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1.
Food Chem ; 462: 140972, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39208720

RESUMO

Field pea seeds have long been recognized as valuable feed ingredients for animal diets, due to their high-quality protein and starch digestibility. However, the chemical composition of pea cultivars can vary across different growing locations, consequently impacting their nutrient profiles. This study employs untargeted metabolomics in conjunction with the quantification of fatty acids and amino acids to explore the influence of three different growing locations in Spain (namely Andalusia, Aragon and Asturias), on the nutritional characteristics of seeds of various pea cultivars. Significant interactions between cultivar and environment were observed, with 121 metabolites distinguishing pea profiles. Lipids, lipid-like molecules, phenylpropanoids, polyketides, carbohydrates, and amino acids were the most affected metabolites. Fatty acid profiles varied across locations, with higher C16:0, C18:0, and 18:1 n-9 concentration in Aragón, while C18:2 n-6 predominated in Asturias and C18:3 n-3 in Andalusia. Amino acid content was also location-dependent, with higher levels in Asturias. These findings underscore the impact of environmental factors on pea metabolite profiles and emphasize the importance of selecting pea cultivars based on specific locations and animal requirements. Enhanced collaboration between research and industry is crucial for optimizing pea cultivation for animal feed production.


Assuntos
Aminoácidos , Ração Animal , Ácidos Graxos , Valor Nutritivo , Pisum sativum , Sementes , Pisum sativum/metabolismo , Pisum sativum/química , Pisum sativum/crescimento & desenvolvimento , Ração Animal/análise , Aminoácidos/metabolismo , Aminoácidos/análise , Sementes/química , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Ácidos Graxos/metabolismo , Ácidos Graxos/análise , Animais , Espanha , Metabolômica
2.
Food Chem ; 462: 140967, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39208726

RESUMO

This study examined the impact of live bread yeast (Saccharomyces cerevisiae) on the nutritional characteristics of Asian dried noodles. Micronutrient analysis of fermented noodles revealed a 6.9% increase in the overall amino acid content, a 37.1% increase in the vitamin B content and a 63.0% decrease in the phytic acid level. Molecular weight analysis of starch and protein contents revealed moderate decrease in the fermented noodles. The in vitro digestion of fermented noodles showed a slightly faster initial acidification, four-fold decrease in the initial shear viscosity (from 8.85 to 1.94 Pa·s). The initial large food particle count (>2 mm diameter) was 19.5% lower in the fermented noodles. The fermented noodles contained slightly higher free sugar content (73.5 mg g-1 noodle) during the gastric digestion phase. The overall nutrition and digestion results indicate nutritional improvement and digestion-easing attributes in the fermented noodles.


Assuntos
Digestão , Fermentação , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/química , Nutrientes/metabolismo , Nutrientes/análise , Humanos , Aminoácidos/metabolismo , Aminoácidos/análise , Pão/análise , Pão/microbiologia , Modelos Biológicos , China , População do Leste Asiático
3.
Methods Mol Biol ; 2855: 85-101, 2025.
Artigo em Inglês | MEDLINE | ID: mdl-39354302

RESUMO

Chiral metabolomics entails the enantioselective measurement of the metabolome present in a biological system. Over recent years, it has garnered significant interest for its potential in discovering disease biomarkers and aiding clinical diagnostics. D-Amino acids and D-hydroxy acids, traditionally overlooked as unnatural, are now emerging as novel signaling molecules and potential biomarkers for a range of metabolic disorders, brain diseases, kidney disease, diabetes, and cancer. Despite their significance, simultaneous measurements of multiple classes of chiral metabolites in a biological system remain challenging. Hence, limited information is available regarding the metabolic pathways responsible for synthesizing D-amino/hydroxy acid and their associated pathophysiological mechanisms in various diseases. Capitalizing on recent advancements in sensitive analytical techniques, researchers have developed various targeted chiral metabolomic methods for the analysis of chiral biomarkers. Here, we highlight the pivotal role of chiral metabolic profiling studies in disease diagnosis, prognosis, and therapeutic interventions. Furthermore, we describe cutting-edge chromatographic and mass spectrometry methods that enable enantioselective analysis of chiral metabolites. These advanced techniques are instrumental in unraveling the complexities of disease biomarkers, contributing to the ongoing efforts in disease biomarker discovery.


