Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34.197
Filtrar
1.
PLoS Comput Biol ; 16(9): e1008103, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32956350

RESUMO

Highly coordinated water molecules are frequently an integral part of protein-protein and protein-ligand interfaces. We introduce an updated energy model that efficiently captures the energetic effects of these ordered water molecules on the surfaces of proteins. A two-stage method is developed in which polar groups arranged in geometries suitable for water placement are first identified, then a modified Monte Carlo simulation allows highly coordinated waters to be placed on the surface of a protein while simultaneously sampling amino acid side chain orientations. This "semi-explicit" water model is implemented in Rosetta and is suitable for both structure prediction and protein design. We show that our new approach and energy model yield significant improvements in native structure recovery of protein-protein and protein-ligand docking discrimination tests.


Assuntos
Sítios de Ligação/fisiologia , Simulação de Acoplamento Molecular , Ligação Proteica/fisiologia , Proteínas , Água , Algoritmos , Aminoácidos/química , Aminoácidos/metabolismo , Ligação de Hidrogênio , Ligantes , Método de Monte Carlo , Proteínas/química , Proteínas/metabolismo , Água/química , Água/metabolismo
2.
PLoS Pathog ; 16(9): e1008328, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32936835

RESUMO

Candida albicans cells depend on the energy derived from amino acid catabolism to induce and sustain hyphal growth inside phagosomes of engulfing macrophages. The concomitant deamination of amino acids is thought to neutralize the acidic microenvironment of phagosomes, a presumed requisite for survival and initiation of hyphal growth. Here, in contrast to an existing model, we show that mitochondrial-localized NAD+-dependent glutamate dehydrogenase (GDH2) catalyzing the deamination of glutamate to α-ketoglutarate, and not the cytosolic urea amidolyase (DUR1,2), accounts for the observed alkalization of media when amino acids are the sole sources of carbon and nitrogen. C. albicans strains lacking GDH2 (gdh2-/-) are viable and do not extrude ammonia on amino acid-based media. Environmental alkalization does not occur under conditions of high glucose (2%), a finding attributable to glucose-repression of GDH2 expression and mitochondrial function. Consistently, inhibition of oxidative phosphorylation or mitochondrial translation by antimycin A or chloramphenicol, respectively, prevents alkalization. GDH2 expression and mitochondrial function are derepressed as glucose levels are lowered from 2% (~110 mM) to 0.2% (~11 mM), or when glycerol is used as primary carbon source. Using time-lapse microscopy, we document that gdh2-/- cells survive, filament and escape from primary murine macrophages at rates indistinguishable from wildtype. In intact hosts, such as in fly and murine models of systemic candidiasis, gdh2-/- mutants are as virulent as wildtype. Thus, although Gdh2 has a critical role in central nitrogen metabolism, Gdh2-catalyzed deamination of glutamate is surprisingly dispensable for escape from macrophages and virulence. Consistently, using the pH-sensitive dye (pHrodo), we observed no significant difference between wildtype and gdh2-/- mutants in phagosomal pH modulation. Following engulfment of fungal cells, the phagosomal compartment is rapidly acidified and hyphal growth initiates and sustained under consistently acidic conditions within phagosomes. Together, our results demonstrate that amino acid-dependent alkalization is not essential for hyphal growth, survival in macrophages and hosts. An accurate understanding of the microenvironment within macrophage phagosomes and the metabolic events underlying the survival of phagocytized C. albicans cells and their escape are critical to understanding the host-pathogen interactions that ultimately determine the pathogenic outcome.


