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Essential amino acids

Kshipra Singh, Nicole T Al-Greene, Thomas G Verriere, Lori A Coburn, Mohammad Asim, Daniel P Barry, Margaret M Allaman, Dana M Hardbower, Alberto G Delgado, M Blanca Piazuelo, Bruce A Vallance, Alain P Gobert, Keith T Wilson
Solute carrier family 7 member 2 (SLC7A2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in immune responses to pathogens. We assessed the role of SLC7A2 in murine infection with Citrobacter rodentium, an attaching and effacing enteric pathogen that causes colitis. Induction of SLC7A2 was upregulated in colitis tissues, and localized predominantly to colonic epithelial cells. Compared to wild-type mice, Slc7a2-/-mice infected with C. rodentium had improved survival and decreased weight loss, colon weight, and histologic injury; this was associated with decreased colonic macrophages, dendritic cells, granulocytes, and Th1 and Th17 cells...
October 2016: PLoS Pathogens
Jennifer Hochheim, Angela Kranz, Karin Krumbach, Sascha Sokolowsky, Lothar Eggeling, Stephan Noack, Marco Bocola, Michael Bott, Jan Marienhagen
OBJECTIVES: To explore systemic effects of mutations in the UDP-N-acetylmuramoylalanyl-D-glutamate 2,6-diaminopimelate ligase (MurE) of Corynebacterium glutamicum, that leads to extracellular L-lysine accumulation by this bacterium. RESULTS: The analysis of a mutant cohort of C. glutamicum strains carrying all possible 20 amino acids at position 81 of MurE revealed unexpected effects on cellular properties. With increasing L-lysine accumulation the growth rate of the producing strain is reduced...
October 25, 2016: Biotechnology Letters
Jordana K Thibado, Ashley N Martfeld, Denise V Greathouse, Roger E Koeppe
An essential component of mammalian cells, cholesterol exerts significant influence on the physical properties of the cell membrane and in turn its constituents, including membrane proteins. Although sparse, polar amino-acid residues are highly conserved in membrane proteins and play pivotal roles in determining specific structural and functional properties. To gain greater understanding of particular polar residues in the membrane environment, we have examined two specific "guest" Arg residues within a well-defined and deuterium-labeled "host" framework provided by the transmembrane helical peptide GWALP23 (acetyl-GGALWLALALALALALALWLAGA-amide)...
October 26, 2016: Biochemistry
Stephanie M Cossette, Vijesh J Bhute, Xiaoping Bao, Leanne M Harmann, Mark A Horswill, Indranil Sinha, Adam Gastonguay, Shabnam Pooya, Michelle Bordas, Suresh N Kumar, Shama P Mirza, Sean Palecek, Jennifer Strande, Ramani Ramchandran
BACKGROUND: -Cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. Our lab has previously shown that sucrose non-fermenting related kinase (SNRK) enzyme, which belongs to the AMP-activated kinase (AMPK) family, was essential for cardiac metabolism in mammals. Snrk global homozygous knockout (KO) mice die at postnatal day 0, and conditional deletion of Snrk in cardiomyocytes (Snrk cmcKO) leads to cardiac failure, and death by 8-10 months...
October 25, 2016: Circulation. Cardiovascular Genetics
Tathyana Mar Amorim Franco, Subray S Hegde, John S Blanchard
The biosynthetic pathway of the branched-chain amino acids is essential for M. tuberculosis growth and survival. We report here the kinetic and chemical mechanism of the pyridoxal 5'-phosphate (PLP)-dependent branched-chain aminotransferase, IlvE, from M. tuberculosis (MtIlvE). This enzyme is responsible for the final step of the synthesis of the branched-chain amino acids isoleucine, leucine and valine. As seen in other aminotransferases, MtIlvE displays a ping-pong kinetic mechanism. pK values were identified from the pH dependence on V as well as V/K, indicating that the phosphate ester of the PLP cofactor, as well as the α-amino group from L-glutamate and the active site Lys204, play roles in acid-base catalysis and binding, respectively...
October 25, 2016: Biochemistry
Bethany G Caulkins, Robert P Young, Ryan A Kudla, Chen Yang, Thomas J Bittbauer, Baback Bastin, Eduardo Hilario, Li Fan, Michael J Marsella, Michael F Dunn, Leonard J Mueller
Carbanionic intermediates play a central role in the catalytic transformations of amino acids performed by pyridoxal-5'-phosphate (PLP)-dependent enzymes. Here, we make use of NMR crystallography - the synergistic combination of solid-state nuclear magnetic resonance, X-ray crystallography, and computational chemistry - to interrogate a carbanionic/quinonoid intermediate analogue in the β-subunit active site of the PLP-requiring enzyme tryptophan synthase. The solid-state NMR chemical shifts of the PLP pyridine ring nitrogen and additional sites, coupled with first principles computational models, allow a detailed model of protonation states for ionizable groups on the cofactor, substrates, and nearby catalytic residues to be established...
