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1.
BMC Bioinformatics ; 21(1): 340, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738892

RESUMO

BACKGROUND: Ribosome profiling has been widely used for studies of translation under a large variety of cellular and physiological contexts. Many of these studies have greatly benefitted from a series of data-mining tools designed for dissection of the translatome from different aspects. However, as the studies of translation advance quickly, the current toolbox still falls in short, and more specialized tools are in urgent need for deeper and more efficient mining of the important and new features of the translation landscapes. RESULTS: Here, we present RiboMiner, a bioinformatics toolset for mining of multi-dimensional features of the translatome with ribosome profiling data. RiboMiner performs extensive quality assessment of the data and integrates a spectrum of tools for various metagene analyses of the ribosome footprints and for detailed analyses of multiple features related to translation regulation. Visualizations of all the results are available. Many of these analyses have not been provided by previous methods. RiboMiner is highly flexible, as the pipeline could be easily adapted and customized for different scopes and targets of the studies. CONCLUSIONS: Applications of RiboMiner on two published datasets did not only reproduced the main results reported before, but also generated novel insights into the translation regulation processes. Therefore, being complementary to the current tools, RiboMiner could be a valuable resource for dissections of the translation landscapes and the translation regulations by mining the ribosome profiling data more comprehensively and with higher resolution. RiboMiner is freely available at https://github.com/xryanglab/RiboMiner and https://pypi.org/project/RiboMiner .


Assuntos
Biologia Computacional/métodos , Biossíntese de Proteínas , Ribossomos/metabolismo , Software , Motivos de Aminoácidos , Sequência de Aminoácidos , Aminoácidos/genética , Códon/genética , Análise de Dados , Mineração de Dados
2.
Oecologia ; 193(4): 827-842, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32857190

RESUMO

Hydrogen isotope (δ2H) analysis has been routinely used as an ecological tracer for animal movement and migration, yet a biochemical understanding of how animals incorporate this element in the synthesis of tissues is poorly resolved. Here, we apply a new analytical tool, amino acid (AA) δ2H analysis, in a controlled setting to trace the influence of drinking water and dietary macromolecules on the hydrogen in muscle tissue. We varied the δ2H of drinking water and the proportions of dietary protein and carbohydrates with distinct hydrogen and carbon isotope compositions fed to house mice among nine treatments. Our results show that hydrogen in the non-essential (AANESS) and essential (AAESS) AAs of mouse muscle is not readily exchanged with body water, but rather patterns among these compounds can be described through consideration of the major biochemical pathway(s) used by organisms to synthesize or route them from available sources. Dietary carbohydrates contributed more hydrogen than drinking water to the synthesis of AANESS in muscle. While neither drinking water nor dietary carbohydrates directly contributed to muscle AAESS, we did find that a minor but measurable proportion (10-30%) of the AAESS in muscle was synthesized by the gut microbiome using hydrogen and carbon from dietary carbohydrates. δ2H patterns among individual AAs in mice muscle are similar to those we previously reported for bacteria, which provides additional support that this approach may allow for the simultaneous analysis of different AAs that are more influenced by drinking water (AANESS) versus dietary (AAESS) sources of hydrogen.


Assuntos
Aminoácidos , Água , Animais , Isótopos de Carbono , Proteínas na Dieta , Hidrogênio , Camundongos , Isótopos de Nitrogênio
3.
J Med Life ; 13(2): 241-248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742521

RESUMO

Cell culture is one of the most commonly used techniques in the production of biological products. Many physical and chemical parameters may affect cell growth and proliferation. This study was conducted to investigate the effect of chemical components as supplements using the experimental design method, which aimed at reducing the number of experiments. For this purpose, supplements including chemical components using four levels, with three replications in suspension and batch culture conditions, were examined for 72 hours using the Taguchi experimental design method. From the experiments, it was concluded that the culture media composition had a significant impact on final cell count and pH. High concentrations of different media composition alone were insufficient to ensure higher cell count. According to the results, this insufficiency was associated with an increase of 20% in the number of final cells. In the majority of cultures, the number of final cells at 48 hours increased relative to the number of final cells at 24 hours after culturing the cells.