Assuntos
Candida albicans/imunologia , Candidíase/imunologia , Drosophila melanogaster/imunologia , Glutamato Desidrogenase/metabolismo , Macrófagos/imunologia , Aminoácidos/genética , Aminoácidos/metabolismo , Animais , Candida albicans/patogenicidade , Candidíase/metabolismo , Candidíase/microbiologia , Drosophila melanogaster/metabolismo , Drosophila melanogaster/microbiologia , Feminino , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Glutamato Desidrogenase/genética , Interações Hospedeiro-Patógeno , Concentração de Íons de Hidrogênio , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Nitrogênio , Fagossomos/imunologia , Fagossomos/metabolismo , Fagossomos/microbiologia , Virulência
3.
Nat Commun ; 11(1): 4880, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978375

RESUMO

Through advanced mechanistic modeling and the generation of large high-quality datasets, machine learning is becoming an integral part of understanding and engineering living systems. Here we show that mechanistic and machine learning models can be combined to enable accurate genotype-to-phenotype predictions. We use a genome-scale model to pinpoint engineering targets, efficient library construction of metabolic pathway designs, and high-throughput biosensor-enabled screening for training diverse machine learning algorithms. From a single data-generation cycle, this enables successful forward engineering of complex aromatic amino acid metabolism in yeast, with the best machine learning-guided design recommendations improving tryptophan titer and productivity by up to 74 and 43%, respectively, compared to the best designs used for algorithm training. Thus, this study highlights the power of combining mechanistic and machine learning models to effectively direct metabolic engineering efforts.


Assuntos
Aprendizado de Máquina , Engenharia Metabólica/métodos , Saccharomyces cerevisiae/metabolismo , Triptofano/metabolismo , Algoritmos , Aminoácidos/metabolismo , Fenômenos Bioquímicos , Técnicas Biossensoriais , Genótipo , Redes e Vias Metabólicas , Modelos Biológicos , Fenótipo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento
4.
Nat Commun ; 11(1): 4236, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843654

RESUMO

The impact of commensal bacteria on the host arises from complex microbial-diet-host interactions. Mapping metabolic interactions in gut microbial communities is therefore key to understand how the microbiome influences the host. Here we use an interdisciplinary approach including isotope-resolved metabolomics to show that in Drosophila melanogaster, Acetobacter pomorum (Ap) and Lactobacillus plantarum (Lp) a syntrophic relationship is established to overcome detrimental host diets and identify Ap as the bacterium altering the host's feeding decisions. Specifically, we show that Ap uses the lactate produced by Lp to supply amino acids that are essential to Lp, allowing it to grow in imbalanced diets. Lactate is also necessary and sufficient for Ap to alter the fly's protein appetite. Our data show that gut bacterial communities use metabolic interactions to become resilient to detrimental host diets. These interactions also ensure the constant flow of metabolites used by the microbiome to alter reproduction and host behaviour.


Assuntos
Dieta , Drosophila melanogaster/microbiologia , Drosophila melanogaster/fisiologia , Microbioma Gastrointestinal/fisiologia , Acetobacter/crescimento & desenvolvimento , Acetobacter/metabolismo , Aminoácidos/deficiência , Aminoácidos/metabolismo , Animais , Apetite , Feminino , Preferências Alimentares , Interações entre Hospedeiro e Microrganismos , Ácido Láctico/metabolismo , Lactobacillus plantarum/crescimento & desenvolvimento , Lactobacillus plantarum/metabolismo , Redes e Vias Metabólicas , Metabolômica , Consórcios Microbianos , Reprodução
5.
PLoS One ; 15(8): e0237744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841246

RESUMO

Both the Mediterranean (MED) species of the Bemisia tabaci whitefly complex and the greenhouse whitefly (Trialeurodes vaporariorum, TV) are important agricultural pests. The two species of whiteflies differ in many aspects such as morphology, geographical distribution, host plant range, plant virus transmission, and resistance to insecticides. However, the molecular basis underlying their differences remains largely unknown. In this study, we analyzed the genetic divergences between the transcriptomes of MED and TV. In total, 2,944 pairs of orthologous genes were identified. The average identity of amino acid sequences between the two species is 93.6%. The average nonsynonymous (Ka) and synonymous (Ks) substitution rates and the ratio of Ka/Ks of the orthologous genes are 0.0389, 2.23 and 0.0204, respectively. The low average Ka/Ks ratio indicates that orthologous genes tend to be under strong purified selection. The most divergent gene classes are related to the metabolisms of xenobiotics, cofactors, vitamins and amino acids, and this divergence may underlie the different biological characteristics between the two species of whiteflies. Genes of differential expression between the two species are enriched in carbohydrate metabolism and regulation of autophagy. These findings provide molecular clues to uncover the biological and molecular differences between the two species of whiteflies.