Assuntos
Biomarcadores , Metaboloma , Metabolômica , Metabolômica/métodos , Humanos , Biomarcadores/análise , Biomarcadores/metabolismo , Estereoisomerismo , Espectrometria de Massas/métodos , Aminoácidos/metabolismo , Animais , Hidroxiácidos/metabolismo , Hidroxiácidos/análise
4.
Food Chem ; 462: 140966, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39197244

RESUMO

Noni fruit has an unpleasant flavour but is highly bioactive. Therefore, it is necessary to clarify the effect of temperature regulation on quality of fermented noni fruit. In the present study, the formation of flavours, amino acid profiles, and iridoid glycosides during noni fruit fermentation at different temperatures were investigated. We initially found that different temperatures affected core microbial communities. The general evolutionary trends of Acetobacter and Gluconobacter were influenced by different temperatures. Furthermore, high temperature helped maintain low octanoic and hexanoic acids. Subsequently, we found that high temperature improved total amino acids and iridoid glycosides. The correlation network analysis revealed that bacterial communities impacted the quality (volatile flavours, amino acid profiles, and iridoid glycosides) of fermented noni fruit. Overall, altering the temperature induced variations in microbial communities and quality during the noni fruit fermentation process. These results are instrumental in the pursuit of quality control in natural fermentation processes.


Assuntos
Aminoácidos , Bactérias , Fermentação , Frutas , Glicosídeos Iridoides , Microbiota , Morinda , Temperatura , Frutas/química , Frutas/metabolismo , Frutas/microbiologia , Aminoácidos/metabolismo , Aminoácidos/análise , Bactérias/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Morinda/química , Morinda/metabolismo , Glicosídeos Iridoides/metabolismo , Glicosídeos Iridoides/análise , Glicosídeos Iridoides/química , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/química , Aromatizantes/metabolismo , Aromatizantes/química
5.
Front Cell Infect Microbiol ; 14: 1436477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39355267

RESUMO

Aims: Hyperglycemia is one of the adverse effects of tacrolimus (TAC), but the underlying mechanism is not fully identified. We used multi-omics analysis to evaluate the changes in the gut microbiota and metabolic profile of rats with TAC-induced diabetes. Methods: To establish a diabetic animal model, Sprague Dawley rats were divided randomly into two groups. Those in the TAC group received intraperitoneal injections of TAC (3 mg/kg) for 8 weeks, and those in the CON group served as the control. 16S rRNA sequencing was used to analyze fecal microbiota. The metabolites of the two groups were detected and analyzed by nontargeted and targeted metabolomics, including amino acids (AAs), bile acids (BAs), and short-chain fatty acids (SCFAs). Results: The rats treated with TAC exhibited hyperglycemia as well as changes in the gut microbiota and metabolites. Specifically, their gut microbiota had significantly higher abundances of Escherichia-Shigella, Enterococcus, and Allobaculum, and significantly lower abundances of Ruminococcus, Akkermansia, and Roseburia. In addition, they had significantly reduced serum levels of AAs including asparagine, aspartic acid, glutamic acid, and methionine. With respect to BAs, they had significantly higher serum levels of taurocholic acid (TCA), and glycochenodeoxycholic acid (GCDCA), but significantly lower levels of taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA). There were no differences in the levels of SCFAs between the two groups. Correlations existed among glucose metabolism indexes (fasting blood glucose and fasting insulin), gut microbiota (Ruminococcus and Akkermansia), and metabolites (glutamic acid, hydroxyproline, GCDCA, TDCA, and TUDCA). Conclusions: Both AAs and BAs may play crucial roles as signaling molecules in the regulation of TAC-induced diabetes.