Assuntos
Técnicas de Cultura de Células/métodos , Vírus da Febre Aftosa/imunologia , Rim/citologia , Vacinas Virais/imunologia , Aminoácidos/farmacologia , Animais , Contagem de Células , Células Cultivadas , Cricetinae , Vírus da Febre Aftosa/efeitos dos fármacos , Glucose/farmacologia , Concentração de Íons de Hidrogênio , Polietilenoglicóis/química , Proteínas/farmacologia , Vitaminas/farmacologia
4.
Nat Commun ; 11(1): 3818, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732937

RESUMO

The formation of peptide bonds by energetic processing of amino acids is an important step towards the formation of biologically relevant molecules. As amino acids are present in space, scenarios have been developed to identify the roots of life on Earth, either by processes occurring in outer space or on Earth itself. We study the formation of peptide bonds in single collisions of low-energy He2+ ions (α-particles) with loosely bound clusters of ß-alanine molecules at impact energies typical for solar wind. Experimental fragmentation mass spectra produced by collisions are compared with results of molecular dynamics simulations and an exhaustive exploration of potential energy surfaces. We show that peptide bonds are efficiently formed by water molecule emission, leading to the formation of up to tetrapeptide. The present results show that a plausible route to polypeptides formation in space is the collision of energetic ions with small clusters of amino acids.


Assuntos
Aminoácidos/química , Simulação de Dinâmica Molecular , Peptídeos/química , Termodinâmica , beta-Alanina/química , Dipeptídeos/síntese química , Dipeptídeos/química , Íons/química , Oligopeptídeos/síntese química , Oligopeptídeos/química , Peptídeos/síntese química , Espectrometria de Massas por Ionização por Electrospray/métodos , Água/química
5.
Adv Exp Med Biol ; 1265: 1-20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761567

RESUMO

Dietary protein digestion is an efficient process resulting in the absorption of amino acids by epithelial cells, mainly in the jejunum. Some amino acids are extensively metabolized in enterocytes supporting their high energy demand and/or production of bioactive metabolites such as glutathione or nitric oxide. In contrast, other amino acids are mainly used as building blocks for the intense protein synthesis associated with the rapid epithelium renewal and mucin production. Several amino acids have been shown to support the intestinal barrier function and the intestinal endocrine function. In addition, amino acids are metabolized by the gut microbiota that use them for their own protein synthesis and in catabolic pathways releasing in the intestinal lumen numerous metabolites such as ammonia, hydrogen sulfide, branched-chain amino acids, polyamines, phenolic and indolic compounds. Some of them (e.g. hydrogen sulfide) disrupts epithelial energy metabolism and may participate in mucosal inflammation when present in excess, while others (e.g. indole derivatives) prevent gut barrier dysfunction or regulate enteroendocrine functions. Lastly, some recent data suggest that dietary amino acids might regulate the composition of the gut microbiota, but the relevance for the intestinal health remains to be determined. In summary, amino acid utilization by epithelial cells or by intestinal bacteria appears to play a pivotal regulator role for intestinal homeostasis. Thus, adequate dietary supply of amino acids represents a key determinant of gut health and functions.


Assuntos
Aminoácidos/metabolismo , Saúde , Intestinos/fisiologia , Proteínas na Dieta/metabolismo , Microbioma Gastrointestinal , Humanos
6.
Adv Exp Med Biol ; 1265: 21-37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761568