October 25, 2016: Journal of the American Chemical Society
Zdenka Cicova, Mario Dejung, Tomas Skalicky, Nicole Eisenhuth, Steffen Hanselmann, Brooke Morriswood, Luisa M Figueiredo, Falk Butter, Christian J Janzen
Trypanosomes are masters of adaptation to different host environments during their complex life cycle. Large-scale proteomic approaches provide information on changes at the cellular level, and in a systematic way. However, detailed work on single components is necessary to understand the adaptation mechanisms on a molecular level. Here, we have performed a detailed characterization of a bloodstream form (BSF) stage-specific putative flagellar host adaptation factor Tb927.11.2400, identified previously in a SILAC-based comparative proteome study...
October 25, 2016: Scientific Reports
Hamidreza Kavianpour, Mahdi Vasighi
Nowadays, having knowledge about cellular attributes of proteins has an important role in pharmacy, medical science and molecular biology. These attributes are closely correlated with the function and three-dimensional structure of proteins. Knowledge of protein structural class is used by various methods for better understanding the protein functionality and folding patterns. Computational methods and intelligence systems can have an important role in performing structural classification of proteins. Most of protein sequences are saved in databanks as characters and strings and a numerical representation is essential for applying machine learning methods...
October 24, 2016: Amino Acids
Miaomiao Bai, Hongnan Liu, Kang Xu, Abimbola Oladele Oso, Xin Wu, Gang Liu, Myrlene Carine B Tossou, Naif Abdullah Al-Dhabi, Veeramuthu Duraipandiyan, Qianyun Xi, Yinlong Yin
Tryptophan, a nutritionally essential amino acid, is active in the regulation of immune responses in animals. The products of tryptophan metabolism, such as indoleamine 2,3-dioxygenase, kynurenine, quinolinic acid, and melatonin, may improve immunity in an organism and induce anti-inflammatory responses. The immune tolerance processes mediated by tryptophan metabolites are not well understood. Recent studies have reported that the enzymes that break down tryptophan through the kynurenine metabolic pathway are found in numerous cell types, including immunocytes...
October 24, 2016: Amino Acids
Katrien H P Van Petegem, David Renault, Robby Stoks, Dries Bonte
Despite an increasing number of studies documenting life-history evolution during range expansions or shifts, we lack a mechanistic understanding of the underlying physiological processes. In this explorative study, we used a metabolomics approach to study physiological changes associated with the recent range expansion of the two-spotted spider mite (Tetranychus urticae). Mite populations were sampled along a latitudinal gradient from range core to edge and reared under benign common garden conditions for two generations...
September 2016: Ecology and Evolution
Féfé Khuabi Matondo, Kikuni Takaisi, Adolphine Bedi Nkuadiolandu, Aimé Kazadi Lukusa, Michel Ntetani Aloni
Aim. Despite high levels of malnutrition, there is still very little information on the nutritional benefits of Spirulina, a natural alga that provides essential amino acids, rare essential lipids, and numerous minerals and vitamins, to undernourished children in the world. Methods. We carried out a prospective study of 50 children aged between six and 60 months. The intervention group consisted of 16 children who received 10 g of Spirulina daily, as well as the local diet administered by the nutritional centre, and the control group of 34 children who just received the local diet...
2016: International Journal of Pediatrics
Milo B Fasken, Jillian S Losh, Sara W Leung, Sergine Brutus, Brittany Avin, Jillian C Vaught, Jennifer Potter-Birriel, Taylor Craig, Graeme L Conn, Katherine Mills-Lujan, Anita H Corbett, Ambro van Hoof
Pontocerebellar Hypoplasia type 1b (PCH1b) is an autosomal recessive disorder that causes cerebellar hypoplasia and spinal motor neuron degeneration leading to mortality in early childhood. PCH1b is caused by mutations in the RNA exosome subunit gene, EXOSC3 The RNA exosome is an evolutionarily conserved complex, consisting of nine different core subunits and one or two 3'-5' exoribonuclease subunits, that mediates several RNA degradation and processing steps. The goal of this study is to assess the functional consequences of the amino acid substitutions that have been identified in EXOSC3 in PCH1b patients...
October 24, 2016: Genetics
Cuixia Gao, Bingxian Yang, Dandan Zhang, Meng Chen, Jingkui Tian
BACKGROUND: Indole alkaloids, which characteristically contain an indole nucleus, have pharmaceutical potential in a diverse range of applications. UV-B can elicit the accumulation of indole alkaloids. The indole alkaloid (6-hydroxyl-1H-indol-3-yl) carboxylic acid methyl ester with cytotoxic activity was found to accumulate in Clematis terniflora DC. leaves after exposure to high level of UV-B irradiation and the dark. However, a more in-depth analysis of the process behind this response has not yet been performed...
October 24, 2016: BMC Plant Biology
Anna Hojka-Osinska, Lucyna Budzko, Agnieszka Zmienko, Agnieszka Rybarczyk, Patrick Maillard, Agata Budkowska, Marek Figlerowicz, Paulina Jackowiak
Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to the immune and metabolic cellular responses to infection. Pathway enrichment analysis indicated that HCV induced an increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism...
October 25, 2016: Acta Biochimica Polonica
Hongtao Guo, Xuyan Niu, Yan Gu, Cheng Lu, Cheng Xiao, Kevin Yue, Ge Zhang, Xiaohua Pan, Miao Jiang, Yong Tan, Hongwei Kong, Zhenli Liu, Guowang Xu, Aiping Lu
Pattern classification is a key approach in Traditional Chinese Medicine (TCM), and it is used to classify the patients for intervention selection accordingly. TCM cold and heat patterns, two main patterns of rheumatoid arthritis (RA) had been explored with systems biology approaches. Different regulations of apoptosis were found to be involved in cold and heat classification in our previous works. For this study, the metabolic profiling of plasma was explored in RA patients with typical TCM cold or heat patterns by integrating liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) platforms in conjunction with the Ingenuity Pathway Analysis (IPA) software...
October 21, 2016: International Journal of Molecular Sciences
Jian Zhang, Haiting Chai, Bo Gao, Guifu Yang, Zhiqiang Ma
Heme is an essential biomolecule that widely exists in numerous extant organisms. Accurately identifying heme binding residues (HEMEs) is of great importance in disease progression and drug development. In this study, a novel predictor named HEMEsPred was proposed for predicting HEMEs. First, several sequence- and structure-based features, including amino acid composition, motifs, surface preferences and secondary structure, were collected to construct feature matrices. Second, a novel fast-adaptive ensemble learning scheme was designed to overcome the serious class-imbalance problem as well as to enhance the prediction performance...
October 4, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Alberto Vázquez-Salazar, George Tan, Amanda Stockton, Renato Fani, Arturo Becerra, Antonio Lazcano
The five-membered heterocyclic imidazole group, which is an essential component of purines, histidine and many cofactors, has been abiotically synthesized in different model experiments that attempt to simulate the prebiotic environment. The evolutionary significance of imidazoles is highlighted not only by its presence in nucleic acid components and in histidine, but also by experimental reports of its ability to restore the catalytic activity of ribozymes. However, as of today there are no reports of histidine in carbonaceous chondrites, and although the abiotic synthesis of His reported by Shen et al...
October 22, 2016: Origins of Life and Evolution of the Biosphere
Bo Lönnerdal, Peter Erdmann, Sagar K Thakkar, Julien Sauser, Frédéric Destaillats
The protein content of breast milk provides a foundation for estimating protein requirements of infants. Because it serves as a guideline for regulatory agencies issuing regulations for infant formula composition, it is critical that information on the protein content of breast milk is reliable. We have therefore carried out a meta-analysis of the protein and amino acid contents of breast milk and how they evolve during lactation. As several bioactive proteins are not completely digested in the infant and therefore represent "non-utilizable" protein, we evaluated the quantity, mechanism of action and digestive fate of several major breast milk proteins...
June 21, 2016: Journal of Nutritional Biochemistry
Vasanthanathan Poongavanam, Jacob Kongsted
The high rate of drug resistance as well as the complex biochemical process of the parasite reproduction cycle makes development of new drugs for malaria a very important but challenging task. Falcipain 2 (FL2) and Falcipain 3 (FL3) are the major cysteine protease enzymes that play a central role in providing essential amino acids for the parasite's protein biosynthesis through the hemoglobin hydrolysis process. Selective inhibition of these enzymes is considered as a promising chemotherapeutic target. In the present investigation, the highly efficient linear interaction energy (LIE) method has been parameterized for binding affinity predictions and assessed with a set of 244 compounds for FL2 and FL3 inhibition...
June 26, 2016: Journal of Molecular Graphics & Modelling
Ning Jia, Qinru Sun, Qian Su, Shaokang Dang, Guomin Chen
Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS). Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM) was employed for testing the cognitive function in the one-month-old rat offspring...
October 13, 2016: Redox Biology
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