Assuntos
Aminoácidos , Fezes , Microbioma Gastrointestinal , Metabolômica , RNA Ribossômico 16S , Ratos Sprague-Dawley , Tacrolimo , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Tacrolimo/farmacologia , Ratos , Masculino , Fezes/microbiologia , RNA Ribossômico 16S/genética , Aminoácidos/metabolismo , Aminoácidos/sangue , Diabetes Mellitus Experimental/metabolismo , Ácidos e Sais Biliares/metabolismo , Ácidos Graxos Voláteis/metabolismo , Metaboloma/efeitos dos fármacos , Modelos Animais de Doenças , Hiperglicemia/metabolismo , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Bactérias/genética , Glicemia/metabolismo , Imunossupressores
6.
Yakugaku Zasshi ; 144(10): 911-918, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-39358246

RESUMO

π-Extended donor-acceptor (D-A)-type molecules, which bear both electron-donor and electron-acceptor substituents on the backbone, exhibit unique optical properties, such as bathochromic shifts in absorption and emission, large Stokes shifts, solvatochromic behavior, and fluorescence quenching in polar solvents. These unique properties are attributed to intramolecular charge transfer (ICT) or twisted intramolecular charge transfer (TICT) in the ground and excited states. This review article introduces three types of D-A-type molecules that are used as detection reagents for (1) methanol, (2) amino acids during solid-phase peptide synthesis (SPPS), and (3) amines present in the biological environment. For methanol detection, D-A-type fluorophores with basic guanidine moieties were developed to differentiate between methanol (MeOH) and ethanol (EtOH) based on the small difference in their pKa values (ΔpKa=0.4). Selective protonation of the guanidine moiety in methanol disrupts the D-A structure, allowing emission in the resultant polar environment. Similarly, an acid-base reaction between the hydrogen chloride (HCl) salts of the D-A-type molecules and amines is applied to detect amines during SPPS. In this method, a colorless solution of an HCl salt of the D-A-type molecule is deprotonated by amines, forming a yellow solution. This is the first reported quantitative and non-destructive colorimetric method for detecting amines. Finally, a turn-on-type amine-labeling reagent was developed for the nucleophilic aromatic substitution (SNAr) reaction. This new reagent enables protein staining of living cells with a large Stokes shift and without solvent-polarity-dependent fluorescence quenching.


Assuntos
Aminas , Aminoácidos , Metanol , Aminoácidos/análise , Aminas/química , Técnicas de Síntese em Fase Sólida , Peptídeos , Corantes Fluorescentes , Indicadores e Reagentes , Guanidina/química , Etanol/análise
7.
Arch Microbiol ; 206(11): 425, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361131

RESUMO

In the fields of cultured meat, biopharmaceuticals, cell therapy, and tissue engineering, large numbers of mammalian cells are required; thus, highly-concentrated cell cultures are widely adopted. In general, such cultures can lead to cell damage caused by waste product accumulation and nutritional inadequacy. In this study, a novel co-culture system where the recombinant lactate-assimilating cyanobacterial strain, KC0110, derived from euryhaline Picosynechococcus sp. PCC 7002, and mammalian muscle cells cultured across porous membranes been developed. By using the KC0110 strain, the amount of ammonium and lactate excreted from C2C12 mouse muscle cells into the culture significantly decreased. Importantly, pyruvate and some amino acids, including pyruvate-derived amino acids, also increased significantly compared to those in monoculture of C2C12 cells. It is believed that the organic acids secreted by the KC0110 strain enhance the growth of mammalian cells, leading to a reduction in high-concentration culture-induced mammalian cell damage [lactate dehydrogenase (LDH) release] through cyanobacterial co-culture. These results show that, through co-cultivation with cyanobacteria, it is possible to culture mammalian cells, alleviating cell damage, even in highly-concentrated cultures. This study demonstrated an in vitro "symbiotic circular system" that can interchange metabolites produced by phototrophs and mammalian cells.