RESUMO

The liver plays a central role in amino acid (AA) metabolism in humans and other animals. In all mammals, this organ synthesizes many AAs (including glutamate, glutamine, alanine, aspartate, asparagine, glycine, serine, and homoarginine), glucose, and glutathione (a major antioxidant). Similar biochemical reactions occur in the liver of birds except for those for arginine and glutamine hydrolysis, proline oxidation, and gluconeogenesis from AAs. In contrast to mammals and birds, the liver of fish has high rates of glutamate and glutamine oxidation for ATP production. In most animals (except for cats and possibly some of the other carnivores), the liver produces taurine from methionine or cysteine. However, the activity of this pathway is limited in human infants (particularly preterm infants) and is also low in adult humans as compared with rats, birds and livestock species (e.g., pigs, cattle and sheep). The liver exhibits metabolic zonation and intracellular compartmentation for ureagenesis, uric acid synthesis, and gluconeogenesis, as well as AA degradation and syntheses. Capitalizing on these extensive bases of knowledge, dietary supplementation with functional AAs (e.g., methionine, N-acetylcysteine, and glycine) to humans and other animals can alleviate or prevent oxidative stress and damage in the liver. Because liver diseases are common problems in humans and farm animals (including fish), much research is warranted to further both basic and applied research on hepatic AA metabolism and functions.


Assuntos
Aminoácidos/metabolismo , Fígado/metabolismo , Animais , Humanos
7.
Adv Exp Med Biol ; 1265: 39-56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761569

RESUMO

Cardiovascular disease is the major cause of global mortality and disability. Abundant evidence indicates that amino acids play a fundamental role in cardiovascular physiology and pathology. Decades of research established the importance of L-arginine in promoting vascular health through the generation of the gas nitric oxide. More recently, L-glutamine, L-tryptophan, and L-cysteine have also been shown to modulate vascular function via the formation of a myriad of metabolites, including a number of gases (ammonia, carbon monoxide, hydrogen sulfide, and sulfur dioxide). These amino acids and their metabolites preserve vascular homeostasis by regulating critical cellular processes including proliferation, migration, differentiation, apoptosis, contractility, and senescence. Furthermore, they exert potent anti-inflammatory and antioxidant effects in the circulation, and block the accumulation of lipids within the arterial wall. They also mitigate known risk factors for cardiovascular disease, including hypertension, hyperlipidemia, obesity, and diabetes. However, in some instances, the metabolism of these amino acids through discrete pathways yields compounds that fosters vascular disease. While supplementation with amino acid monotherapy targeting the deficiency has ameliorated arterial disease in many animal models, this approach has been less successful in the clinic. A more robust approach combining amino acid supplementation with antioxidants, anti-inflammatory agents, and/or specific amino acid enzymatic pathway inhibitors may prove more successful. Alternatively, supplementation with amino acid-derived metabolites rather than the parent molecule may elicit beneficial effects while bypassing potentially harmful pathways of metabolism. Finally, there is an emerging recognition that circulating levels of multiple amino acids are perturbed in vascular disease and that a more holistic approach that targets all these amino acid derangements is required to restore circulatory function in diseased blood vessels.


Assuntos
Aminoácidos/metabolismo , Sistema Cardiovascular/metabolismo , Saúde , Animais , Doenças Cardiovasculares/metabolismo , Endotélio Vascular/metabolismo , Humanos , Doenças Metabólicas/metabolismo , Óxido Nítrico/metabolismo
8.
Adv Exp Med Biol ; 1265: 57-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761570

RESUMO

Lung diseases affect millions of individuals all over the world. Various environmental factors, such as toxins, chemical pollutants, detergents, viruses, bacteria, microbial dysbiosis, and allergens, contribute to the development of respiratory disorders. Exposure to these factors activates stress responses in host cells and disrupt lung homeostasis, therefore leading to dysfunctional epithelial barriers. Despite significant advances in therapeutic treatments for lung diseases in the last two decades, novel interventional targets are imperative, considering the side effects and limited efficacy in patients treated with currently available drugs. Nutrients, such as amino acids (e.g., arginine, glutamine, glycine, proline, taurine, and tryptophan), peptides, and bioactive molecules, have attracted more and more attention due to their abilities to reduce oxidative stress, inhibit apoptosis, and regulate immune responses, thereby improving epithelial barriers. In this review, we summarize recent advances in amino acid metabolism in the lungs, as well as multifaceted functions of amino acids in attenuating inflammatory lung diseases based on data from studies with both human patients and animal models. The underlying mechanisms for the effects of physiological amino acids are likely complex and involve cell signaling, gene expression, and anti-oxidative reactions. The beneficial effects of amino acids are expected to improve the respiratory health and well-being of humans and other animals. Because viruses (e.g., coronavirus) and environmental pollutants (e.g., PM2.5 particles) induce severe damage to the lungs, it is important to determine whether dietary supplementation or intravenous administration of individual functional amino acids (e.g., arginine-HCl, citrulline, N-acetylcysteine, glutamine, glycine, proline and tryptophan) or their combinations to affected subjects may alleviate injury and dysfunction in this vital organ.


