94 ± 1.33 year; body mass index standard deviation score (BMI SDS) = 2.96 ± 0.46) who underwent a 3-week BWRP, including hypocaloric diet, physical exercise, nutritional education, and psychological support. The BWRP was capable of significantly improving body composition (e.g., BMI SDS, p < 0.0001), glucometabolic homeostasis (e.g., glucose, p < 0.0001), and cardiovascular function (e.g., diastolic blood pressure, p = 0.016). A total of 64 metabolites were significantly reduced after the intervention (at least p < 0.05), including 53 glycerophospholipids (23 PCs ae, 21 PCs aa, and 9 lysoPCs), 7 amino acids (tyrosine, phenylalanine, arginine, citrulline, tryptophan, glutamic acid, and leucine), the biogenic amine kynurenine, 2 sphingomyelins, and (free) carnitine (C0). On the contrary, three metabolites were significantly increased after the intervention (at least p < 0.05)-in particular, glutamine, trans-4-hydroxyproline, and the octadecenoyl-carnitine (C18:1). In conclusion, when administered to adolescents with obesity, a short-term BWRP is capable of changing the metabolomic profile in the plasma.

Role of Impaired Glycolysis in Perturbations of Amino Acid Metabolism in Diabetes Mellitus.

The most frequent alterations in plasma amino acid concentrations in type 1 and type 2 diabetes are decreased L-serine and increased branched-chain amino acid (BCAA; valine, leucine, and isoleucine) levels. The likely cause of L-serine deficiency is decreased synthesis of 3-phosphoglycerate, the main endogenous precursor of L-serine, due to impaired glycolysis. The BCAA levels increase due to decreased supply of pyruvate and oxaloacetate from glycolysis, enhanced supply of NADH + H+ from beta-oxidation, and subsequent decrease in the flux through the citric acid cycle in muscles. These alterations decrease the supply of α-ketoglutarate for BCAA transamination and the activity of branched-chain keto acid dehydrogenase, the rate-limiting enzyme in BCAA catabolism. L-serine deficiency contributes to decreased synthesis of phospholipids and increased synthesis of deoxysphinganines, which play a role in diabetic neuropathy, impaired homocysteine disposal, and glycine deficiency. Enhanced BCAA levels contribute to increased levels of aromatic amino acids (phenylalanine, tyrosine, and tryptophan), insulin resistance, and accumulation of various metabolites, whose influence on diabetes progression is not clear. It is concluded that amino acid concentrations should be monitored in patients with diabetes, and systematic investigation is needed to examine the effects of L-serine and glycine supplementation on diabetes progression when these amino acids are decreased.

Perception of the interaction behavior between pepsin and the antimicrobial drug secnidazole with combined experimental spectroscopy and computer-aided techniques

Drug-pepsin interaction possibly affects pepsin activity, leads to undesirable shift of its functionality, and likely induces adverse effects in the gastrointestinal tract. The present study aims at exploring the interaction of pepsin with the antiprotozoal/antibacterial drug secnidazole adopting a combination of experimental spectroscopy and computational techniques. For this purpose, different spectroscopic methods including fluorescence, synchronous fluorescence, UV–Visible absorption, and infrared spectroscopy were adopted and coordinated with in silico analysis via molecular docking. The employed synchronized approaches evidenced that; pepsin interacted with secnidazole via static mechanism at stomach pH inferring some consequent conformational changes in the structure of pepsin. Thermodynamic study of drug-pepsin interaction demonstrated that the interaction is spontaneous via van der Waals and hydrogen bonding interaction and the orientation of ligand within pepsin cavity was illustrated by molecular docking. The synchronous fluorescence study proved that tyrosine amino acid residues were involved in the interaction more than tryptophan amino acid residues. Eventually, the combined experimental and molecular docking approaches suggest that secnidazole interacts with pepsin and alter its structure, that finding correlates to gastrointestinal side effects related to secnidazole oral administration.

Linking chemical exposure and fish metabolome: Discovering new biomarkers of environmental exposure of Argyrosomus regius to the antidepressant venlafaxine

In this study, a non-target metabolomic approach was used to investigate changes in the metabolome of juvenile meagre (Argyrosomus regius) exposed to venlafaxine (20 µg/L). A total of 24, 22 and 8 endogenous metabolites tentatively identified in liver, brain and plasma, respectively, were significantly changed in venlafaxine exposed meagre, showing tissue-dependent variations in the metabolic profile. The amino acids tryptophan, tyrosine and phenylalanine, which are related to the synthesis, availability, and expression of neurotransmitters (e.g., serotonin, dopamine, epinephrine), showed to be dysregulated by venlafaxine exposure. A high impact was observed in fish brain metabolome that showed a trend of up-regulation for most of the tentatively identified metabolites. In conclusion, the identification of possible biomarkers of exposure in fish metabolome to environmental stressors such as venlafaxine is crucial to assess early signal changes at molecular level, enabling the prevention of deleterious effects at the organism and population levels.