Assuntos
Técnicas de Cocultura , Cianobactérias , Ácido Láctico , Animais , Camundongos , Ácido Láctico/metabolismo , Cianobactérias/metabolismo , Linhagem Celular , L-Lactato Desidrogenase/metabolismo , Ácido Pirúvico/metabolismo , Compostos de Amônio/metabolismo , Aminoácidos/metabolismo
8.
J Biochem Mol Toxicol ; 38(9): e23837, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39230010

RESUMO

Synthesis of novel unnatural amino acids (UAAs) from 4-oxo-4-phenylbut-2-enoic acid derivatives with intramolecular aza-Michael addition reaction in the presence of chlorosulfonyl isocyanate (CSI) was reported in soft conditions without any metal catalyst. Acids and base as a catalyst, and solvents effects were investigated for the synthesis of novel UAAs. This novel method provides inexpensive, practicable, and efficient approach to generate UAAs. The use of UAAs has attracted great interest in the development of therapeutic agents and drug discovery to improve their properties. In this context, in addition to the synthesis of new UAAs, their inhibition effects on important metabolic enzymes of acetylcholinesterase (AChE) and carbonic anhydrases I and II (hCA I and II) enzymes were investigated. The compound 2g showed the best inhibition for CA I and AChE enzymes, while compound 2i exhibited the best inhibition profile against CA II isoenzyme. The inhibition values of these compounds were found as 1.85 ± 0.64 for AChE, 0.53 ± 0.07 for hCA I, 0.44 ± 0.15 µM for hCA II, respectively, and they showed a stronger inhibitory property than acetazolamide (standard inhibitor for hCA I and II) and tacrine (standard inhibitor for AChE) molecules. The activity of the studied molecule against different proteins that are hCA I (PDB ID: 2CAB), hCA II (PDB ID: 5AML), and AChE (PDB ID: 1OCE) was examined. Finally, the drug properties of the studied molecule were examined by performing absorption, distribution, metabolism, excretion, and toxicity analysis.


Assuntos
Acetilcolinesterase , Aminoácidos , Anidrase Carbônica II , Anidrase Carbônica I , Inibidores da Anidrase Carbônica , Inibidores da Colinesterase , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacologia , Anidrase Carbônica I/antagonistas & inibidores , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Aminoácidos/química , Aminoácidos/síntese química , Anidrase Carbônica II/antagonistas & inibidores , Humanos , Proteínas de Transporte , Proteínas do Tecido Nervoso , Proteínas Ligadas por GPI
9.
Methods Enzymol ; 703: 121-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39260993

RESUMO

Thiol dioxygenases (TDOs) are non­heme Fe(II)­dependent enzymes that catalyze the O2-dependent oxidation of thiol substrates to their corresponding sulfinic acids. Six classes of TDOs have thus far been identified and two, cysteine dioxygenase (CDO) and cysteamine dioxygenase (ADO), are found in eukaryotes. All TDOs belong to the cupin superfamily of enzymes, which share a common ß­barrel fold and two cupin motifs: G(X)5HXH(X)3-6E(X)6G and G(X)5-7PXG(X)2H(X)3N. Crystal structures of TDOs revealed that these enzymes contain a relatively rare, neutral 3­His iron­binding facial triad. Despite this shared metal-binding site, TDOs vary greatly in their secondary coordination spheres. Site­directed mutagenesis has been used extensively to explore the impact of changes in secondary sphere residues on substrate specificity and enzymatic efficiency. This chapter summarizes site-directed mutagenesis studies of eukaryotic TDOs, focusing on the tools and practicality of non­standard amino acid incorporation.


Assuntos
Aminoácidos , Dioxigenases , Mutagênese Sítio-Dirigida , Dioxigenases/química , Dioxigenases/metabolismo , Dioxigenases/genética , Aminoácidos/metabolismo , Aminoácidos/química , Especificidade por Substrato , Cisteína Dioxigenase/química , Cisteína Dioxigenase/metabolismo , Cisteína Dioxigenase/genética , Compostos de Sulfidrila/metabolismo , Compostos de Sulfidrila/química , Humanos , Animais , Modelos Moleculares
10.
Sci Rep ; 14(1): 20987, 2024 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251672

RESUMO

Primary Hyperparathyroidism (PHPT) is characterized by excessive parathormone (PTH) secretion and disrupted calcium homeostasis. Untargeted metabolomics offers a valuable approach to understanding the complex metabolic alterations associated with different diseases, including PHPT. Plasma untargeted metabolomics was applied to investigate the metabolic profiles of PHPT patients compared to a control group. Two complementary liquid-phase separation techniques were employed to comprehensively explore the metabolic landscape in this retrospective, single-center study. The study comprised 28 female patients diagnosed following the current guidelines of PHPT diagnosis and a group of 30 healthy females as a control group. To evaluate their association with PHPT, we identified changes in plasma metabolic profiles in patients with PHPT compared to the control group. The primary outcome measure included detecting plasma metabolites and discriminating PHPT patients from controls. The study unveiled specific metabolic imbalances that may link L-amino acids with peptic ulcer disease, gamma-glutamyls with oxidative stress, and asymmetric dimethylarginine (ADMA) with cardiovascular complications. Several metabolites, such as gamma-glutamyls, caffeine, sex hormones, carnitine, sphingosine-1-phosphate (S-1-P), and steroids, were connected with reduced bone mineral density (BMD). Metabolic profiling identified distinct metabolic patterns between patients with PHPT and healthy controls. These findings provided valuable insights into the pathophysiology of PHPT.


Assuntos
Hiperparatireoidismo Primário , Metabolômica , Humanos , Feminino , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/metabolismo , Metabolômica/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Metaboloma , Arginina/sangue , Arginina/metabolismo , Arginina/análogos & derivados , Densidade Óssea , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/metabolismo , Estudos de Casos e Controles , Adulto , Aminoácidos/sangue , Aminoácidos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/sangue , Esfingosina/metabolismo , Lisofosfolipídeos/sangue , Lisofosfolipídeos/metabolismo , Biomarcadores/sangue
11.
Chem Pharm Bull (Tokyo) ; 72(9): 804-809, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39261085

RESUMO

Protein-based enzymes are among the most efficient catalysts on our planet. A common feature of protein enzymes is that all catalytic amino acids occupy a limited, narrow space and face each other. In this study, we created a theoretical novel biomimetic molecule containing different multiple catalytic peptides. Although single peptides are far less catalytically efficient than protein enzymes, Octopus-arms-mimicking biomolecules containing eight different peptides (Octopuzymes) can efficiently catalyze organic reactions. Since structural information for extant protein enzymes, predicted enzymes based on genome data, and artificially designed enzymes is available for designing Octopuzymes, they could in theory mimic all protein enzyme reactions on our planet. Moreover, besides L-amino acids, peptides can contain D-amino acids, non-natural amino acids, chemically modified amino acids, nucleotides, vitamins, and manmade catalysts, leading to a huge expansion of catalytic space compared with extant protein enzymes. Once a reaction catalyzed by an Octopuzyme is defined, it could be rapidly evolvable via multiple amino acid substitutions on the eight peptides of Octopuzymes.


Assuntos
Peptídeos , Peptídeos/química , Catálise , Aminoácidos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo
12.
Bioorg Med Chem ; 112: 117900, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39217687

RESUMO

The incorporation of non-canonical amino acids (ncAAs) into the metal coordination environments of proteins has endowed metalloproteins with enhanced properties and novel activities, particularly in hemoproteins. In this work, we disclose a scalable synthetic strategy that enables the production of myoglobin (Mb) variants with non-canonical heme ligands, i.e., HoCys and f4Tyr. The ncAA-containing Mb* variants (with H64V/V68A mutations) were obtained through two consecutive native chemical ligations and a subsequent desulfurization step, with overall isolated yield up to 28.6 % in over 10-milligram scales. After refolding and heme b cofactor reconstitution, the synthetic Mb* variants showed typical electronic absorption bands. When subjected to the catalysis of the cyclopropanation of styrene, both synthetic variants, however, were not as competent as the His-ligated Mb*. We envisioned that the synthetic method reported herein would be useful for incorporating a variety of ncAAs with diverse structures and properties into Mb for varied purposes.


Assuntos
Heme , Mioglobina , Mioglobina/química , Mioglobina/metabolismo , Ligantes , Heme/química , Heme/metabolismo , Estrutura Molecular , Aminoácidos/química , Aminoácidos/metabolismo
13.
Nat Commun ; 15(1): 7531, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237489

RESUMO

Binding-activated optical sensors are powerful tools for imaging, diagnostics, and biomolecular sensing. However, biosensor discovery is slow and requires tedious steps in rational design, screening, and characterization. Here we report on a platform that streamlines biosensor discovery and unlocks directed nanosensor evolution through genetically encodable fluorogenic amino acids (FgAAs). Building on the classical knowledge-based semisynthetic approach, we engineer ~15 kDa nanosensors that recognize specific proteins, peptides, and small molecules with up to 100-fold fluorescence increases and subsecond kinetics, allowing real-time and wash-free target sensing and live-cell bioimaging. An optimized genetic code expansion chemistry with FgAAs further enables rapid (~3 h) ribosomal nanosensor discovery via the cell-free translation of hundreds of candidates in parallel and directed nanosensor evolution with improved variant-specific sensitivities (up to ~250-fold) for SARS-CoV-2 antigens. Altogether, this platform could accelerate the discovery of fluorogenic nanosensors and pave the way to modify proteins with other non-standard functionalities for diverse applications.


Assuntos
Aminoácidos , Técnicas Biossensoriais , Corantes Fluorescentes , SARS-CoV-2 , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Humanos , SARS-CoV-2/genética , COVID-19/virologia , Nanotecnologia/métodos , Peptídeos/metabolismo , Peptídeos/química , Peptídeos/genética
14.
Sci Rep ; 14(1): 20680, 2024 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237693

RESUMO

Gliomas are highly complex and metabolically active brain tumors associated with poor prognosis. Recent reports have found altered levels of blood metabolites during early tumor development, suggesting that tumor development could be detected several years before clinical manifestation. In this study, we performed metabolite analyses of blood samples collected from healthy controls and future glioma patients, up to eight years before glioma diagnosis, and on the day of glioma surgery. We discovered that metabolites related to early glioma development were associated with an increased energy turnover, as highlighted by elevated levels of TCA-related metabolites such as fumarate, malate, lactate and pyruvate in pre-diagnostic cases. We also found that metabolites related to glioma progression at surgery were primarily high levels of amino acids and metabolites of amino acid catabolism, with elevated levels of 11 amino acids and two branched-chain alpha-ketoacids, ketoleucine and ketoisoleucine. High amino acid turnover in glioma tumor tissue is currently utilized for PET imaging, diagnosis and delineation of tumor margins. By examining blood-based metabolic progression patterns towards disease onset, we demonstrate that this high amino acid turnover is also detectable in a simple blood sample. These findings provide additional insight of metabolic alterations during glioma development and progression.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Glioma , Humanos , Glioma/sangue , Glioma/cirurgia , Glioma/diagnóstico , Glioma/patologia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/metabolismo , Masculino , Feminino , Biomarcadores Tumorais/sangue , Pessoa de Meia-Idade , Adulto , Progressão da Doença , Aminoácidos/sangue , Aminoácidos/metabolismo
15.
Nat Commun ; 15(1): 7980, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266567

RESUMO

Modern life is essentially homochiral, containing D-sugars in nucleic acid backbones and L-amino acids in proteins. Since coded proteins are theorized to have developed from a prebiotic RNA World, the homochirality of L-amino acids observed in all known life presumably resulted from chiral transfer from a homochiral D-RNA World. This transfer would have been mediated by aminoacyl-RNAs defining the genetic code. Previous work on aminoacyl transfer using tRNA mimics has suggested that aminoacylation using D-RNA may be inherently biased toward reactivity with L-amino acids, implying a deterministic path from a D-RNA World to L-proteins. Using a model system of self-aminoacylating D-ribozymes and epimerizable activated amino acid analogs, we test the chiral selectivity of 15 ribozymes derived from an exhaustive search of sequence space. All of the ribozymes exhibit detectable selectivity, and a substantial fraction react preferentially to produce the D-enantiomer of the product. Furthermore, chiral preference is conserved within sequence families. These results are consistent with the transfer of chiral information from RNA to proteins but do not support an intrinsic bias of D-RNA for L-amino acids. Different aminoacylation structures result in different directions of chiral selectivity, such that L-proteins need not emerge from a D-RNA World.


Assuntos
Aminoácidos , Aminoacilação , RNA Catalítico , RNA Catalítico/metabolismo , RNA Catalítico/química , RNA Catalítico/genética , Aminoácidos/química , Aminoácidos/metabolismo , Estereoisomerismo , Conformação de Ácido Nucleico , RNA/metabolismo , RNA/genética , RNA/química , Código Genético
16.
Plant Physiol Biochem ; 215: 109084, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39217823

RESUMO

Amino acids serve as the primary means of transport and organic nitrogen carrier in plants, playing an essential role in plant growth and development. Amino acid transporters (AATs) facilitate the movement of amino acids within plants and have been identified and characterised in a number of species. It has been demonstrated that these amino acid transporters exert an influence on the quality attributes of plants, in addition to their primary function of transporting amino acid transport. This paper presents a summary of the role of AATs in plant quality improvement. This encompasses the enhancement of nitrogen utilization efficiency, root development, tiller number and fruit yield. Concurrently, AATs can bolster the resilience of plants to pests, diseases and abiotic stresses, thereby further enhancing the yield and quality of fruit. AATs exhibit a wide range of substrate specificity, which greatly optimizes the use of pesticides and significantly reduces pesticide residues, and reduces the risk of environmental pollution while increasing the safety of fruit. The discovery of AATs function provides new ideas and ways to cultivate high-quality crop and promote changes in agricultural development, and has great potential in the application of plant quality improvement.


Assuntos
Sistemas de Transporte de Aminoácidos , Sistemas de Transporte de Aminoácidos/metabolismo , Proteínas de Plantas/metabolismo , Produtos Agrícolas/metabolismo , Aminoácidos/metabolismo , Plantas/metabolismo
17.
Sci Rep ; 14(1): 21055, 2024 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-39251658

RESUMO

Nutritional status assessment, including amino acids, carnitine, and acylcarnitine profile, is an important component of diabetes care management, influencing growth and metabolic regulation. A designed case-control research included 100 Egyptian participants (50 T1DM and 50 healthy controls) aged 6 to 18 years old. The participants' nutritional status was assessed using the Body Mass Index (BMI) Z-score. Extended metabolic screening (EMS) was performed using a high-performance liquid chromatography-electrospray ionization-mass spectroscopy system to evaluate the levels of 14 amino acids, free carnitine, and 27 carnitine esters. T1DM children had considerably lower anthropometric Z-scores than the control group, with 16% undernutrition and 32% short stature. Total aromatic amino acids, phenylalanine, phenylalanine/tyrosine ratio, proline, arginine, leucine, isoleucine, free carnitine, and carnitine esters levels were considerably lower in the diabetic group, suggesting an altered amino acid and carnitine metabolism in type 1 diabetes. BMI Z-score showed a significant positive correlation with Leucine, Isoleucine, Phenylalanine, Citrulline, Tyrosine, Arginine, Proline, free carnitine, and some carnitine esters (Acetylcarnitine, Hydroxy-Isovalerylcarnitine, Hexanoylcarnitine, Methylglutarylcarnitine, Dodecanoylcarnitine, Tetradecanoylcarnitine, and Hexadecanoylcarnitine). HbA1c% had a significant negative correlation with Total aromatic amino acids, Branched-chain amino acid/Total aromatic amino acids ratio, Glutamic Acid, Citrulline, Tyrosine, Arginine, Proline, and certain carnitine esters (Propionylcarnitine, Methylglutarylcarnitine, Decanoylcarnitine, Octadecanoylcarnitine and Octadecenoylcarnitine), suggest that dysregulated amino acid and carnitine metabolism may be negatively affect the glycaemic control in children with TIDM. In conclusion, regular nutritional assessments including EMS of T1DM patients are critical in terms of diet quality and protein content for improved growth and glycemic management.


Assuntos
Aminoácidos , Carnitina , Diabetes Mellitus Tipo 1 , Estado Nutricional , Humanos , Criança , Masculino , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Adolescente , Egito , Carnitina/análogos & derivados , Carnitina/metabolismo , Carnitina/sangue , Estudos de Casos e Controles , Aminoácidos/metabolismo , Índice de Massa Corporal
18.
Chem Pharm Bull (Tokyo) ; 72(9): 817-825, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39313386

RESUMO

The triboelectric properties of active pharmaceutical ingredients (APIs) contribute to problems during the manufacturing of pharmaceuticals. However, the triboelectric properties of APIs have not been comprehensively characterized. In this study, the effect of salt formulation on the triboelectric properties of APIs was investigated. The triboelectric properties of three groups of amines, namely tertiary amines, purine bases, and amino acids, and their hydrochlorides were evaluated using a suction-type Faraday cage meter. Most of the hydrochloride salts exhibited more negative charges than the corresponding free bases, and the degree by which the triboelectric property changed upon hydrochlorination depended on the structural groups of the compounds. In the case of tertiary amines, the change in the zero-charge margin upon hydrochlorination was negatively correlated with the zero-charge margin of the free base. In contrast, hydrochlorination of the amino acids led to a significant change in the zero-charge margin. In most cases, salt formation also affected the triboelectric properties of API powders. Controlling the triboelectric properties of APIs solves various problems caused by the electrification of raw material powders and granules during the production of pharmaceuticals, thereby increasing the quality of produced pharmaceuticals.


Assuntos
Aminas , Sais , Aminas/química , Sais/química , Preparações Farmacêuticas/química , Aminoácidos/química , Princípios Ativos
19.
J Mass Spectrom ; 59(10): e5089, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39302082

RESUMO

A peptide's fractional mass is directly associated with its elemental composition and thus amino acid composition. Here it is demonstrated that a peptide's fractional mass alone can be a useful identifier or indicator of that composition for small to mid-sized peptides (5-7 amino acids) and can significantly reduce the number of viable amino acid compositions for larger peptides (> 8 residues) to include or exclude certain possibilities. Separate consideration of the integer portion of the peptide's mass helps to reduce the number of possibilities where many duplicate fractional mass values are found. Adoption of this fractional mass strategy should aid approaches that are presently employed for peptide identification, including in the use of mass map data to search protein databases for proteomics applications.


Assuntos
Aminoácidos , Peptídeos , Proteômica , Aminoácidos/análise , Aminoácidos/química , Peptídeos/análise , Peptídeos/química , Proteômica/métodos , Bases de Dados de Proteínas , Peso Molecular , Espectrometria de Massas/métodos , Sequência de Aminoácidos
20.
Chemosphere ; 364: 143252, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39236918

RESUMO

Ionic liquids (ILs) have found diverse applications in research and industry. Biocompatible ILs, a subset considered less toxic than traditional ILs, have expanded their applications into biomedical fields. However, there is limited understanding of the toxicity profiles, safe concentrations, and underlying factors driving their toxicity. In this study, we investigated the cytotoxicity of 13 choline-based ILs using four different cell lines: Human dermal fibroblasts (HDF), epidermoid carcinoma cells (A431), cervical cancer cells (HeLa), and gastric cancer cells (AGS). Additionally, we explored the haemolytic activity of these ILs. Our findings showed that the cytotoxic and haemolytic activities of ILs can be attributed to the hydrophobicity of the anions and the pH of the IL solutions. Furthermore, utilising quartz crystal microbalance with dissipation (QCM-D), we delved into the interaction of selected ILs, including choline acetate [Cho][Ac] and choline geranate [Cho][Ge], with model cell membranes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The QCM-D data showed that ILs with higher toxicities exhibited more pronounced interactions with membranes. Increased variations in frequency and dissipation reflected substantial changes in membrane fluidity and mass following the addition of the more toxic ILs. Furthermore, total internal reflection fluorescence microscopy study revealed that [Cho][Ac] could cause lipid rearrangements and pore formation in the membrane, while [Cho][Ge] disrupted the bilayer packing. This study advances our understanding of the cellular toxicities associated with choline-based ILs and provides valuable insights into their mechanisms of action concerning IL-membrane interactions. These findings have significant implications for the safe and informed utilisation of biocompatible ILs in the realm of drug delivery and biotechnology.


Assuntos
Acetatos , Aminoácidos , Ânions , Membrana Celular , Colina , Líquidos Iônicos , Líquidos Iônicos/química , Líquidos Iônicos/toxicidade , Humanos , Colina/química , Ânions/química , Membrana Celular/efeitos dos fármacos , Acetatos/química , Acetatos/toxicidade , Aminoácidos/química , Interações Hidrofóbicas e Hidrofílicas , Células HeLa , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos
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