Assuntos
Aminoácidos/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Pneumopatias/metabolismo , Pneumopatias/patologia , Animais , Humanos , Pneumopatias/fisiopatologia
9.
Adv Exp Med Biol ; 1265: 71-95, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761571

RESUMO

The kidneys are developed from the intermediate mesoderm of the embryo. They are important for osmoregulation, regulation of acid-base balance, reabsorption of nutrients, and excretion of metabolites. In fish, the kidneys also serve as a hematopoietic, lymphoid and endocrine organ for the generation of red blood cells, the development of lymphocytes, and the production of hormones (e.g., glucocorticoids, catecholamines, and thyroid hormones). In humans and all animals, kidneys play a vital role in the metabolism and reabsorption of amino acids (AAs) and glucose. Specifically, this organ contributes to glucose synthesis from AAs, lactate and pyruvate via the gluconeogenesis pathway; regulates acid-base balance via inter-organ metabolism of glutamine; and synthesizes arginine, tyrosine, and glycine, respectively, from citrulline, phenylalanine, and 4-hydroxyproline. In mammals and birds, kidneys participate in creatine synthesis. Renal dysfunction adversely alters the concentrations of AAs in blood, while promoting muscle protein breakdown, inflammation, mitochondrial abnormalities, defects in the immune response, and cardiovascular diseases. Moderation of dietary AA intake has a protective and therapeutic effect on chronic kidney disease. Understanding the functions and metabolism of AAs in kidneys is essential for maintaining whole-body homeostasis, improving health and well-being, and preventing or treating renal metabolic diseases in humans and farm animals (including swine, poultry, ruminants, fish and shrimp).


Assuntos
Aminoácidos/metabolismo , Rim/metabolismo , Rim/fisiologia , Animais , Gluconeogênese , Glucose/biossíntese , Humanos
10.
Adv Exp Med Biol ; 1265: 97-109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761572

RESUMO

Dietary amino acids play an important role in maintaining health. Branched chain amino acids can adversely increase blood pressure whereas arginine and citrulline can reduce it. D-amino acids play important roles in several cell types including testis, the nervous system and adrenal glands. Several amino acids also can have dramatic effects on diabetes; branched chain amino acids, phenylalanine and tyrosine have been implicated while others, namely arginine and citrulline can improve outcomes. Leucine has been shown to play important roles in muscle primarily through the mTOR pathway though this effect does not translate across every population. Glutamine, arginine and D-aspartate also exert their muscle effects through mTOR. Relationships between amino acids and endocrine function include that of glucocorticoids, thyroid function, glucagon-like peptide 1 (GLP-1), ghrelin, insulin-like growth factor-1 (IGF-1) and leptin. Leucine, for example, can alleviate the effect of dexamethasone on muscle protein accretion. Interestingly, amino acid transporters play an important role in thyroid function. Several amino acids have been shown to increase GLP-1 levels in non-diabetics when administered orally. Similarly, several amino acids increase ghrelin levels in different species while cysteine can decrease it in mice. There is evidence to suggest that the arginine/NO pathway may be involved in modulating some of the effects of ghrelin on cells. In regard to IGF-1, branched chain amino acids can increase levels in adults while tryptophan and phenylalanine have been shown to increase levels in infants. Finally, leptin levels can be elevated by branched chain amino acids while restricting leucine in high fat diets can increase leptin sensitivity.