Assuntos
Produção Agrícola , Genes de Insetos/genética , Especiação Genética , Hemípteros/genética , Proteínas de Insetos/genética , Sequência de Aminoácidos/genética , Substituição de Aminoácidos/genética , Aminoácidos/metabolismo , Animais , Hemípteros/metabolismo , Proteínas de Insetos/metabolismo , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Região do Mediterrâneo , Anotação de Sequência Molecular , RNA-Seq , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Vitaminas/metabolismo , Xenobióticos/metabolismo
6.
PLoS Genet ; 16(8): e1008893, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32841241

RESUMO

All tRNAs are extensively modified, and modification deficiency often results in growth defects in the budding yeast Saccharomyces cerevisiae and neurological or other disorders in humans. In S. cerevisiae, lack of any of several tRNA body modifications results in rapid tRNA decay (RTD) of certain mature tRNAs by the 5'-3' exonucleases Rat1 and Xrn1. As tRNA quality control decay mechanisms are not extensively studied in other eukaryotes, we studied trm8Δ mutants in the evolutionarily distant fission yeast Schizosaccharomyces pombe, which lack 7-methylguanosine at G46 (m7G46) of their tRNAs. We report here that S. pombe trm8Δ mutants are temperature sensitive primarily due to decay of tRNATyr(GUA) and that spontaneous mutations in the RAT1 ortholog dhp1+ restored temperature resistance and prevented tRNA decay, demonstrating conservation of the RTD pathway. We also report for the first time evidence linking the RTD and the general amino acid control (GAAC) pathways, which we show in both S. pombe and S. cerevisiae. In S. pombe trm8Δ mutants, spontaneous GAAC mutations restored temperature resistance and tRNA levels, and the trm8Δ temperature sensitivity was precisely linked to GAAC activation due to tRNATyr(GUA) decay. Similarly, in the well-studied S. cerevisiae trm8Δ trm4Δ RTD mutant, temperature sensitivity was closely linked to GAAC activation due to tRNAVal(AAC) decay; however, in S. cerevisiae, GAAC mutations increased tRNA loss and exacerbated temperature sensitivity. A similar exacerbated growth defect occurred upon GAAC mutation in S. cerevisiae trm8Δ and other single modification mutants that triggered RTD. Thus, these results demonstrate a conserved GAAC activation coincident with RTD in S. pombe and S. cerevisiae, but an opposite impact of the GAAC response in the two organisms. We speculate that the RTD pathway and its regulation of the GAAC pathway is widely conserved in eukaryotes, extending to other mutants affecting tRNA body modifications.


Assuntos
Exorribonucleases/metabolismo , Processamento Pós-Transcricional do RNA , Estabilidade de RNA , RNA de Transferência/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , tRNA Metiltransferases/metabolismo , Aminoácidos/metabolismo , Evolução Molecular , Exorribonucleases/genética , RNA de Transferência/metabolismo , Schizosaccharomyces , Proteínas de Schizosaccharomyces pombe/genética , tRNA Metiltransferases/genética
7.
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
8.
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
9.
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
10.
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
11.
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
12.
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
13.
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
14.
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
15.
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
16.
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
17.
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
18.
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
19.
PLoS One ; 15(8): e0236249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804964