Assuntos
Aminoácidos/metabolismo , Sistema Endócrino/metabolismo , Animais , Grelina , Humanos
11.
Adv Exp Med Biol ; 1265: 111-131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761573

RESUMO

Amino acids are not only the building blocks of proteins, an indispensable component of cells, but also play versatile roles in regulating cell metabolism, proliferation, differentiation and growth by themselves or through their derivatives. At the whole body level, the bioavailability and metabolism of amino acids, interacting with other macronutrients, is critical for the physiological processes of reproduction including gametogenesis, fertilization, implantation, placentation, fetal growth and development. In fertilization and early pregnancy, histotroph in oviductal and uterine secretions provides nutrients and microenvironment for conceptus (embryo and extraembryonic membranes) development. These nutrients include select amino acids in histotroph (arginine, leucine and glutamine of particular interest) that stimulate conceptus growth and development, as well as interactions between maternal uterus and the conceptus, thus impacting maintenance of pregnancy, placental growth, development and functions, fetal growth and development, and consequential pregnancy outcomes. Gestational protein undernutrition causes fetal growth restriction and predisposes cardiovascular, metabolic diseases and others in offspring via multiple mechanisms, whereas the supplementation of glycine, leucine and taurine during pregnancy partially rescues growth restriction and beneficially modulates fetal programming. Thus, amino acids are essential for the fertility of humans and all animals.


Assuntos
Aminoácidos/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Reprodução/fisiologia , Animais , Implantação do Embrião , Feminino , Desenvolvimento Fetal , Humanos , Gravidez , Útero/metabolismo
12.
Adv Exp Med Biol ; 1265: 133-151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761574

RESUMO

The intestine interacts with a diverse community of antigens and bacteria. To keep its homeostasis, the gut has evolved with a complex defense system, including intestinal microbiota, epithelial layer and lamina propria. Various factors (e.g., nutrients) affect the intestinal defensive system and progression of intestinal diseases. This review highlights the current understanding about the role of amino acids (AAs) in protecting the intestine from harm. Amino acids (e.g., arginine, glutamine and tryptophan) are essential for the function of intestinal microbiota, epithelial cells, tight junction, goblet cells, Paneth cells and immune cells (e.g., macrophages, B cells and T cells). Through the modulation of the intestinal defensive system, AAs maintain the integrity and function of the intestinal mucosa and inhibit the progression of various intestinal diseases (e.g., intestinal infection and intestinal colitis). Thus, adequate intake of functional AAs is crucial for intestinal and whole-body health in humans and other animals.


Assuntos
Aminoácidos/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Animais , Colite , Microbioma Gastrointestinal , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Junções Íntimas
13.
Adv Exp Med Biol ; 1265: 167-185, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761576

RESUMO

Amino acids (AAs) and their metabolites play an important role in neurological health and function. They are not only the building blocks of protein but are also neurotransmitters. In the brain, glutamate and aspartate are the major excitatory neurotransmitters, whereas γ-aminobutyrate (GABA, a metabolite of glutamate) and glycine are the major inhibitory neurotransmitters. Nitric oxide (NO, a metabolite of arginine), H2S (a metabolite of cysteine), serotonin (a metabolite of tryptophan) and histamine (a metabolite of histidine), as well as dopamine and norepinephrine (metabolites of tyrosine) are neurotransmitters to modulate synaptic plasticity, neuronal activity, learning, motor control, motivational behavior, emotion, and executive function. Concentrations of glutamine (a precursor of glutamate and aspartate), branched-chain AAs (precursors of glutamate, glutamine and aspartate), L-serine (a precursor of glycine and D-serine), methionine and phenylalanine in plasma are capable of affecting neurotransmission through the syntheses of glutamate, aspartate, and glycine, as well as the competitive transport of tryptophan and tyrosine across from the blood-brain barrier. Adequate consumption of AAs is crucial to maintain their concentrations and the production of neurotransmitters in the central nervous system. Thus, the content and balance of AAs in diets have a profound impact on food intake by animals. Knowledge of AA transport and metabolism in the brain is beneficial for improving the health and well-being of humans and animals.


Assuntos
Aminoácidos/metabolismo , Encéfalo/metabolismo , Comportamento Alimentar/fisiologia , Animais , Humanos , Neurotransmissores/metabolismo
14.
Adv Exp Med Biol ; 1265: 187-199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761577

RESUMO

Amino acids are the building blocks of all proteins, including the most abundant fibrous proteins in the skin, as keratins, collagen and elastin. Sagging and wrinkled skin are features of chronic sun-damaged and aged uncared skin, and they are mainly associated with the deterioration of collagen and elastic fibers. The maintenance of skin structures by self-repair processes is essential to skin health. Thus, amino acids significantly impact the appearance of the skin. Amino acids are important nutrients required for (a) wound healing promotion and repair of the damaged skin; (b) acid-base balance and water retention in cellular layers, such as stratum corneum; (c) protection against sunlight damage; (d) maintenance of an appropriate skin microbiome. This review highlights the contribution of all proteinogenic amino acids and some related metabolites to the skin structures as constituents of the main cutaneous proteins or as signaling molecules for the regulation and determination of skin physiology.


Assuntos
Aminoácidos/metabolismo , Pele/metabolismo , Colágeno , Elastina , Humanos , Queratinas , Pele/citologia , Pele/microbiologia , Envelhecimento da Pele
15.
Adv Exp Med Biol ; 1265: 201-217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761578

RESUMO

Sense organs (eyes, ears, nose, tongue, and skin) provide senses of sight, hearing, smell, taste, and touch, respectively, to aid the survival, development, learning, and adaptation of humans and other animals (including fish). Amino acids (AAs) play an important role in the growth, development, and functions of the sense organs. Recent work has identified receptor-mediated mechanisms responsible for the chemosensory transduction of five basic taste qualities (sweet, sour, bitter, umami and salty tastes). Abnormal metabolism of AAs result in a structural deformity of tissues and their dysfunction. To date, there is a large database for AA metabolism in the eye and skin under normal (e.g., developmental changes and physiological responses) and pathological (e.g., nutritional and metabolic diseases, nutrient deficiency, infections, and cancer) conditions. Important metabolites of AAs include nitric oxide and polyamines (from arginine), melanin and dopamine (from phenylalanine and tyrosine), and serotonin and melatonin (from tryptophan) in both the eye and the skin; γ-aminobutyrate (from glutamate) in the retina; and urocanic acid and histamine (from histidine) in the skin. At present, relatively little is known about the synthesis or catabolism of AAs in the ears, nose, and tongue. Future research should be directed to: (1) address this issue with regard to healthy ageing, nasal and sinus cancer, the regulation of food intake, and oral cavity health; and (2) understand how prenatal and postnatal nutrition and environmental pollution affect the growth, development and health of the sense organs, as well as their expression of genes (including epigenetics) and proteins in humans and other animals.


Assuntos
Aminoácidos/metabolismo , Órgãos dos Sentidos/metabolismo , Órgãos dos Sentidos/fisiologia , Animais , Humanos
16.
Ecotoxicol Environ Saf ; 202: 111011, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800236

RESUMO

Boron (B) deficiency and surplus are the main factors that affect plant growth and yield. A better understanding of the response mechanisms of plant reproductive organs to stress induced by B deficiency and surplus could provide new insights to potential strategies for improving seed yield and quality. In this study, we aimed to elucidate the mechanisms of tolerance to B-induced stress in the reproductive organs of alfalfa (Medicago sativa L. cv. 'Aohan'). We initially used five B concentrations (0 mg B L-1, 400 mg B L-1, 800 mg B L-1, 1200 mg B L-1, and 1600 mg B L-1) to determine the B deficient, sufficient, and surplus levels in the field. Secondly, we examined changes in metabolite profiles of alfalfa 'Aohan' reproductive organs in response to B deficiency (0 mg B L-1), B sufficiency (800 mg B L-1), and B surplus (1600 mg B L-1) conditions using gas chromatography-mass spectrometry (GC-MS). Flowers and seeds from alfalfa 'Aohan' showed different metabolite profiles and resistance capacity under B deficiency and surplus conditions. B deficiency led to the excessive accumulation of sugars and phenolic compounds in alfalfa 'Aohan' and seeds, respectively, thus causing abscission or the abortion of reproductive organs. In contrast, B surplus severely reduced the levels of metabolites associated with amino acid and carbohydrate metabolism, resulting in the flowers falling and, therefore, low seed yield. Overall, B deficiency predominantly reduced seed yield and quality of alfalfa 'Aohan', while B surplus mainly affected seed yield of alfalfa 'Aohan'.


Assuntos
Boro/deficiência , Boro/toxicidade , Células Germinativas Vegetais/efeitos dos fármacos , Medicago sativa/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Poluentes do Solo/toxicidade , Aminoácidos/metabolismo , Metabolismo dos Carboidratos/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Células Germinativas Vegetais/metabolismo , Medicago sativa/metabolismo , Metabolômica , Sementes/metabolismo , Poluentes do Solo/metabolismo
17.
Int Heart J ; 61(4): 739-747, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32684600

RESUMO

The metabolism of branched-chain amino acids (BCAAs) is reported to change in heart failure (HF) and correlate with cardiac function. However, the effect of BCAAs on HF remains controversial. We investigate the prognostic value of the plasma BCAA level in nonischemic dilated cardiomyopathy (NIDCM).This study enrolled 39 NIDCM patients, who underwent plasma amino acid (AA) analysis. The ratio of BCAAs to total AAs was calculated. All patients were divided into two groups at the median of BCAA/total AA ratio; high BCAA/total AA group (≥ 0.15, n = 20) and low BCAA/total AA group (< 0.15, n = 19). A cardiac event was defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia.The mean age was 51.1 ± 12.3 years and left ventricular ejection fraction (LVEF) was 32.7 ± 10.1%. In the low BCAA/total AA group, the body mass index and the total cholesterol level were lower than in the high BCAA/total AA group. The BCAA/total AA ratio was positively correlated with LVEF (r = 0.35, P = 0.031) and negatively correlated with brain natriuretic peptide (r = -0.37, P = 0.020). The low BCAA/total AA group had a lower cardiac event-free rate (5-year: 100% versus 73%; P = 0.019). In univariate analysis, angiotensin converting enzyme inhibitor or angiotensin II receptor blocker (hazard ratio: 0.045, P = 0.0014), hemoglobin (hazard ratio: 0.49 per 1 g/dL, P = 0.0022), and BCAA/total AA ratio < 0.15 (hazard ratio: not available, P = 0.0066) were major predictors for cardiac events.The BCAA/total AA ratio might be a useful predictor for future cardiac events in patients with NIDCM.


Assuntos
Aminoácidos/sangue , Cardiomiopatia Dilatada/sangue , Adulto , Idoso , Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Nature ; 583(7815): 303-309, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32612236

RESUMO

Mammalian cells reorganize their proteomes in response to nutrient stress through translational suppression and degradative mechanisms using the proteasome and autophagy systems1,2. Ribosomes are central targets of this response, as they are responsible for translation and subject to lysosomal turnover during nutrient stress3-5. The abundance of ribosomal (r)-proteins (around 6% of the proteome; 107 copies per cell)6,7 and their high arginine and lysine content has led to the hypothesis that they are selectively used as a source of basic amino acids during nutrient stress through autophagy4,7. However, the relative contributions of translational and degradative mechanisms to the control of r-protein abundance during acute stress responses is poorly understood, as is the extent to which r-proteins are used to generate amino acids when specific building blocks are limited7. Here, we integrate quantitative global translatome and degradome proteomics8 with genetically encoded Ribo-Keima5 and Ribo-Halo reporters to interrogate r-protein homeostasis with and without active autophagy. In conditions of acute nutrient stress, cells strongly suppress the translation of r-proteins, but, notably, r-protein degradation occurs largely through non-autophagic pathways. Simultaneously, the decrease in r-protein abundance is compensated for by a reduced dilution of pre-existing ribosomes and a reduction in cell volume, thereby maintaining the density of ribosomes within single cells. Withdrawal of basic or hydrophobic amino acids induces translational repression without differential induction of ribophagy, indicating that ribophagy is not used to selectively produce basic amino acids during acute nutrient stress. We present a quantitative framework that describes the contributions of biosynthetic and degradative mechanisms to r-protein abundance and proteome remodelling in conditions of nutrient stress.


Assuntos
Nutrientes/metabolismo , Biossíntese de Proteínas , Ribossomos/metabolismo , Estresse Fisiológico , Aminoácidos/deficiência , Aminoácidos/metabolismo , Autofagia , Linhagem Celular , Homeostase , Humanos , Proteólise , Proteoma/biossíntese , Proteoma/metabolismo , Proteômica , Purinas/metabolismo , Análise de Célula Única , Estresse Fisiológico/genética
19.
Acta Crystallogr C Struct Chem ; 76(Pt 7): 663-672, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32624513

RESUMO

The reactivity of the cobalt(III) complexes dichlorido[tris(2-aminoethyl)amine]cobalt(III) chloride, [CoCl2(tren)]Cl, and dichlorido(triethylenetetramine)cobalt(III) chloride, [CoCl2(trien)]Cl, towards different amino acids (L-proline, L-asparagine, L-histidine and L-aspartic acid) was explored in detail. This study presents the crystal structures of three amino acidate cobalt(III) complexes, namely, (L-prolinato-κ2N,O)[tris(2-aminoethyl)amine-κ4N,N',N'',N''']cobalt(III) diiodide monohydrate, [Co(C5H8NO2)(C6H18N4)]I2·H2O, I, (L-asparaginato-κ2N,O)[tris(2-aminoethyl)amine-κ4N,N',N'',N''']cobalt(III) chloride perchlorate, [Co(C4H7N2O3)(C6H18N4)](Cl)(ClO4), II, and (L-prolinato-κ2N,O)(triethylenetetramine-κ4N,N',N'',N''')cobalt(III) chloride perchlorate, [Co(C4H7N2O3)(C6H18N4)](Cl)(ClO4), V. The syntheses of the complexes were followed by characterization using UV-Vis spectroscopy of the reaction mixtures and the initial rates of reaction were obtained by calculating the slopes of absorbance versus time plots. The initial rates suggest a stronger reactivity and hence greater affinity of the cobalt(III) complexes towards basic amino acids. The biocompatibility of the complexes was also assessed by evaluating the cytotoxicity of the complexes on cultured normal human fibroblast cells (WS1) in vitro. The compounds were found to be nontoxic after 24 h of incubation at concentrations up to 25 mM.


Assuntos
Cobalto/química , Complexos de Coordenação/química , Histidina/química , Aminoácidos/química , Cristalografia por Raios X , Ligantes , Percloratos/química
20.
PLoS One ; 15(7): e0232072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645038

RESUMO

The vasculature within a tumor is highly disordered both structurally and functionally. Endothelial cells that comprise the vasculature are poorly connected causing vessel leakage and exposing the endothelium to a hypoxic microenvironment. Therefore, most anti-angiogenic therapies are generally inefficient and result in acquired resistance to increased hypoxia due to elimination of the vasculature. Recent studies have explored the efficacy of targeting metabolic pathways in tumor cells in combination with anti-angiogenic therapy. However, the metabolic alterations of endothelial cells in response to hypoxia have been relatively unexplored. Here, we measured polar metabolite levels in microvascular endothelial cells exposed to short- and long-term hypoxia with the goal of identifying metabolic vulnerabilities that can be targeted to normalize tumor vasculature and improve drug delivery. We found that many amino acid-related metabolites were altered by hypoxia exposure, especially within alanine-aspartate-glutamate, serine-threonine, and cysteine-methionine metabolism. Additionally, there were significant changes in de novo pyrimidine synthesis as well as glutathione and taurine metabolism. These results provide key insights into the metabolic alterations that occur in endothelial cells in response to hypoxia, which serve as a foundation for future studies to develop therapies that lead to vessel normalization and more efficient drug delivery.


Assuntos
Hipóxia Celular , Células Endoteliais/metabolismo , Redes e Vias Metabólicas , Aminoácidos/metabolismo , Ácido Aspártico/metabolismo , Linhagem Celular , Cisteína/metabolismo , Células HEK293 , Humanos , Microvasos/metabolismo , Nucleotídeos/metabolismo
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