RESUMO

BACKGROUND: The insect predator Coccinella septempunctata can effectively control many types of pests, such as aphids, whiteflies, and small lepidopteran larvae. We previously found that C. septempunctata fed an artificial diet showed diminished biological properties(e.g. fecundity, egg hatching rate, survival rate, etc.) compared with those fed natural prey (Aphis craccivora), likely due to different nutritional characteristics of the diet. In this study, we used transcriptome sequencing analysis to identify nutrition- and metabolism-related genes of C. septempunctata that were differentially expressed depending on diet. METHODOLOGY/PRINCIPAL FINDINGS: The Illumina HiSeq2000 was used to sequence 691,942,058 total clean reads from artificial diet-fed and A. craccivora-fed C. septempunctata libraries, and the clean reads were assembled using Trinity de novo software (Tabel 2). Comparison of transcriptome sequences revealed that expression of 38,315 genes was affected by the artificial diet, and 1,182 of these genes showed a significant change in expression levels (FDR ≤ 0.05,|log2FC|≥1, "FC" stands for "fold change"). These differentially expressed genes (DEGs) were likely associated with the decreased egg laying capacity, hatching rate, longevity, and increased sex ratio (♀:♂) of adult C. septempunctata observed in the group fed the artificial diet. Furthermore, in the most DEGs metabolic pathways for C. septempunctata feeding on the artificial diet accumulated amino acid metabolic pathways, lipid metabolic pathways, and starch and glucose metabolism were down-regulated. CONCLUSIONS/SIGNIFICANCE: We found some differentially expressed genes and metabolic pathways are related to nutrition, from which a more informative feedback for diet formulation was obtained and the artificial diet could be more efficiently optimized.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal/genética , Afídeos , Besouros/fisiologia , Genes de Insetos , Comportamento Predatório/fisiologia , Aminoácidos/metabolismo , Animais , Regulação para Baixo , Fertilidade/fisiologia , Perfilação da Expressão Gênica , Glucose/metabolismo , Metabolismo dos Lipídeos/genética , Longevidade/fisiologia , Redes e Vias Metabólicas/genética , Controle Biológico de Vetores/métodos , Razão de Masculinidade , Amido/metabolismo , Sequenciamento Completo do Exoma
20.
PLoS One ; 15(7): e0236588, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706804

RESUMO

Xanthoceras sorbifolia, a medicinal and oil-rich woody plant, has great potential for biodiesel production. However, little study explores the link between gene expression level and metabolite accumulation of X. sorbifolia in response to cold stress. Herein, we performed both transcriptomic and metabolomic analyses of X. sorbifolia seedlings to investigate the regulatory mechanism of resistance to low temperature (4 °C) based on physiological profile analyses. Cold stress resulted in a significant increase in the malondialdehyde content, electrolyte leakage and activity of antioxidant enzymes. A total of 1,527 common differentially expressed genes (DEGs) were identified, of which 895 were upregulated and 632 were downregulated. Annotation of DEGs revealed that amino acid metabolism, glycolysis/gluconeogenesis, starch and sucrose metabolism, galactose metabolism, fructose and mannose metabolism, and the citrate cycle (TCA) were strongly affected by cold stress. In addition, DEGs within the plant mitogen-activated protein kinase (MAPK) signaling pathway and TF families of ERF, WRKY, NAC, MYB, and bHLH were transcriptionally activated. Through metabolomic analysis, we found 51 significantly changed metabolites, particularly with the analysis of primary metabolites, such as sugars, amino acids, and organic acids. Moreover, there is an overlap between transcript and metabolite profiles. Association analysis between key genes and altered metabolites indicated that amino acid metabolism and sugar metabolism were enhanced. A large number of specific cold-responsive genes and metabolites highlight a comprehensive regulatory mechanism, which will contribute to a deeper understanding of the highly complex regulatory program under cold stress in X. sorbifolia.


Assuntos
Resposta ao Choque Frio/genética , Metaboloma , Metabolômica/métodos , Sapindaceae/metabolismo , Transcriptoma , Aminoácidos/metabolismo , Catalase/metabolismo , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Malondialdeído/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Análise de Componente Principal , RNA de Plantas/genética , RNA de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sapindaceae/genética , Transdução de Sinais/genética , Superóxido Dismutase/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA