Amino Acids Regulate mTORC1 by an Obligate Two-step Mechanism*

PubMed Central

Dyachok, Julia; Earnest, Svetlana; Iturraran, Erica N.; Cobb, Melanie H.

2016-01-01

The mechanistic target of rapamycin complex 1 (mTORC1) coordinates cell growth with its nutritional, hormonal, energy, and stress status. Amino acids are critical regulators of mTORC1 that permit other inputs to mTORC1 activity. However, the roles of individual amino acids and their interactions in mTORC1 activation are not well understood. Here we demonstrate that activation of mTORC1 by amino acids includes two discrete and separable steps: priming and activation. Sensitizing mTORC1 activation by priming amino acids is a prerequisite for subsequent stimulation of mTORC1 by activating amino acids. Priming is achieved by a group of amino acids that includes l-asparagine, l-glutamine, l-threonine, l-arginine, l-glycine, l-proline, l-serine, l-alanine, and l-glutamic acid. The group of activating amino acids is dominated by l-leucine but also includes l-methionine, l-isoleucine, and l-valine. l-Cysteine predominantly inhibits priming but not the activating step. Priming and activating steps differ in their requirements for amino acid concentration and duration of treatment. Priming and activating amino acids use mechanisms that are distinct both from each other and from growth factor signaling. Neither step requires intact tuberous sclerosis complex of proteins to activate mTORC1. Concerted action of priming and activating amino acids is required to localize mTORC1 to lysosomes and achieve its activation. PMID:27587390

Molecular dynamics simulation studies of the interactions between ionic liquids and amino acids in aqueous solution.

PubMed

Tomé, Luciana I N; Jorge, Miguel; Gomes, José R B; Coutinho, João A P

2012-02-16

Although the understanding of the influence of ionic liquids (ILs) on the solubility behavior of biomolecules in aqueous solutions is relevant for the design and optimization of novel biotechnological processes, the underlying molecular-level mechanisms are not yet consensual or clearly elucidated. In order to contribute to the understanding of the molecular interactions established between amino acids and ILs in aqueous media, classical molecular dynamics (MD) simulations were performed for aqueous solutions of five amino acids with different structural characteristics (glycine, alanine, valine, isoleucine, and glutamic acid) in the presence of 1-butyl-3-methylimidazolium bis(trifluoromethyl)sulfonyl imide. The results from MD simulations enable to relate the properties of the amino acids, namely their hydrophobicity, to the type and strength of their interactions with ILs in aqueous solutions and provide an explanation for the direction and magnitude of the solubility phenomena observed in [IL + amino acid + water] systems by a mechanism governed by a balance between competitive interactions of the IL cation, IL anion, and water with the amino acids.

Interaction of Atmospheric-Pressure Air Microplasmas with Amino Acids as Fundamental Processes in Aqueous Solution

PubMed Central

Zhou, Renwu; Zhou, Rusen; Zhuang, Jinxing; Zong, Zichao; Zhang, Xianhui; Liu, Dongping; Bazaka, Kateryna; Ostrikov, Kostya

2016-01-01

Plasma medicine is a relatively new field that investigates potential applications of cold atmospheric-pressure plasmas in bioengineering, such as for bacterial inactivation and degradation of organic molecules in water. In order to enunciate mechanisms of bacterial inactivation at molecular or atomic levels, we investigated the interaction of atmospheric-pressure air microplasmas with amino acids in aqueous solution by using high-resolution mass spectrometry (HRMS). Results show that the oxidation effect of plasma-induced species on the side chains of the amino acids can be categorized into four types, namely hydroxylation, nitration, dehydrogenation and dimerization. In addition, relative activities of amino acids resulting from plasma treatment come in descending order as follows: sulfur-containing carbon-chain amino acids > aromatic amino acids > five-membered ring amino acids > basic carbon-chain amino acids. Since amino acids are building blocks of proteins vital to the growth and reproduction of bacteria, these results provide an insight into the mechanism of bacterial inactivation by plasma. PMID:27183129

Interaction of amino acids with the Au(111) surface: adsorption free energies from molecular dynamics simulations.

PubMed

Hoefling, Martin; Iori, Francesco; Corni, Stefano; Gottschalk, Kay-Eberhard

2010-06-01

Interactions of proteins with inorganic surfaces are of high importance in biological events and in modern biotechnological applications. Therefore, peptides have been engineered to recognize inorganic surfaces with high specificity. However, the underlying interactions are still not well understood. Here, we investigated the adsorption of amino acids as protein building blocks onto a Au(111) surface. In particular, using molecular dynamics simulations, we calculated the potential of mean force between all the 20 amino acids and the gold surface. We found a strong dependence of the binding affinities on the chemical character of the amino acids. Additionally, the interaction free energy is correlated with the propensity of amino acids to form beta-sheets, hinting at design principles for gold binding peptides and induction of beta-sheet formation near surfaces.

Enhanced detection of amino acids in hydrophilic interaction chromatography electrospray tandem mass spectrometry with carboxylic acids as mobile phase additives.

PubMed

Yin, Dengyang; Hu, Xunxiu; Liu, Dantong; Du, Wencheng; Wang, Haibo; Guo, Mengzhe; Tang, Daoquan

2017-06-01

Liquid chromatography coupled with mass spectrometry technique has been widely used in the analysis of biological targets such as amino acids, peptides, and proteins. In this work, eight common single carboxylic acids or diacids, which contain different pKa have been investigated as the additives to the analysis of amino acids. As the results, carboxylic acid additive can improve the signal intensity of acidity amino acids such as Asp and Glu and the chromatographic separation of basic amino acids such as Arg, His, and Lys. In particular, the diacids have better performance than single acids. The proposed mechanism is that the diacid has hydrogen bond interaction with amino acids to reduce their polarity/amphiprotic characteristics. Besides, oxalic acid has been found having better enhancement than phthalic acid by overall consideration. Therefore, we successfully quantified the 15 amino acids in Sepia bulk pharmaceutical chemical by using oxalic acid as the additive.

Exploiting Amino Acid Composition for Predicting Protein-Protein Interactions

PubMed Central

Roy, Sushmita; Martinez, Diego; Platero, Harriett; Lane, Terran; Werner-Washburne, Margaret

2009-01-01

Background Computational prediction of protein interactions typically use protein domains as classifier features because they capture conserved information of interaction surfaces. However, approaches relying on domains as features cannot be applied to proteins without any domain information. In this paper, we explore the contribution of pure amino acid composition (AAC) for protein interaction prediction. This simple feature, which is based on normalized counts of single or pairs of amino acids, is applicable to proteins from any sequenced organism and can be used to compensate for the lack of domain information. Results AAC performed at par with protein interaction prediction based on domains on three yeast protein interaction datasets. Similar behavior was obtained using different classifiers, indicating that our results are a function of features and not of classifiers. In addition to yeast datasets, AAC performed comparably on worm and fly datasets. Prediction of interactions for the entire yeast proteome identified a large number of novel interactions, the majority of which co-localized or participated in the same processes. Our high confidence interaction network included both well-studied and uncharacterized proteins. Proteins with known function were involved in actin assembly and cell budding. Uncharacterized proteins interacted with proteins involved in reproduction and cell budding, thus providing putative biological roles for the uncharacterized proteins. Conclusion AAC is a simple, yet powerful feature for predicting protein interactions, and can be used alone or in conjunction with protein domains to predict new and validate existing interactions. More importantly, AAC alone performs at par with existing, but more complex, features indicating the presence of sequence-level information that is predictive of interaction, but which is not necessarily restricted to domains. PMID:19936254

Interaction of metal ions and amino acids - Possible mechanisms for the adsorption of amino acids on homoionic smectite clays

NASA Technical Reports Server (NTRS)

Gupta, A.; Loew, G. H.; Lawless, J.

1983-01-01

A semiempirical molecular orbital method is used to characterize the binding of amino acids to hexahydrated Cu(2+) and Ni(2+), a process presumed to occur when they are adsorbed in the interlamellar space of homoionic smectite clays. Five alpha-amino acids, beta-alanine, and gamma-aminobutyric acid were used to investigate the metal ion and amino acid specificity in binding. It was assumed that the alpha, beta, and gamma-amino acids would bind as bidentate anionic ligands, forming either 1:1 or 1:2 six-coordinated five, six, and seven-membered-ring chelate complexes, respectively. Energies of complex formation, optimized geometries, and electron and spin distribution were determined; and steric constraints of binding of the amino acids to the ion-exchanged cations in the interlamellar spacing of a clay were examined. Results indicate that hexahydrated Cu(2+) forms more stable complexes than hexahydrated Ni(2+) with all the amino acids studied. However, among these amino acids, complex formation does not favor the adsorption of the biological subset. Calculated energetics of complex formation and steric constraints are shown to predict that 1:1 rather than 1:2 metal-amino acid complexes are generally favored in the clay.

Influence of the Amino Acid Sequence on Protein-Mineral Interactions in Soil

NASA Astrophysics Data System (ADS)

Chacon, S. S.; Reardon, P. N.; Purvine, S.; Lipton, M. S.; Washton, N.; Kleber, M.

2017-12-01

The intimate associations between protein and mineral surfaces have profound impacts on nutrient cycling in soil. Proteins are an important source of organic C and N, and a subset of proteins, extracellular enzymes (EE), can catalyze the depolymerization of soil organic matter (SOM). Our goal was to determine how variation in the amino acid sequence could influence a protein's susceptibility to become chemically altered by mineral surfaces to infer the fate of adsorbed EE function in soil. We hypothesized that (1) addition of charged amino acids would enhance the adsorption onto oppositely charged mineral surfaces (2) addition of aromatic amino acids would increase adsorption onto zero charged surfaces (3) Increase adsorption of modified proteins would enhance their susceptibility to alterations by redox active minerals. To test these hypotheses, we generated three engineered proxies of a model protein Gb1 (IEP 4.0, 6.2 kDA) by inserting either negatively charged, positively charged or aromatic amino acids in the second loop. These modified proteins were allowed to interact with functionally different mineral surfaces (goethite, montmorillonite, kaolinite and birnessite) at pH 5 and 7. We used LC-MS/MS and solution-state Heteronuclear Single Quantum Coherence Spectroscopy NMR to observe modifications on engineered proteins as a consequence to mineral interactions. Preliminary results indicate that addition of any amino acids to a protein increase its susceptibility to fragmentation and oxidation by redox active mineral surfaces, and alter adsorption to the other mineral surfaces. This suggest that not all mineral surfaces in soil may act as sorbents for EEs and chemical modification of their structure should also be considered as an explanation for decrease in EE activity. Fragmentation of proteins by minerals can bypass the need to produce proteases, but microbial acquisition of other nutrients that require enzymes such as cellulases, ligninases or phosphatases

PHYSIOLOGY OF THE AMINO ACIDS.

PubMed

VAN Slyke, D D

1942-03-13

We have followed the amino acids from their entrance into the alimentary tract in the form of food proteins through the successive steps of digestion, absorption into the blood stream and passage from the blood stream into the tissues, where they are concentrated by some unknown mechanism to many times their concentration in the blood plasma. We have seen something of the way in which certain of the amino acids can be transformed into one another in the body or synthesized from ammonia and keto acids. However, we have had to admit that our bodies can form in such ways only about half of the different amino acids that are required, and that the other half must be made for us by plants, bacteria or other organisms which have greater synthetic powers than we. And finally we have seen something of the manifold fates of the amino acids after they have entered our tissues; how they may be destroyed and their nitrogenous parts turned into urea in the liver before it is possible to put them to their more specialized uses, how their carbon fractions can be used to form glucose, how they may sacrifice themselves to protect us from toxic products, how they can serve as source material for certain vitamins, hormones and other compounds with physiological functions still to be identified, and how finally those amino acids which are not deflected to these various fates may enter into the proteins of the tissues and become for a time parts of our living structures.

Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors.

PubMed

Xu, Fengqi; Tanaka, Shigenori; Watanabe, Hirofumi; Shimane, Yasuhiro; Iwasawa, Misako; Ohishi, Kazue; Maruyama, Tadashi

2018-05-03

Measles virus (MV) causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM), CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH), we elucidated computationally the details of binding energies between the amino acid residues of MVH and those of the receptors with an ab initio fragment molecular orbital (FMO) method. The calculated inter-fragment interaction energies (IFIEs) revealed a number of significantly interacting amino acid residues of MVH that played essential roles in binding to the receptors. As predicted from previously reported experiments, some important amino-acid residues of MVH were shown to be common but others were specific to interactions with the three receptors. Particularly, some of the (non-polar) hydrophobic residues of MVH were found to be attractively interacting with multiple receptors, thus indicating the importance of the hydrophobic pocket for intermolecular interactions (especially in the case of Nectin-4). In contrast, the electrostatic interactions tended to be used for specific molecular recognition. Furthermore, we carried out FMO calculations for in silico experiments of amino acid mutations, finding reasonable agreements with virological experiments concerning the substitution effect of residues. Thus, the present study demonstrates that the electron-correlated FMO method is a powerful tool to search exhaustively for amino acid residues that contribute to interactions with receptor molecules. It is also applicable for designing inhibitors of MVH and engineered MVs for cancer therapy.

Interactions of aromatic amino acids with heterocyclic ligand: An IR spectroscopic study

NASA Astrophysics Data System (ADS)

Tyunina, E. Yu.; Badelin, V. G.; Tarasova, G. N.

2015-09-01

The interactions of L-phenylalanine and L-tryptophan with nicotinic acid and uracyl in an aqueous buffer solution at pH 7.35 were studied by IR spectroscopy. The contributions of various functional groups to the complexation of aromatic amino acids with heterocyclic ligands were determined from the IR spectra of the starting substances and their mixtures.

Developing a model of plant hormone interactions

PubMed Central

Wang, Yu Hua

2011-01-01

Plant growth and development is influenced by mutual interactions among plant hormones. The five classical plant hormones are auxins, cytokinins, gibberellins, abscisic acid and ethylene. They are small diffusible molecules that easily penetrate between cells. In addition, newer classes of plant hormones have been identified such as brassinosteroids, jasmonic acid, salicylic acid and various small proteins or peptides. These hormones also play important roles in the regulation of plant growth and development. This review begins with a brief summary of the current findings on plant hormones. Based on this knowledge, a conceptual model about interactions among plant hormones is built so as to link and develop an understanding of the diverse functions of different plant hormones as a whole in plants. PMID:21406974

Amino acid ionic liquids.

PubMed

Ohno, Hiroyuki; Fukumoto, Kenta

2007-11-01

The preparation of ionic liquids derived from amino acids, and their properties, are outlined. Since amino acids have both a carboxylic acid residue and an amino group in a single molecule, they can be used as either anions or cations. These groups are also useful in their ability to introduce functional group(s). Twenty different natural amino acids were used as anions, to couple with the 1-ethyl-3-methylimidazolium cation. The salts obtained were all liquid at room temperature. The properties of the resulting ionic liquids (AAILs) depend on the side groups of the amino acids involved. These AAILs, composed of an amino acid with some functional groups such as a hydrogen bonding group, a charged group, or an aromatic ring, had an increased glass transition (or melting) temperature and/or higher viscosity as a result of additional interactions among the ions. Viscosity is reduced and the decomposition temperature of imidazolium-type salts is improved by using the tetrabutylphosphonium cation. The chirality of AAILs was maintained even upon heating to 150 degrees C after acetylation of the free amino group. The amino group was also modified to introduce a strong acid group so as to form hydrophobic and chiral ionic liquids. Unique phase behavior of the resulting hydrophobic ionic liquids and water mixture is found; the mixture is clearly phase separated at room temperature, but the solubility of water in this IL increases upon cooling, to give a homogeneous solution. This phase change is reversible, and separation occurs again by raising the temperature a few degrees. It is extraordinary for an IL/water mixture to display such behavior with a lower critical solution temperature. Some likely applications are proposed for these amino acid derived ionic liquids.

Characterization of interaction between amino acids and fulvic-like organic matter by fluorescence spectroscopy combining thermodynamic calculation.

PubMed

Lin, Tao; Hou, Bingwei; Wang, Jian; Xu, Yaqun; Chen, Wei

2017-03-01

Dissolved organic matter (DOM), as a very fine colloidal suspension, could inevitably affect the transformation process of dissolved organic nitrogen (DON) in drinking water treatment. Tryptophan and tyrosine were used as representatives of DON to investigate the interactions between amino acids and fulvic-like components of fluorescent DOM using titration experiments. The fluorescence intensity decreased significantly with the increasing fulvic acid (FA) concentration, suggesting that FA could greatly quench the intrinsic fluorescence of amino acids such as tryptophan and tyrosine. The absolute spectrum peaks of amino acids (AA) were changed in the presence of FA, possibly being resulted from non-covalent interactions between amino acids and FA. The specific hydrogen bonding and van der Waals forces played dominant roles in the interactions according to the results of theoretical analysis and thermodynamic calculation. The distance between donor and acceptor was 1.25 and 1.14 nm for the FA-tyrosine and FA-tryptophan system, indicating the energy transfer from tyrosine or tryptophan to FA. The association constant (K) decreased with the increase of temperature and pH value, while the change of ionic strength had no obvious influence on K value.

Supernovae, neutrinos and the chirality of amino acids.

PubMed

Boyd, Richard N; Kajino, Toshitaka; Onaka, Takashi

2011-01-01

A mechanism for creating an enantioenrichment in the amino acids, the building blocks of the proteins, that involves global selection of one handedness by interactions between the amino acids and neutrinos from core-collapse supernovae is defined. The chiral selection involves the dependence of the interaction cross sections on the orientations of the spins of the neutrinos and the (14)N nuclei in the amino acids, or in precursor molecules, which in turn couple to the molecular chirality. It also requires an asymmetric distribution of neutrinos emitted from the supernova. The subsequent chemical evolution and galactic mixing would ultimately populate the Galaxy with the selected species. The resulting amino acids could either be the source thereof on Earth, or could have triggered the chirality that was ultimately achieved for Earth's proteinaceous amino acids.

Utilizing knowledge base of amino acids structural neighborhoods to predict protein-protein interaction sites.

PubMed

Jelínek, Jan; Škoda, Petr; Hoksza, David

2017-12-06

Protein-protein interactions (PPI) play a key role in an investigation of various biochemical processes, and their identification is thus of great importance. Although computational prediction of which amino acids take part in a PPI has been an active field of research for some time, the quality of in-silico methods is still far from perfect. We have developed a novel prediction method called INSPiRE which benefits from a knowledge base built from data available in Protein Data Bank. All proteins involved in PPIs were converted into labeled graphs with nodes corresponding to amino acids and edges to pairs of neighboring amino acids. A structural neighborhood of each node was then encoded into a bit string and stored in the knowledge base. When predicting PPIs, INSPiRE labels amino acids of unknown proteins as interface or non-interface based on how often their structural neighborhood appears as interface or non-interface in the knowledge base. We evaluated INSPiRE's behavior with respect to different types and sizes of the structural neighborhood. Furthermore, we examined the suitability of several different features for labeling the nodes. Our evaluations showed that INSPiRE clearly outperforms existing methods with respect to Matthews correlation coefficient. In this paper we introduce a new knowledge-based method for identification of protein-protein interaction sites called INSPiRE. Its knowledge base utilizes structural patterns of known interaction sites in the Protein Data Bank which are then used for PPI prediction. Extensive experiments on several well-established datasets show that INSPiRE significantly surpasses existing PPI approaches.

Codes in the codons: construction of a codon/amino acid periodic table and a study of the nature of specific nucleic acid-protein interactions.

PubMed

Benyo, B; Biro, J C; Benyo, Z

2004-01-01

The theory of "codon-amino acid coevolution" was first proposed by Woese in 1967. It suggests that there is a stereochemical matching - that is, affinity - between amino acids and certain of the base triplet sequences that code for those amino acids. We have constructed a common periodic table of codons and amino acids, where the nucleic acid table showed perfect axial symmetry for codons and the corresponding amino acid table also displayed periodicity regarding the biochemical properties (charge and hydrophobicity) of the 20 amino acids and the position of the stop signals. The table indicates that the middle (2/sup nd/) amino acid in the codon has a prominent role in determining some of the structural features of the amino acids. The possibility that physical contact between codons and amino acids might exist was tested on restriction enzymes. Many recognition site-like sequences were found in the coding sequences of these enzymes and as many as 73 examples of codon-amino acid co-location were observed in the 7 known 3D structures (December 2003) of endonuclease-nucleic acid complexes. These results indicate that the smallest possible units of specific nucleic acid-protein interaction are indeed the stereochemically compatible codons and amino acids.

Interactions of low molecular weight aromatic acids and amino acids with goethite, kaolinite and bentonite with or without organic matter coating

NASA Astrophysics Data System (ADS)

Gao, Jiajia; Jansen, Boris; Cerli, Chiara; Kalbitz, Karsten

2015-04-01

Interaction of organic matter molecules with the soil's solid phase is a key factor influencing the stabilization of carbon in soils and thus forms a crucial aspect of the global carbon cycle. While subject of much research attention so far, we still have much to learn about such interactions at the molecular level; in particular in the light of competition between different classes of organic molecules and in the presence of previously adsorbed soil organic matter. We studied the interaction of a group of low molecular weight (LMW) aromatic acids (salicylic, syringic, vanillic and ferulic acid) and amino acids (lysine, glutamic, leucine and phenylalanine) on goethite, kaolinite and bentonite with and without previously adsorbed dissolved organic matter (DOM). For this we used batch experiments at pH = 6.0 where some of the organic compounds were positively charged (i.e. lysine) or negatively charged (i.e. glutamic and salicylic acid) while the minerals also displayed positively (i.e. goethite) or negatively charged surfaces (i.e. bentonite). We found much higher sorption of salicylic acid and lysine than other compounds. On the bare minerals we found a great variety of sorption strength, with salicylic acid strongly adsorbed, while syringic, vanillic and ferulic acid showed little or no adsorption. For the amino acids, protonated lysine showed a stronger affinity to negatively charged kaolinite and bentonite than other amino acids. While deprotonated glutamic acid showed the strongest adsorption on goethite. Leucine and phenylalanine showed hardly any adsorption on any of the minerals. When present concurrently, amino acids decreased the sorption of salicylic acid on the three types of mineral, while the presence of LMW aromatic acids increased the sorption of lysine on kaolinite and bentonite and the sorption of glutamic acid on goethite. The presence of previously adsorbed DOM reduced the sorption of salicylic acid and lysine. The results confirm that

Supernovae, Neutrinos and the Chirality of Amino Acids

PubMed Central

Boyd, Richard N.; Kajino, Toshitaka; Onaka, Takashi

2011-01-01

A mechanism for creating an enantioenrichment in the amino acids, the building blocks of the proteins, that involves global selection of one handedness by interactions between the amino acids and neutrinos from core-collapse supernovae is defined. The chiral selection involves the dependence of the interaction cross sections on the orientations of the spins of the neutrinos and the 14N nuclei in the amino acids, or in precursor molecules, which in turn couple to the molecular chirality. It also requires an asymmetric distribution of neutrinos emitted from the supernova. The subsequent chemical evolution and galactic mixing would ultimately populate the Galaxy with the selected species. The resulting amino acids could either be the source thereof on Earth, or could have triggered the chirality that was ultimately achieved for Earth’s proteinaceous amino acids. PMID:21747686

CSF/plasma ratios of amino acids: reference data and transports in children.

PubMed

Akiyama, Tomoyuki; Kobayashi, Katsuhiro; Higashikage, Akihito; Sato, Junko; Yoshinaga, Harumi

2014-01-01

We intended to investigate the effects of age, gender, and medications on amino acid cerebrospinal fluid (CSF)/plasma ratios in children, and to determine whether amino acid transports across the blood-CSF barrier in children differ from those in adults. Amino acid concentrations measured by ion-exchange high-performance liquid chromatography were used (CSF from 99 children, simultaneously collected plasma from 76 children). Influence of age, gender, and medications on the amino acid CSF concentrations and CSF/plasma ratios were analyzed by linear multiple regression. Interactions of amino acid transports were analyzed by correlation analysis of CSF/plasma ratios. CSF/plasma ratios of serine, valine, histidine, and arginine were higher in younger children. The glutamate CSF/plasma ratio was higher in older children. Serine, alanine, threonine, valine, and histidine CSF/plasma ratios were lower in females. Glutamine, methionine, tyrosine, and phenylalanine CSF/plasma ratios were elevated with valproate therapy. Serine, threonine, valine, leucine, and tyrosine CSF/plasma ratios were lower with clobazam therapy. The asparagine CSF/plasma ratio was elevated with pyridoxal phosphate therapy. Transports of most essential neutral amino acids interacted with each other, as did neutral amino acids with low molecular weights. Cationic amino acids interacted with each other and some essential neutral amino acids. Acidic amino acids had no interactions with other amino acids. Age, gender, and anti-epileptic drugs affect amino acid CSF/plasma ratios in children. Transport interactions between amino acids in children showed no remarkable difference from those of adults and generally followed the substrate specificities of multiple amino acid transport systems. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Stardust, Supernovae and the Chirality of the Amino Acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyd, R N; Kajino, T; Onaka, T

A mechanism for creating enantiomerism in the amino acids, the building blocks of the proteins, that involves global selection of one chirality by interactions between the amino acids and neutrinos from core-collapse supernovae is described. The selection involves the dependence of the interaction cross sections on the orientations of the spins of the neutrinos and the 14N nuclei in the amino acids, or in precursor molecules, which in turn couple to the molecular chirality. The subsequent chemical evolution and galactic mixing would ultimately populate the Galaxy with the selected species. The resulting amino acids could either be the source thereofmore » on Earth, or could have triggered the chirality that was ultimately achieved for Earth's amino acids.« less

Amino acids in the cultivation of mammalian cells.

PubMed

Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

2016-05-01

Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure.

Theoretical Studies of Interactions between O-Phosphorylated and Standard Amino-Acid Side-Chain Models in Water

PubMed Central

Wiśniewska, Marta; Sobolewski, Emil; Ołdziej, Stanisław; Liwo, Adam; Scheraga, Harold A.; Makowski, Mariusz

2015-01-01

Phosphorylation is a common post-translational modification of the amino-acid side chains (serine, tyrosine, and threonine) that contain hydroxyl groups. The transfer of the negatively charged phosphate group from an ATP molecule to such amino-acid side chains leads to changes in the local conformations of proteins and the pattern of interactions with other amino-acid side-chains. A convenient characteristic of the side chain–side chain interactions in the context of an aqueous environment is the potential of mean force (PMF) in water. A series of umbrella-sampling molecular dynamic (MD) simulations with the AMBER force field were carried out for pairs of O-phosphorylated serine (pSer), threonine (pThr), and tyrosine, (pTyr) with natural amino acids in a TIP3P water model as a solvent at 298 K. The weighted-histogram analysis method was used to calculate the four-dimensional potentials of mean force. The results demonstrate that the positions and depths of the contact minima and the positions and heights of the desolvation maxima, including their dependence on the relative orientation depend on the character of the interacting pairs. More distinct minima are observed for oppositely charged pairs such as, e.g., O-phosphorylated side-chains and positively charged ones, such as the side-chains of lysine and arginine. PMID:26100791

Adsorption of amino acids by fullerenes and fullerene nanowhiskers

NASA Astrophysics Data System (ADS)

Hashizume, Hideo; Hirata, Chika; Fujii, Kazuko; Miyazawa, Kun'ichi

2015-12-01

We have investigated the adsorption of some amino acids and an oligopeptide by fullerene (C60) and fullerene nanowhiskers (FNWs). C60 and FNWs hardly adsorbed amino acids. Most of the amino acids used have a hydrophobic side chain. Ala and Val, with an alkyl chain, were not adsorbed by the C60 or FNWs. Trp, Phe and Pro, with a cyclic structure, were not adsorbed by them either. The aromatic group of C60 did not interact with the side chain. The carboxyl or amino group, with the frame structure of an amino acid, has a positive or negative charge in solution. It is likely that the C60 and FNWs would not prefer the charged carboxyl or amino group. Tri-Ala was adsorbed slightly by the C60 and FNWs. The carboxyl or amino group is not close to the center of the methyl group of Tri-Ala. One of the methyl groups in Tri-Ala would interact with the aromatic structure of the C60 and FNWs. We compared our results with the theoretical interaction of 20 bio-amino acids with C60. The theoretical simulations showed the bonding distance between C60 and an amino acid and the dissociation energy. The dissociation energy was shown to increase in the order, Val < Phe < Pro < Asp < Ala < Trp < Tyr < Arg < Leu. However, the simulation was not consistent with our experimental results. The adsorption of albumin (a protein) by C60 showed the effect on the side chains of Try and Trp. The structure of albumin was changed a little by C60. In our study Try and Tyr were hardly adsorbed by C60 and FNWs. These amino acids did not show a different adsorption behavior compared with other amino acids. The adsorptive behavior of mono-amino acids might be different from that of polypeptides.

A study on the interactions of amino acids with nitrogen doped graphene; docking, MD simulation, and QM/MM studies.

PubMed

Ghadari, Rahim

2016-02-14

The binding properties of twenty amino acids with nitrogen-doped graphene structures were studied using docking, MD simulation, and QM/MM methods. TDDFT studies were carried out to investigate the change in the electronic properties of the amino acids because of the presence of the solvent and nitrogen-doped graphene. The results revealed that π-π interactions between the amino acids with a benzene moiety and the surface of the graphene are the most important interactions. The observed red shifts in the TDDFT results which were related to the lower LUMO energies and higher HOMO energies are consistent with this statement.

Amino acid substitutions affecting aspartic acid 605 and valine 606 decrease the interaction strength between the influenza virus RNA polymerase PB2 '627' domain and the viral nucleoprotein.

PubMed

Hsia, Ho-Pan; Yang, Yin-Hua; Szeto, Wun-Chung; Nilsson, Benjamin E; Lo, Chun-Yeung; Ng, Andy Ka-Leung; Fodor, Ervin; Shaw, Pang-Chui

2018-01-01

The influenza virus RNA genome is transcribed and replicated in the context of the viral ribonucleoprotein (vRNP) complex by the viral RNA polymerase. The nucleoprotein (NP) is the structural component of the vRNP providing a scaffold for the viral RNA. In the vRNP as well as during transcription and replication the viral polymerase interacts with NP but it is unclear which parts of the polymerase and NP mediate these interactions. Previously the C-terminal '627' domain (amino acids 538-693) of PB2 was shown to interact with NP. Here we report that a fragment encompassing amino acids 146-185 of NP is sufficient to mediate this interaction. Using NMR chemical shift perturbation assays we show that amino acid region 601 to 607 of the PB2 '627' domain interacts with this fragment of NP. Substitutions of these PB2 amino acids resulted in diminished RNP activity and surface plasmon resonance assays showed that amino acids D605 was essential for the interaction with NP and V606 may also play a partial role in the interaction. Collectively these results reveal a possible interaction surface between NP and the PB2 subunit of the RNA polymerase complex.

Amino Acid Availability Modulates Vacuolar H+-ATPase Assembly*

PubMed Central

Stransky, Laura A.; Forgac, Michael

2015-01-01

The vacuolar H+-ATPase (V-ATPase) is an ATP-dependent proton pump composed of a peripheral ATPase domain (V1) and a membrane-integral proton-translocating domain (V0) and is involved in many normal and disease processes. An important mechanism of regulating V-ATPase activity is reversible assembly of the V1 and V0 domains. Increased assembly in mammalian cells occurs under various conditions and has been shown to involve PI3K. The V-ATPase is necessary for amino acid-induced activation of mechanistic target of rapamycin complex 1 (mTORC1), which is important in controlling cell growth in response to nutrient availability and growth signals. The V-ATPase undergoes amino acid-dependent interactions with the Ragulator complex, which is involved in recruitment of mTORC1 to the lysosomal membrane during amino acid sensing. We hypothesized that changes in the V-ATPase/Ragulator interaction might involve amino acid-dependent changes in V-ATPase assembly. To test this, we measured V-ATPase assembly by cell fractionation in HEK293T cells treated with and without amino acids. V-ATPase assembly increases upon amino acid starvation, and this effect is reversed upon readdition of amino acids. Lysosomes from amino acid-starved cells possess greater V-ATPase-dependent proton transport, indicating that assembled pumps are catalytically active. Amino acid-dependent changes in both V-ATPase assembly and activity are independent of PI3K and mTORC1 activity, indicating the involvement of signaling pathways distinct from those implicated previously in controlling assembly. By contrast, lysosomal neutralization blocks the amino acid-dependent change in assembly and reactivation of mTORC1 after amino acid starvation. These results identify an important new stimulus for controlling V-ATPase assembly. PMID:26378229

The basic amino acids in the coiled-coil domain of CIN85 regulate its interaction with c-Cbl and phosphatidic acid during epidermal growth factor receptor (EGFR) endocytosis.

PubMed

Zheng, Xiudan; Zhang, Jing; Liao, Kan

2014-07-08

During EGFR internalization CIN85 bridges EGFR-Cbl complex, endocytic machinery and fusible membrane through the interactions of CIN85 with c-Cbl, endophilins and phosphatidic acid. These protein-protein and protein-lipid interactions are mediated or regulated by the positively charged C-terminal coiled-coil domain of CIN85. However, the details of CIN85-lipid interaction remain unknown. The present study suggested a possible electric interaction between the negative charge of phosphatidic acid and the positive charge of basic amino acids in coiled-coil domain. Mutations of the basic amino acids in the coiled-coil domain, especially K645, K646, R648 and R650, into neutral amino acid alanine completely blocked the interaction of CIN85 with c-Cbl or phosphatidic acid. However, they did not affect CIN85-endophilin interaction. In addition, CIN85 was found to associate with the internalized EGFR endosomes. It interacted with several ESCRT (Endosomal Sorting Complex Required for Transport) component proteins for ESCRT assembly on endosomal membrane. Mutations in the coiled-coil domain (deletion of the coiled-coil domain or point mutations of the basic amino acids) dissociated CIN85 from endosomes. These mutants bound the ESCRT components in cytoplasm to prevent them from assembly on endosomal membrane and inhibited EGFR sorting for degradation. As an adaptor protein, CIN85 interacts with variety of partners through several domains. The positive charges of basic amino acids in the coiled-coil domain are not only involved in the interaction with phosphatidic acid, but also regulate the interaction of CIN85 with c-Cbl. CIN85 also interacts with ESCRT components for protein sorting in endosomes. These CIN85-protein and CIN85-lipid interactions enable CIN85 to link EGFR-Cbl endocytic complex with fusible membrane during EGFR endocytosis and subsequently to facilitate ESCRT formation on endosomal membrane for EGFR sorting and degradation.

Differential Occurrence of Interactions and Interaction Domains in Proteins Containing Homopolymeric Amino Acid Repeats

PubMed Central

Pelassa, Ilaria; Fiumara, Ferdinando

2015-01-01

Homopolymeric amino acids repeats (AARs), which are widespread in proteomes, have often been viewed simply as spacers between protein domains, or even as “junk” sequences with no obvious function but with a potential to cause harm upon expansion as in genetic diseases associated with polyglutamine or polyalanine expansions, including Huntington disease and cleidocranial dysplasia. A growing body of evidence indicates however that at least some AARs can form organized, functional protein structures, and can regulate protein function. In particular, certain AARs can mediate protein-protein interactions, either through homotypic AAR-AAR contacts or through heterotypic contacts with other protein domains. It is still unclear however, whether AARs may have a generalized, proteome-wide role in shaping protein-protein interaction networks. Therefore, we have undertaken here a bioinformatics screening of the human proteome and interactome in search of quantitative evidence of such a role. We first identified the sets of proteins that contain repeats of any one of the 20 amino acids, as well as control sets of proteins chosen at random in the proteome. We then analyzed the connectivity between the proteins of the AAR-containing protein sets and we compared it with that observed in the corresponding control networks. We find evidence for different degrees of connectivity in the different AAR-containing protein networks. Indeed, networks of proteins containing polyglutamine, polyglutamate, polyproline, and other AARs show significantly increased levels of connectivity, whereas networks containing polyleucine and other hydrophobic repeats show lower degrees of connectivity. Furthermore, we observed that numerous protein-protein, -nucleic acid, and -lipid interaction domains are significantly enriched in specific AAR protein groups. These findings support the notion of a generalized, combinatorial role of AARs, together with conventional protein interaction domains, in

Reparameterization of Solute—Solute Interactions for Amino Acid-Sugar Systems Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations

PubMed Central

Lay, Wesley K.; Miller, Mark S.

2018-01-01

AMBER/GLYCAM and CHARMM are popular force fields for simulations of amino acids and sugars. Here we report excessively attractive amino acid-sugar interactions in both force fields, and corrections to nonbonded interactions that match experimental osmotic pressures of mixed aqueous solutions of diglycine and sucrose. The modified parameters also improve the ΔGtrans of diglycine from water to aqueous sucrose and, with AMBERff99SB/GLYCAM06, eliminate a caging effect seen in previous simulations of the protein ubiquitin with glucose. PMID:28437100

The basic amino acids in the coiled-coil domain of CIN85 regulate its interaction with c-Cbl and phosphatidic acid during epidermal growth factor receptor (EGFR) endocytosis

PubMed Central

2014-01-01

Background During EGFR internalization CIN85 bridges EGFR-Cbl complex, endocytic machinery and fusible membrane through the interactions of CIN85 with c-Cbl, endophilins and phosphatidic acid. These protein-protein and protein-lipid interactions are mediated or regulated by the positively charged C-terminal coiled-coil domain of CIN85. However, the details of CIN85-lipid interaction remain unknown. The present study suggested a possible electric interaction between the negative charge of phosphatidic acid and the positive charge of basic amino acids in coiled-coil domain. Results Mutations of the basic amino acids in the coiled-coil domain, especially K645, K646, R648 and R650, into neutral amino acid alanine completely blocked the interaction of CIN85 with c-Cbl or phosphatidic acid. However, they did not affect CIN85-endophilin interaction. In addition, CIN85 was found to associate with the internalized EGFR endosomes. It interacted with several ESCRT (Endosomal Sorting Complex Required for Transport) component proteins for ESCRT assembly on endosomal membrane. Mutations in the coiled-coil domain (deletion of the coiled-coil domain or point mutations of the basic amino acids) dissociated CIN85 from endosomes. These mutants bound the ESCRT components in cytoplasm to prevent them from assembly on endosomal membrane and inhibited EGFR sorting for degradation. Conclusions As an adaptor protein, CIN85 interacts with variety of partners through several domains. The positive charges of basic amino acids in the coiled-coil domain are not only involved in the interaction with phosphatidic acid, but also regulate the interaction of CIN85 with c-Cbl. CIN85 also interacts with ESCRT components for protein sorting in endosomes. These CIN85-protein and CIN85-lipid interactions enable CIN85 to link EGFR-Cbl endocytic complex with fusible membrane during EGFR endocytosis and subsequently to facilitate ESCRT formation on endosomal membrane for EGFR sorting and degradation. PMID

Amino acids

MedlinePlus

... this page: //medlineplus.gov/ency/article/002222.htm Amino acids To use the sharing features on this page, please enable JavaScript. Amino acids are organic compounds that combine to form proteins . ...

Amino acid analysis

NASA Technical Reports Server (NTRS)

Winitz, M.; Graff, J. (Inventor)

1974-01-01

The process and apparatus for qualitative and quantitative analysis of the amino acid content of a biological sample are presented. The sample is deposited on a cation exchange resin and then is washed with suitable solvents. The amino acids and various cations and organic material with a basic function remain on the resin. The resin is eluted with an acid eluant, and the eluate containing the amino acids is transferred to a reaction vessel where the eluant is removed. Final analysis of the purified acylated amino acid esters is accomplished by gas-liquid chromatographic techniques.

Amino Acid Chiral Selection Via Weak Interactions in Stellar Environments: Implications for the Origin of Life.

PubMed

Famiano, Michael A; Boyd, Richard N; Kajino, Toshitaka; Onaka, Takashi; Mo, Yirong

2018-06-11

Magnetochiral phenomena may be responsible for the selection of chiral states of biomolecules in meteoric environments. For example, the Supernova Amino Acid Processing (SNAAP) Model was proposed previously as a possible mode of magnetochiral selection of amino acids by way of the weak interaction in strong magnetic fields. In earlier work, this model was shown to produce an enantiomeric excess (ee) as high as 0.014% for alanine. In this paper we present the results of molecular quantum chemistry calculations from which ees are determined for the α-amino acids plus isovaline and norvaline, which were found to have positive ees in meteorites. Calculations are performed for both isolated and aqueous states. In some cases, the aqueous state was found to produce larger ees reaching values as high as a few percent under plausible conditions.

Complexes of polyadenylic acid and the methyl esters of amino acids

NASA Technical Reports Server (NTRS)

Khaled, M. A.; Mulins, D. W., Jr.; Swindle, M.; Lacey, J. C., Jr.

1983-01-01

A study of amino acid methyl esters binding to polyadenylic acid supports the theory that the genetic code originated through weak but selective affinities between amino acids and nucleotides. NMR, insoluble complex analysis, and ultraviolet spectroscopy are used to illustrate a correlation between the hydrophybicities of A amino acids and their binding constants, which, beginning with the largest, are in the order of Phe (having nominally a hydrophobic AAA anticodon), Ile, Leu, Val and Gly (having a hydrophilic anticodon with no A). In general, the binding constants are twice the values by Reuben and Polk (1980) for monomeric AMP, which suggests that polymer amino acids are interacting with only one base. No real differences are found betwen poly A binding for free Phe, Phe methyl ester or Phe amide, except that the amide value is slightly lower.

Genetic and biochemical analysis of the interaction of Bacillus subtilis CodY with branched-chain amino acids.

PubMed

Villapakkam, Anuradha C; Handke, Luke D; Belitsky, Boris R; Levdikov, Vladimir M; Wilkinson, Anthony J; Sonenshein, Abraham L

2009-11-01

Bacillus subtilis CodY protein is a DNA-binding global transcriptional regulator that responds to branched-chain amino acids (isoleucine, leucine, and valine) and GTP. Crystal structure studies have shown that the N-terminal region of the protein includes a GAF domain that contains a hydrophobic pocket within which isoleucine and valine bind. This region is well conserved in CodY homologs. Site-directed mutagenesis was employed to understand the roles of some of the residues in the GAF domain and hydrophobic pocket in interaction with isoleucine and GTP. The F40A, F71E, and F98A forms of CodY were inactive in vivo. They were activatable by GTP but to a much lesser extent by branched-chain amino acids in vitro. The CodY mutant R61A retained partial repression of target promoters in vivo and was able to respond to GTP in vitro but also responded poorly to branched-chain amino acids in vitro unless GTP was simultaneously present. Thus, the GAF domain includes residues essential for full activation of CodY by branched-chain amino acids, but these residues are not critical for activation by GTP. Binding studies with branched-chain amino acids and their analogs revealed that an amino group at position 2 and a methyl group at position 3 of valine are critical components of the recognition of the amino acids by CodY.

D-amino acids inhibit initial bacterial adhesion: thermodynamic evidence.

PubMed

Xing, Su-Fang; Sun, Xue-Fei; Taylor, Alicia A; Walker, Sharon L; Wang, Yi-Fu; Wang, Shu-Guang

2015-04-01

Bacterial biofilms are structured communities of cells enclosed in a self-produced hydrated polymeric matrix that can adhere to inert or living surfaces. D-Amino acids were previously identified as self-produced compounds that mediate biofilm disassembly by causing the release of the protein component of the polymeric matrix. However, whether exogenous D-amino acids could inhibit initial bacterial adhesion is still unknown. Here, the effect of the exogenous amino acid D-tyrosine on initial bacterial adhesion was determined by combined use of chemical analysis, force spectroscopic measurement, and theoretical predictions. The surface thermodynamic theory demonstrated that the total interaction energy increased with more D-tyrosine, and the contribution of Lewis acid-base interactions relative to the change in the total interaction energy was much greater than the overall nonspecific interactions. Finally, atomic force microscopy analysis implied that the hydrogen bond numbers and adhesion forces decreased with the increase in D-tyrosine concentrations. D-Tyrosine contributed to the repulsive nature of the cell and ultimately led to the inhibition of bacterial adhesion. This study provides a new way to regulate biofilm formation by manipulating the contents of D-amino acids in natural or engineered systems. © 2014 Wiley Periodicals, Inc.

Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations.

PubMed

Andrews, Casey T; Campbell, Brady A; Elcock, Adrian H

2017-04-11

Given the ubiquitous nature of protein-DNA interactions, it is important to understand the interaction thermodynamics of individual amino acid side chains for DNA. One way to assess these preferences is to perform molecular dynamics (MD) simulations. Here we report MD simulations of 20 amino acid side chain analogs interacting simultaneously with both a 70-base-pair double-stranded DNA and with a 70-nucleotide single-stranded DNA. The relative preferences of the amino acid side chains for dsDNA and ssDNA match well with values deduced from crystallographic analyses of protein-DNA complexes. The estimated apparent free energies of interaction for ssDNA, on the other hand, correlate well with previous simulation values reported for interactions with isolated nucleobases, and with experimental values reported for interactions with guanosine. Comparisons of the interactions with dsDNA and ssDNA indicate that, with the exception of the positively charged side chains, all types of amino acid side chain interact more favorably with ssDNA, with intercalation of aromatic and aliphatic side chains being especially notable. Analysis of the data on a base-by-base basis indicates that positively charged side chains, as well as sodium ions, preferentially bind to cytosine in ssDNA, and that negatively charged side chains, and chloride ions, preferentially bind to guanine in ssDNA. These latter observations provide a novel explanation for the lower salt dependence of DNA duplex stability in GC-rich sequences relative to AT-rich sequences.

Relative Amino Acid Composition Signatures of Organisms and Environments

PubMed Central

Moura, Alexandra; Savageau, Michael A.; Alves, Rui

2013-01-01

Background Identifying organism-environment interactions at the molecular level is crucial to understanding how organisms adapt to and change the chemical and molecular landscape of their habitats. In this work we investigated whether relative amino acid compositions could be used as a molecular signature of an environment and whether such a signature could also be observed at the level of the cellular amino acid composition of the microorganisms that inhabit that environment. Methodologies/Principal Findings To address these questions we collected and analyzed environmental amino acid determinations from the literature, and estimated from complete genomic sequences the global relative amino acid abundances of organisms that are cognate to the different types of environment. Environmental relative amino acid abundances clustered into broad groups (ocean waters, host-associated environments, grass land environments, sandy soils and sediments, and forest soils), indicating the presence of amino acid signatures specific for each environment. These signatures correlate to those found in organisms. Nevertheless, relative amino acid abundance of organisms was more influenced by GC content than habitat or phylogeny. Conclusions Our results suggest that relative amino acid composition can be used as a signature of an environment. In addition, we observed that the relative amino acid composition of organisms is not highly determined by environment, reinforcing previous studies that find GC content to be the major factor correlating to amino acid composition in living organisms. PMID:24204807

Relative amino acid composition signatures of organisms and environments.

PubMed

Moura, Alexandra; Savageau, Michael A; Alves, Rui

2013-01-01

Identifying organism-environment interactions at the molecular level is crucial to understanding how organisms adapt to and change the chemical and molecular landscape of their habitats. In this work we investigated whether relative amino acid compositions could be used as a molecular signature of an environment and whether such a signature could also be observed at the level of the cellular amino acid composition of the microorganisms that inhabit that environment. To address these questions we collected and analyzed environmental amino acid determinations from the literature, and estimated from complete genomic sequences the global relative amino acid abundances of organisms that are cognate to the different types of environment. Environmental relative amino acid abundances clustered into broad groups (ocean waters, host-associated environments, grass land environments, sandy soils and sediments, and forest soils), indicating the presence of amino acid signatures specific for each environment. These signatures correlate to those found in organisms. Nevertheless, relative amino acid abundance of organisms was more influenced by GC content than habitat or phylogeny. Our results suggest that relative amino acid composition can be used as a signature of an environment. In addition, we observed that the relative amino acid composition of organisms is not highly determined by environment, reinforcing previous studies that find GC content to be the major factor correlating to amino acid composition in living organisms.

Chirality measures of α-amino acids.

PubMed

Jamróz, Michał H; Rode, Joanna E; Ostrowski, Sławomir; Lipiński, Piotr F J; Dobrowolski, Jan Cz

2012-06-25

To measure molecular chirality, the molecule is treated as a finite set of points in the Euclidean R(3) space supplemented by k properties, p(1)((i)), p(2)((i)), ..., p(k)((i)) assigned to the ith atom, which constitute a point in the Property P(k) space. Chirality measures are described as the distance between a molecule and its mirror image minimized over all its arbitrary orientation-preserving isometries in the R(3) × P(k) Cartesian product space. Following this formalism, different chirality measures can be estimated by taking into consideration different sets of atomic properties. Here, for α-amino acid zwitterionic structures taken from the Cambridge Structural Database and for all 1684 neutral conformers of 19 biogenic α-amino acid molecules, except glycine and cystine, found at the B3LYP/6-31G** level, chirality measures have been calculated by a CHIMEA program written in this project. It is demonstrated that there is a significant correlation between the measures determined for the α-amino acid zwitterions in crystals and the neutral forms in the gas phase. Performance of the studied chirality measures with changes of the basis set and computation method was also checked. An exemplary quantitative structure–activity relationship (QSAR) application of the chirality measures was presented by an introductory model for the benchmark Cramer data set of steroidal ligands of the sex-hormone binding globulin.

Formation of specific amino acid sequences during carbodiimide-mediated condensation of amino acids in aqueous solution, and computer-simulated sequence generation

NASA Astrophysics Data System (ADS)

Hartmann, Jürgen; Nawroth, Thomas; Dose, Klaus

1984-12-01

Carbodiimide-mediated peptide synthesis in aqueous solution has been studied with respect to self-ordering of amino acids. The copolymerisation of amino acids in the presence of glutamic acid or pyroglutamic acid leads to short pyroglutamyl peptides. Without pyroglutamic acid the formation of higher polymers is favoured. The interactions of the amino acids and the peptides, however, are very complex. Therefore, the experimental results are rather difficult to explain. Some of the experimental results, however, can be explained with the aid of computer simulation programs. Regarding only the tripeptide fraction the copolymerisation of pyroGlu, Ala and Leu, as well as the simulated copolymerisation lead to pyroGlu-Ala-Leu as the main reaction product. The amino acid composition of the insoluble peptides formed during the copolymerisation of Ser, Gly, Ala, Val, Phe, Leu and Ile corresponds in part to the computer-simulated copolymerisation data.

Racemic resolution of some DL-amino acids using Aspergillus fumigatus L-amino acid oxidase.

PubMed

Singh, Susmita; Gogoi, Binod K; Bezbaruah, Rajib L

2011-07-01

The ability of Aspergillus fumigatus L-amino acid oxidase (L-aao) to cause the resolution of racemic mixtures of DL-amino acids was investigated with DL-alanine, DL-phenylalanine, DL-tyrosine, and DL-aspartic acid. A chiral column, Crownpak CR+ was used for the analysis of the amino acids. The enzyme was able to cause the resolution of the three DL-amino acids resulting in the production of optically pure D-alanine (100% resolution), D-phenylalanine (80.2%), and D-tyrosine (84.1%), respectively. The optically pure D-amino acids have many uses and thus can be exploited industrially. This is the first report of the use of A. fumigatus L: -amino acid oxidase for racemic resolution of DL-amino acids.

UNSATURATED AMINO ACIDS V.

PubMed Central

Shapira, Jacob; Dittmer, Karl

1961-01-01

Shapira, Jacob (Department of Chemistry, Florida State University, Tallahassee) and Karl Dittmer. Unsaturated amino acids. V. Microbiological properties of some halogenated olefinic amino acids. J. Bacteriol. 82:640–647. 1961.—It has been shown previously that several amino acid analogues containing unsaturated linkages were inhibitors of the growth of Escherichia coli and Saccharomyces cerevisiae. This paper reports the results obtained when a series of unsaturated halogen-containing amino acids was examined. The cis isomer of ω-chloroallylglycine showed the greatest toxicity yet found in this series of unsaturated amino acids toward E. coli, whereas the trans-isomer was usually far less toxic. The major effect of cis-ω-chloroallylglycine in E. coli appeared to be to extend the lag phase before the normal rate of growth began. A wide variety of amino acids was capable of partially or completely preventing the toxicity of low levels of these compounds. At higher levels, relatively few amino acids (primarily valine, leucine, and glutamic acid) were effective. In E. coli, cis-ω-chloroallylglycine showed an unusual [Formula: see text] relationship with both glutamic acid and valine over a wide range in concentration. PMID:13911278

A molecular rotor based ratiometric sensor for basic amino acids

NASA Astrophysics Data System (ADS)

Pettiwala, Aafrin M.; Singh, Prabhat K.

2018-01-01

The inevitable importance of basic amino acids, arginine and lysine, in human health and metabolism demands construction of efficient sensor systems for them. However, there are only limited reports on the 'ratiometric' detection of basic amino acids which is further restricted by the use of chemically complex sensor molecules, which impedes their prospect for practical applications. Herein, we report a ratiometric sensor system build on simple mechanism of disassociation of novel emissive Thioflavin-T H-aggregates from heparin surface, when subjected to interaction with basic amino acids. The strong and selective electrostatic and hydrogen bonding interaction of basic amino acids with heparin leads to large alteration in photophysical attributes of heparin bound Thioflavin-T, which forms a highly sensitive sensor platform for detection of basic amino acids in aqueous solution. These selective interactions between basic amino acids and heparin allow our sensor system to discriminate arginine and lysine from other amino acids. This unique mechanism of dissociation of Thioflavin-T aggregates from heparin surface provides ratiometric response on both fluorimetric and colorimetric outputs for detection of arginine and lysine, and thus it holds a significant advantage over other developed sensor systems which are restricted to single wavelength detection. Apart from the sensitivity and selectivity, our system also provides the advantage of simplicity, dual mode of sensing, and more importantly, it employs an inexpensive commercially available probe molecule, which is a significant advantage over other developed sensor systems that uses tedious synthesis protocol for the employed probe in the detection scheme, an impediment for practical applications. Additionally, our sensor system also shows response in complex biological media of serum samples.

A molecular rotor based ratiometric sensor for basic amino acids.

PubMed

Pettiwala, Aafrin M; Singh, Prabhat K

2018-01-05

The inevitable importance of basic amino acids, arginine and lysine, in human health and metabolism demands construction of efficient sensor systems for them. However, there are only limited reports on the 'ratiometric' detection of basic amino acids which is further restricted by the use of chemically complex sensor molecules, which impedes their prospect for practical applications. Herein, we report a ratiometric sensor system build on simple mechanism of disassociation of novel emissive Thioflavin-T H-aggregates from heparin surface, when subjected to interaction with basic amino acids. The strong and selective electrostatic and hydrogen bonding interaction of basic amino acids with heparin leads to large alteration in photophysical attributes of heparin bound Thioflavin-T, which forms a highly sensitive sensor platform for detection of basic amino acids in aqueous solution. These selective interactions between basic amino acids and heparin allow our sensor system to discriminate arginine and lysine from other amino acids. This unique mechanism of dissociation of Thioflavin-T aggregates from heparin surface provides ratiometric response on both fluorimetric and colorimetric outputs for detection of arginine and lysine, and thus it holds a significant advantage over other developed sensor systems which are restricted to single wavelength detection. Apart from the sensitivity and selectivity, our system also provides the advantage of simplicity, dual mode of sensing, and more importantly, it employs an inexpensive commercially available probe molecule, which is a significant advantage over other developed sensor systems that uses tedious synthesis protocol for the employed probe in the detection scheme, an impediment for practical applications. Additionally, our sensor system also shows response in complex biological media of serum samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Transport of amino acids in the kidney.

PubMed

Makrides, Victoria; Camargo, Simone M R; Verrey, François

2014-01-01

Amino acids are the building blocks of proteins and key intermediates in the synthesis of biologically important molecules, as well as energy sources, neurotransmitters, regulators of cellular metabolism, etc. The efficient recovery of amino acids from the primary filtrate is a well-conserved key role of the kidney proximal tubule. Additionally, renal metabolism participates in the whole body disposition of amino acids. Therefore, a wide array of axially heterogeneously expressed transporters is localized on both epithelial membranes. For transepithelial transport, luminal uptake, which is carried out mainly by active symporters, is coupled with a mostly passive basolateral efflux. Many transporters require partner proteins for appropriate localization, or to modulate transporter activity, and/or increase substrate supply. Interacting proteins include cell surface antigens (CD98), endoplasmic reticulum proteins (GTRAP3-18 or 41), or enzymes (ACE2 and aminopeptidase N). In the past two decades, the molecular identification of transporters has led to significant advances in our understanding of amino acid transport and aminoacidurias arising from defects in renal transport. Furthermore, the three-dimensional crystal structures of bacterial homologues have been used to yield new insights on the structure and function of mammalian transporters. Additionally, transgenic animal models have contributed to our understanding of the role of amino acid transporters in the kidney and other organs and/or at critical developmental stages. Progress in elucidation of the renal contribution to systemic amino acid homeostasis requires further integration of kinetic, regulatory, and expression data of amino acid transporters into our understanding of physiological regulatory networks controlling metabolism. © 2014 American Physiological Society.

A coarse-grained model of the effective interaction for charged amino acid residues and its application to formation of GCN4-pLI tetramer

NASA Astrophysics Data System (ADS)

Kawaguchi, Kazutomo; Nakagawa, Satoshi; Kurniawan, Isman; Kodama, Koichi; Arwansyah, Muhammad Saleh; Nagao, Hidemi

2018-03-01

We present a simple coarse-grained model of the effective interaction for charged amino acid residues, such as Glu and Lys, in a water solvent. The free-energy profile as a function of the distance between two charged amino acid side-chain analogues in an explicit water solvent is calculated with all-atom molecular dynamics simulation and thermodynamic integration method. The calculated free-energy profile is applied to the coarse-grained potential of the effective interaction between two amino acid residues. The Langevin dynamics simulations with our coarse-grained potential are performed for association of a small protein complex, GCN4-pLI tetramer. The tetramer conformation reproduced by our coarse-grained model is similar to the X-ray crystallographic structure. We show that the effective interaction between charged amino acid residues stabilises association and orientation of protein complex. We also investigate the association pathways of GCN4-pLI tetramer.

Microbial degradation of poly(amino acid)s.

PubMed

Obst, Martin; Steinbüchel, Alexander

2004-01-01

Natural poly(amino acid)s are a group of poly(ionic) molecules (ionomers) with various biological functions and putative technical applications and play, therefore, an important role both in nature and in human life. Because of their biocompatibility and their synthesis from renewable resources, poly(amino acid)s may be employed for many different purposes covering a broad spectrum of medical, pharmaceutical, and personal care applications as well as the domains of agriculture and of environmental applications. Biodegradability is one important advantage of naturally occurring poly(amino acid)s over many synthetic polymers. The intention of this review is to give an overview about the enzyme systems catalyzing the initial steps in poly(amino acid) degradation. The focus is on the naturally occurring poly(amino acid)s cyanophycin, poly(epsilon-L-lysine) and poly(gamma-glutamic acid); but biodegradation of structurally related synthetic polyamides such as poly(aspartic acid) and nylons, which are known from various technical applications, is also included.

The impacts of temperature, alcoholic degree and amino acids content on biogenic amines and their precursor amino acids content in red wine.

PubMed

Lorenzo, C; Bordiga, M; Pérez-Álvarez, E P; Travaglia, F; Arlorio, M; Salinas, M R; Coïsson, J D; Garde-Cerdán, T

2017-09-01

The aim was to study how factors such as temperature, alcoholic degree, and amino acids supplementation are able to influence the content of tyramine, histamine, 2-phenylethylamine, tryptamine and their precursor amino acids in winemaking process. Biogenic amines and amino acids were quantified at the beginning, middle and end of alcoholic fermentation, and at the end of malolactic fermentation. In general, samples produced with amino acid supplementation did not show the highest concentrations of biogenic amines, except for histamine, which content increased with the addition of the four amino acids. The synthesis of tyramine was mainly affected by the temperature and alcoholic degree, the formation of phenylethylamine was largely influenced by alcoholic degree, and tryptamine synthesis principally depended on temperature. Interestingly, there was interaction between these three factors for the biogenic amines studied. In conclusion, winemaking conditions should be established depending on the biogenic amine which synthesis is required to be controlled. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanisms of volatile production from non-sulfur amino acids by irradiation

NASA Astrophysics Data System (ADS)

Ahn, Dong Uk; Lee, Eun Joo; Feng, Xi; Zhang, Wangang; Lee, Ji Hwan; Jo, Cheorun; Nam, Kichang

2016-02-01

Non-sulfur amino acid monomers were used to study the mechanisms of volatile production in meat by irradiation. Irradiation not only produced many volatiles but also increased the amounts of volatiles from non-sulfur amino acid monomers. The major reaction mechanisms involved in volatile production from each group of the amino acids by irradiation differ significantly. However, we speculate that the radiolysis of amino acid side chains were the major mechanism. In addition, Strecker degradation, especially the production of aldehydes from aliphatic group amino acids, and deamination, isomerization, decarboxylation, cyclic reaction and dehydrogenation of the initial radiolytic products were also contributed to the production of volatile compounds. Each amino acid monomers produced different odor characteristics, but the intensities of odor from all non-sulfur amino acid groups were very weak. This indicated that the contribution of volatiles produced from non-sulfur amino acids was minor. If the volatile compounds from non-sulfur amino acids, especially aldehydes, interact with other volatiles compounds such as sulfur compounds, however, they can contribute to the off-odor of irradiated meat significantly.

Formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations - A review.

PubMed

Zhao, Cindy J; Schieber, Andreas; Gänzle, Michael G

2016-11-01

Fermented foods are valued for their rich and complex odour and taste. The metabolic activity of food-fermenting microorganisms determines food quality and generates odour and taste compounds. This communication reviews the formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations. Pathways of the generation of taste compounds are presented for soy sauce, cheese, fermented meats, and bread. Proteolysis or autolysis during food fermentations generates taste-active amino acids and peptides; peptides derived from proteolysis particularly impart umami taste (e.g. α-glutamyl peptides) or bitter taste (e.g. hydrophobic peptides containing proline). Taste active peptide derivatives include pyroglutamyl peptides, γ-glutamyl peptides, and succinyl- or lactoyl amino acids. The influence of fermentation microbiota on proteolysis, and peptide hydrolysis, and the metabolism of glutamate and arginine is well understood, however, the understanding of microbial metabolic activities related to the formation of taste-active peptide derivatives is incomplete. Improved knowledge of the interactions between taste-active compounds will enable the development of novel fermentation strategies to develop tastier, less bitter, and low-salt food products, and may provide novel and "clean label" ingredients to improve the taste of other food products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulation of Intestinal Mucosal Growth by Amino Acids

PubMed Central

Ray, Ramesh M.; Johnson, Leonard R.

2013-01-01

Amino acids, especially glutamine (GLN) have been known for many years to stimulate the growth of small intestinal mucosa. Polyamines are also required for optimal mucosal growth, and the inhibition of ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis, blocks growth. Certain amino acids, primarily asparagine (ASN) and GLN stimulate ODC activity in a solution of physiological salts. More importantly, their presence is also required before growth factors and hormones such as EGF and insulin are able to increase ODC activity. ODC activity is inhibited by antizyme-1 (AZ) whose synthesis is stimulated by polyamines, thus, providing a negative feedback regulation of the enzyme. In the absence of amino acids mammalian target of rapamycin complex 1 (mTORC1) is inhibited, whereas, mTORC2 is stimulated leading to the inhibition of global protein synthesis but increasing the synthesis of AZ via a cap-independent mechanism. These data, therefore, explain why ASN or GLN is essential for the activation of ODC. Interestingly, in a number of papers, AZ has been shown to inhibit cell proliferation, stimulate apoptosis or increase autophagy. Each of these activities results in decreased cellular growth. AZ binds to and accelerates the degradation of ODC and other proteins shown to regulate proliferation and cell death, such as Aurora-A, Cyclin D1 and Smad1. The correlation between the stimulation of ODC activity and the absence of AZ as influenced by amino acids is high. Not only do amino acids such as ASN and GLN stimulate ODC while inhibiting AZ synthesis, but also amino acids such as lysine, valine and ornithine, which inhibit ODC activity, increase the synthesis of AZ. The question remaining to be answered is whether AZ inhibits growth directly or whether it acts by decreasing the availability of polyamines to the dividing cells. In either case, evidence strongly suggests that the regulation of AZ synthesis is the mechanism through which amino

Regulation of intestinal mucosal growth by amino acids.

PubMed

Ray, Ramesh M; Johnson, Leonard R

2014-03-01

Amino acids, especially glutamine (GLN) have been known for many years to stimulate the growth of small intestinal mucosa. Polyamines are also required for optimal mucosal growth, and the inhibition of ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis, blocks growth. Certain amino acids, primarily asparagine (ASN) and GLN stimulate ODC activity in a solution of physiological salts. More importantly, their presence is also required before growth factors and hormones such as epidermal growth factor and insulin are able to increase ODC activity. ODC activity is inhibited by antizyme-1 (AZ) whose synthesis is stimulated by polyamines, thus, providing a negative feedback regulation of the enzyme. In the absence of amino acids mammalian target of rapamycin complex 1 (mTORC1) is inhibited, whereas, mTORC2 is stimulated leading to the inhibition of global protein synthesis but increasing the synthesis of AZ via a cap-independent mechanism. These data, therefore, explain why ASN or GLN is essential for the activation of ODC. Interestingly, in a number of papers, AZ has been shown to inhibit cell proliferation, stimulate apoptosis, or increase autophagy. Each of these activities results in decreased cellular growth. AZ binds to and accelerates the degradation of ODC and other proteins shown to regulate proliferation and cell death, such as Aurora-A, Cyclin D1, and Smad1. The correlation between the stimulation of ODC activity and the absence of AZ as influenced by amino acids is high. Not only do amino acids such as ASN and GLN stimulate ODC while inhibiting AZ synthesis, but also amino acids such as lysine, valine, and ornithine, which inhibit ODC activity, increase the synthesis of AZ. The question remaining to be answered is whether AZ inhibits growth directly or whether it acts by decreasing the availability of polyamines to the dividing cells. In either case, evidence strongly suggests that the regulation of AZ synthesis is the

Fmoc/Trt-amino acids: comparison to Fmoc/tBu-amino acids in peptide synthesis.

PubMed

Barlos, K; Gatos, D; Koutsogianni, S

1998-03-01

Model peptides containing the nucleophilic amino acids Trp and Met have been synthesized with the application of Fmoc/Trt- and Fmoc/tBu-amino acids, for comparison. The deprotection of the peptides synthesized using Fmoc/Trt-amino acids in all cases leads to crude peptides of higher purity than that of the same peptides synthesized using Fmoc/tBu-amino acids.

The Use of Gel Electrophoresis to Study the Reactions of Activated Amino Acids with Oligonucleotides

NASA Technical Reports Server (NTRS)

Zieboll, Gerhard; Orgel, Leslie E.

1994-01-01

We have used gel electrophoresis to study the primary covalent addition of amino acids to oligonu-cleotides or their analogs and the subsequent addition of further molecules of the amino acids to generate peptides covalently linked to the oligonucleotides. We have surveyed the reactions of a variety of amino acids with the phosphoramidates derived from oligonucleotide 5 inches phosphates and ethylenediamine. We find that arginine and amino acids can interact with oligonucleotidesl through stacking interactions react most efficiently. D- and L-amino acids give indistinguishable families of products.

Both dietary supplementation with monosodium L-glutamate and fat modify circulating and tissue amino acid pools in growing pigs, but with little interactive effect.

PubMed

Feng, Zemeng; Zhou, Xiaoli; Wu, Fei; Yao, Kang; Kong, Xiangfeng; Li, Tiejun; Blachier, Francois; Yin, Yulong

2014-01-01

The Chinese population has undergone rapid transition to a high-fat diet. Furthermore, monosodium L-glutamate (MSG) is widely used as a daily food additive in China. Little information is available on the effects of oral MSG and dietary fat supplementation on the amino acid balance in tissues. The present study aimed to determine the effects of both dietary fat and MSG on amino acid metabolism in growing pigs, and to assess any possible interactions between these two nutrients. Four iso-nitrogenous and iso-caloric diets (basal diet, high fat diet, basal diet with 3% MSG and high fat diet with 3% MSG) were provided to growing pigs. The dietary supplementation with fat and MSG used alone and in combination were found to modify circulating and tissue amino acid pools in growing pigs. Both dietary fat and MSG modified the expression of gene related to amino acid transport in jejunum. Both dietary fat and MSG clearly influenced amino acid content in tissues but in different ways. Both dietary fat and MSG enhance the absorption of amino acids in jejunum. However, there was little interaction between the effects of dietary fat and MSG.

Both Dietary Supplementation with Monosodium L-Glutamate and Fat Modify Circulating and Tissue Amino Acid Pools in Growing Pigs, but with Little Interactive Effect

PubMed Central

Feng, Zemeng; Zhou, Xiaoli; Wu, Fei; Yao, Kang; Kong, Xiangfeng; Li, Tiejun; Blachier, Francois; Yin, Yulong

2014-01-01

Background The Chinese population has undergone rapid transition to a high-fat diet. Furthermore, monosodium L-glutamate (MSG) is widely used as a daily food additive in China. Little information is available on the effects of oral MSG and dietary fat supplementation on the amino acid balance in tissues. The present study aimed to determine the effects of both dietary fat and MSG on amino acid metabolism in growing pigs, and to assess any possible interactions between these two nutrients. Methods and Results Four iso-nitrogenous and iso-caloric diets (basal diet, high fat diet, basal diet with 3% MSG and high fat diet with 3% MSG) were provided to growing pigs. The dietary supplementation with fat and MSG used alone and in combination were found to modify circulating and tissue amino acid pools in growing pigs. Both dietary fat and MSG modified the expression of gene related to amino acid transport in jejunum. Conclusions Both dietary fat and MSG clearly influenced amino acid content in tissues but in different ways. Both dietary fat and MSG enhance the absorption of amino acids in jejunum. However, there was little interaction between the effects of dietary fat and MSG. PMID:24465415

Fluorescence properties of 3-amino phenylboronic acid and its interaction with glucose and ZnS:Cu quantum dots.

PubMed

Kur-Kowalska, Karolina; Przybyt, Małgorzata; Ziółczyk, Paulina; Sowiński, Przemysław; Miller, Ewa

2014-08-14

Preliminary results of a study of the interaction between 3-amino phenylboronic acid and glucose or ZnS:Cu quantum dots are presented in this paper. ZnS:Cu quantum dots with mercaptopropionic acid as a capping agent were obtained and characterized. Quenching of 3-amino phenylboronic acid fluorescence was studied by steady-state and timeresolved measurements. For fluorescence quenching with glucose the results of steady-state measurements fulfill Stern-Volmer equation. The quenching constants are increasing with growing pH. The decay of fluorescence is monoexponential with lifetime about 8.4 ns, which does not depend on pH and glucose concentration indicating static quenching. The quenching constant can be interpreted as apparent equilibrium constant of estrification of boronic group with diol. Quantum dots are also quenching 3-amino phenylboronic acid fluorescence. Fluorescence lifetime, in this case, is slightly decreasing with increasing concentration of quantum dots. The quenching constants are increasing slightly with pH's growth. Quenching mechanism of 3-amino phenylboronic acid fluorescence by quantum dots needs further experiments to be fully explained. Copyright © 2014 Elsevier B.V. All rights reserved.

α-Amino Acid-Isosteric α-Amino Tetrazoles

PubMed Central

Zhao, Ting; Kurpiewska, Katarzyna; Kalinowska-Tłuścik, Justyna; Herdtweck, Eberhardt

2016-01-01

The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field. PMID:26817531

d-Amino acids in molecular evolution in space - Absolute asymmetric photolysis and synthesis of amino acids by circularly polarized light.

PubMed

Sugahara, Haruna; Meinert, Cornelia; Nahon, Laurent; Jones, Nykola C; Hoffmann, Søren V; Hamase, Kenji; Takano, Yoshinori; Meierhenrich, Uwe J

2018-07-01

Living organisms on the Earth almost exclusively use l-amino acids for the molecular architecture of proteins. The biological occurrence of d-amino acids is rare, although their functions in various organisms are being gradually understood. A possible explanation for the origin of biomolecular homochirality is the delivery of enantioenriched molecules via extraterrestrial bodies, such as asteroids and comets on early Earth. For the asymmetric formation of amino acids and their precursor molecules in interstellar environments, the interaction with circularly polarized photons is considered to have played a potential role in causing chiral asymmetry. In this review, we summarize recent progress in the investigation of chirality transfer from chiral photons to amino acids involving the two major processes of asymmetric photolysis and asymmetric synthesis. We will discuss analytical data on cometary and meteoritic amino acids and their potential impact delivery to the early Earth. The ongoing and future ambitious space missions, Hayabusa2, OSIRIS-REx, ExoMars 2020, and MMX, are scheduled to provide new insights into the chirality of extraterrestrial organic molecules and their potential relation to the terrestrial homochirality. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca. Copyright © 2018 Elsevier B.V. All rights reserved.

Fortifying Horticultural Crops with Essential Amino Acids: A Review.

PubMed

Wang, Guoping; Xu, Mengyun; Wang, Wenyi; Galili, Gad

2017-06-19

To feed the world's growing population, increasing the yield of crops is not the only important factor, improving crop quality is also important, and it presents a significant challenge. Among the important crops, horticultural crops (particularly fruits and vegetables) provide numerous health compounds, such as vitamins, antioxidants, and amino acids. Essential amino acids are those that cannot be produced by the organism and, therefore, must be obtained from diet, particularly from meat, eggs, and milk, as well as a variety of plants. Extensive efforts have been devoted to increasing the levels of essential amino acids in plants. Yet, these efforts have been met with very little success due to the limited genetic resources for plant breeding and because high essential amino acid content is generally accompanied by limited plant growth. With a deep understanding of the biosynthetic pathways of essential amino acids and their interactions with the regulatory networks in plants, it should be possible to use genetic engineering to improve the essential amino acid content of horticultural plants, rendering these plants more nutritionally favorable crops. In the present report, we describe the recent advances in the enhancement of essential amino acids in horticultural plants and possible future directions towards their bio-fortification.

Surface Propensity of Atmospherically Relevant Amino Acids Studied by XPS.

PubMed

Mocellin, Alexandra; Gomes, Anderson Herbert de Abreu; Araújo, Oscar Cardoso; de Brito, Arnaldo Naves; Björneholm, Olle

2017-04-27

Amino acids constitute an important fraction of the water-soluble organic nitrogen (WSON) compounds in aerosols and are involved in many processes in the atmosphere. In this work, we applied X-ray photoelectron spectroscopy (XPS) to study aqueous solutions of four amino acids, glycine, alanine, valine, and methionine, in their zwitterionic forms. We found that amino acids with hydrophilic side chains and smaller size, GLY and ALA, tend to stay in the bulk of the liquid, while the hydrophobic and bigger amino acids, VAL and MET, are found to concentrate more on the surface. We found experimental evidence that the amino acids have preferential orientation relative to the surface, with the hydrophobic side chain being closer to the surface than the hydrophilic carboxylate group. The observed amino acid surface propensity has implications in atmospheric science as the surface interactions play a central role in cloud droplet formation, and they should be considered in climate models.

New Enzymatic Method of Chiral Amino Acid Synthesis by Dynamic Kinetic Resolution of Amino Acid Amides: Use of Stereoselective Amino Acid Amidases in the Presence of α-Amino-ɛ-Caprolactam Racemase▿

PubMed Central

Yamaguchi, Shigenori; Komeda, Hidenobu; Asano, Yasuhisa

2007-01-01

d- and l-amino acids were produced from l- and d-amino acid amides by d-aminopeptidase from Ochrobactrum anthropi C1-38 and l-amino acid amidase from Pseudomonas azotoformans IAM 1603, respectively, in the presence of α-amino-ɛ-caprolactam racemase from Achromobacter obae as the catalyst by dynamic kinetic resolution of amino acid amides. PMID:17586677

Role of Protein and Amino Acids in Infant and Young Child Nutrition: Protein and Amino Acid Needs and Relationship with Child Growth.

PubMed

Uauy, Ricardo; Kurpad, Anura; Tano-Debrah, Kwaku; Otoo, Gloria E; Aaron, Grant A; Toride, Yasuhiko; Ghosh, Shibani

2015-01-01

Over a third of all deaths of children under the age of five are linked to undernutrition. At a 90% coverage level, a core group of ten interventions inclusive of infant and young child nutrition could save one million lives of children under 5 y of age (15% of all deaths) (Lancet 2013). The infant and young child nutrition package alone could save over 220,000 lives in children under 5 y of age. High quality proteins (e.g. milk) in complementary, supplementary and rehabilitation food products have been found to be effective for good growth. Individual amino acids such as lysine and arginine have been found to be factors linked to growth hormone release in young children via the somatotropic axis and high intakes are inversely associated with fat mass index in pre-pubertal lean girls. Protein intake in early life is positively associated with height and weight at 10 y of age. This paper will focus on examining the role of protein and amino acids in infant and young child nutrition by examining protein and amino acid needs in early life and the subsequent relationship with stunting.

Wet, Carbonaceous Asteroids: Altering Minerals, Changing Amino Acids

NASA Astrophysics Data System (ADS)

Taylor, G. J.

2011-04-01

Many carbonaceous chondrites contain alteration products from water-rock interactions at low temperature and organic compounds. A fascinating fact known for decades is the presence in some of them of an assortment of organic compounds, including amino acids, sometimes called the building blocks of life. Murchison and other CM carbonaceous chondrites contain hundreds of amino acids. Early measurements indicated that the amino acids in carbonaceous chondrites had equal proportions of L- and D-structures, a situation called racemic. This was in sharp contrast to life on Earth, which heavily favors L- forms. However, beginning in 1997, John Cronin and Sandra Pizzarello (Arizona State University) found L- excesses in isovaline and several other amino acids in the Murchison carbonaceous chondrite. In 2009, Daniel Glavin and Jason Dworkin (Astrobiology Analytical Lab, Goddard Space Flight Center) reported the first independent confirmation of L-isovaline excesses in Murchison using a different analytical technique than employed by Cronin and Pizzarello. Inspired by this work, Daniel Glavin, Michael Callahan, Jason Dworkin, and Jamie Elsila (Astrobiology Analytical Lab, Goddard Space Flight Center), have done an extensive study of the abundance and symmetry of amino acids in carbonaceous chondrites that experienced a range of alteration by water in their parent asteroids. The results show that amino acids are more abundant in the less altered meteorites, implying that aqueous processing changes the mix of amino acids. They also confirmed the enrichment in L-structures of some amino acids, especially isovaline, confirming earlier work. The authors suggest that aqueously-altered planetesimals might have seeded the early Earth with nonracemic amino acids, perhaps explaining why life from microorganisms to people use only L- forms to make proteins. The initial imbalance caused by non-biologic processes in wet asteroids might have been amplified by life on Earth. Alternatively

Intermolecular Vibrations of Hydrophobic Amino Acids

NASA Astrophysics Data System (ADS)

Williams, Michael Roy Casselman

Hydrophobic amino acids interact with their chemical environment through a combination of electrostatic, hydrogen bonding, dipole, induced dipole, and dispersion forces. These interactions all have their own characteristic energy scale and distance dependence. The low-frequency (0.1-5 THz, 5-150 cm-1) vibrational modes of amino acids in the solid state are a direct indicator of the interactions between the molecules, which include interactions between an amino acid functional group and its surroundings. This information is central to understanding the dynamics and morphology of proteins. The alpha-carbon is a chiral center for all of the hydrophobic amino acids, meaning that they exist in two forms, traditionally referred to as L- and D-enantiomers. This nomenclature indicates which direction the molecule rotates plane-polarized visible light (levorotory and dextrorotory). Chiral a-amino acids in proteins are exclusively the L-variety In the solid state, the crystal lattice of the pure L-enantiomer is the mirror image of the D-enantiomer crystal lattice. These solids are energetically identical. Enantiomers also have identical spectroscopic properties except when the measurement is polarization sensitive. A mixture of equal amounts D- and L-amino acid enantiomers can crystallize into a racemic (DL-) structure that is different from that of the pure enantiomers. Whether a solution of both enantiomers will crystallize into a racemic form or spontaneously resolve into a mixture of separate D- and L-crystals largely depends on the interactions between molecules available in the various possible configurations. This is an active area of research. Low-frequency vibrations with intermolecular character are very sensitive to changes in lattice geometry, and consequently the vibrational spectra of racemic crystals are usually quite distinct from the spectra of the crystals of the corresponding pure enantiomers in the far-infrared (far-IR). THz time-domain spectroscopy (THz

Label-free amino acid detection based on nanocomposites of graphene oxide hybridized with gold nanoparticles.

PubMed

Zhang, Qian; Zhang, Diming; Lu, Yanli; Xu, Gang; Yao, Yao; Li, Shuang; Liu, Qingjun

2016-03-15

Nanocomposites of graphene oxide and gold nanoparticles (GO/GNPs) were synthesized for label-free detections of amino acids. Interactions between the composites and amino acids were investigated by both naked-eye observation and optical absorption spectroscopy. The GO/GNPs composites displayed apparent color changes and absorption spectra changes in presences of amino acids including glutamate, aspartate, and cysteine. The interaction mechanisms of the composites and amino acids were discussed and explored with sulfhydryl groups and non-α-carboxylic groups on the amino acids. Sensing properties of the composites were tested, while pure gold particles were used as the control. The results suggested that the GO/GNPs composites had better linearity and stability in dose-dependent responses to the amino acids than those of the particles, especially in detections for acidic amino acids. Therefore, the nanocomposites platform can provide a convenient and efficient approach for label-free optical detections of important molecules such as amino acids. Copyright © 2015 Elsevier B.V. All rights reserved.

Plasma growth hormone (GH), insulin and amino acid responses to arginine with or without aspartic acid in pigs. Effect of the dose.

PubMed

Cochard, A; Guilhermet, R; Bonneau, M

1998-01-01

The aim of the present study was to examine, for the first time in pigs, the dose-dependent effect of arginine (ARG) on growth hormone (GH) and insulin release and the effect of the combined ARG and aspartic acid (ASP) treatment on GH and insulin release. ARG (0.5 or 1 g/kg body weight) with or without an equimolar supplement of ASP (0.38 or 0.76 g/kg, respectively) was administered in piglets via the duodenum. ARG increased plasma arginine, ornithine, urea, proline and branched chain amino acid concentrations. ASP increased specifically plasma aspartic acid, glutamic acid, alanine and citrulline concentrations. Plasma insulin increased with no apparent difference between treatments. Maximum GH level and the area under the GH curve (AUC) were increased in a dose-dependent manner in response to ARG treatment. GH response to the combined ARG and ASP treatment (ARGASP) was delayed compared to ARG alone and was not dose-dependent. AUC for GH after ARGASP treatments were intermediate between those observed after the two ARG doses. Our data suggest that high ASP doses transiently inhibit and delay ARG-induced GH release in pigs and that an equimolar supplement of ASP stimulates or inhibits ARG-induced GH release depending on the dose used.

Computational Design of Thermostabilizing d-Amino Acid Substitutions

PubMed Central

Rodriguez-Granillo, Agustina; Annavarapu, Srinivas; Zhang, Lei; Koder, Ronald L.; Nanda, Vikas

2012-01-01

Judicious incorporation of d-amino acids in engineered proteins confer many advantages such as preventing degradation by endogenous proteases, and designing novel structures and functions not accessible to homochiral polypeptides. Glycine to d-alanine substitutions at the carboxy-termini can stabilize α-helices by reducing conformational entropy. Beyond alanine, we propose additional side chain effects on the degree of stabilization conferred by d-amino acid substitutions. A detailed, molecular understanding of backbone and side chain interactions is important for developing rational, broadly applicable strategies in using d-amino acids to increase protein thermostability. Insight from structural bioinformatics combined with computational protein design can successfully guide the selection of stabilizing d-amino acid mutations. Substituting a key glycine in the Trp-Cage mini-protein with d-Gln dramatically stabilizes the fold without altering the protein backbone. Stabilities of individual substitutions can be understood in terms of the balance of intramolecular forces at both the α-helix C-terminus and throughout the protein. PMID:21978298

Amino Acid Interaction with and Adsorption on Clays: FT-IR and Mössbauer Spectroscopy and X-ray Diffractometry Investigations

NASA Astrophysics Data System (ADS)

Benetoli, Luís O. B.; de Souza, Cláudio M. D.; da Silva, Klébson L.; de Souza, Ivan G.; de Santana, Henrique; Paesano, Andrea; da Costa, Antonio C. S.; Zaia, Cássia Thaïs B. V.; Zaia, Dimas A. M.

2007-12-01

In the present paper, the adsorption of amino acids (Ala, Met, Gln, Cys, Asp, Lys, His) on clays (bentonite, kaolinite) was studied at different pH (3.00, 6.00, 8.00). The amino acids were dissolved in seawater, which contains the major elements. There were two main findings in this study. First, amino acids with a charged R group (Asp, Lys, His) and Cys were adsorbed on clays more than Ala, Met and Gln (uncharged R groups). However, 74% of the amino acids in the proteins of modern organisms have uncharged R groups. These results raise some questions about the role of minerals in providing a prebiotic concentration mechanism for amino acids. Several mechanisms are also discussed that could produce peptide with a greater proportion of amino acids with uncharged R groups. Second, Cys could play an important role in prebiotic chemistry besides participating in the structure of peptides/proteins. The FT-IR spectra showed that the adsorption of amino acids on the clays occurs through the amine group. However, the Cys/clay interaction occurs through the sulfhydryl and amine groups. X-ray diffractometry showed that pH affects the bentonite interlayer, and at pH 3.00 the expansion of Cys/bentonite was greater than that of the samples of ethylene glycol/bentonite saturated with Mg. The Mössbauer spectrum for the sample with absorbed Cys showed a large increase (˜20%) in ferrous ions. This means that Cys was able to partially reduce iron present in bentonite. This result is similar to that which occurs with aconitase where the ferric ions are reduced to Fe 2.5.

Raman and surface enhanced Raman spectroscopy of amino acids and peptide

NASA Astrophysics Data System (ADS)

Yuan, Xiaojuan; Gu, Huaimin; Wu, Jiwei; Kang, Jian; Dong, Xiao

2009-08-01

Surface enhanced Raman scattering (SERS) is potentially tool in the characterization of biomolecules such as amino acids, complicated peptides and proteins, and even tissues or living cells. Amino acids and short peptides contain different functional groups. Therefore, they are suitable for the investigations of the competitive-interactions of these functional groups with colloidal silver surfaces. In this paper, Normal Raman and SERS of amino acids Leucine and Isoleucine and short peptide Leu-Leu were measured on the silver colloidal substrate. Raman shifts that stem from different vibrational mode in the molecular inner structure, and the variations of SERS of the samples were analyzed in this study. The results show that different connection of one methyl to the main chains of the isomer amino acids resulted in different vibration modes in the Normal Raman spectra of Leucine and Isoleucine. In the SERS spectra of the isomer amino acids, all frequency shifts are expressed more differently than those in Normal Raman spectra of solid state. Orientation of this isomer amino acids, as well as specific-competitive interactions of their functional groups with the colloidal silver surface, were speculated by detailed spectral analysis of the obtained SERS spectra. In addition, the dipeptide Leu-Leu, as the corresponding homodipeptide of Leucine, was also measured adsorbed on the colloidal silver surface. The SERS spectrum of Leu-Leu is different from its corresponding amino acid Leucine but both of them are adsorbed on the silver surface through the carboxylate moiety.

Hydration of amino acids: FTIR spectra and molecular dynamics studies.

PubMed

Panuszko, Aneta; Adamczak, Beata; Czub, Jacek; Gojło, Emilia; Stangret, Janusz

2015-11-01

The hydration of selected amino acids, alanine, glycine, proline, valine, isoleucine and phenylalanine, has been studied in aqueous solutions by means of FTIR spectra of HDO isotopically diluted in H2O. The difference spectra procedure and the chemometric method have been applied to remove the contribution of bulk water and thus to separate the spectra of solute-affected HDO. To support interpretation of obtained spectral results, molecular dynamics simulations of amino acids were performed. The structural-energetic characteristic of these solute-affected water molecules shows that, on average, water affected by amino acids forms stronger and shorter H-bonds than those in pure water. Differences in the influence of amino acids on water structure have been noticed. The effect of the hydrophobic side chain of an amino acid on the solvent interactions seems to be enhanced because of the specific cooperative coupling of water strong H-bond chain, connecting the carboxyl and amino groups, with the clathrate-like H-bond network surrounding the hydrocarbon side chain. The parameter derived from the spectral data, which corresponds to the contributions of the population of weak hydrogen bonds of water molecules which have been substituted by the stronger ones in the hydration sphere of amino acids, correlated well with the amino acid hydrophobicity indexes.

Interactions of aqueous amino acids and proteins with the (110) surface of ZnS in molecular dynamics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nawrocki, Grzegorz; Cieplak, Marek

2014-03-07

The growing usage of nanoparticles of zinc sulfide as quantum dots and biosensors calls for a theoretical assessment of interactions of ZnS with biomolecules. We employ the molecular-dynamics-based umbrella sampling method to determine potentials of mean force for 20 single amino acids near the ZnS (110) surface in aqueous solutions. We find that five amino acids do not bind at all and the binding energy of the remaining amino acids does not exceed 4.3 kJ/mol. Such energies are comparable to those found for ZnO (and to hydrogen bonds in proteins) but the nature of the specificity is different. Cysteine canmore » bind with ZnS in a covalent way, e.g., by forming the disulfide bond with S in the solid. If this effect is included within a model incorporating the Morse potential, then the potential well becomes much deeper—the binding energy is close to 98 kJ/mol. We then consider tryptophan cage, a protein of 20 residues, and characterize its events of adsorption to ZnS. We demonstrate the relevance of interactions between the amino acids in the selection of optimal adsorbed conformations and recognize the key role of cysteine in generation of lasting adsorption. We show that ZnS is more hydrophobic than ZnO and that the density profile of water is quite different than that forming near ZnO—it has only a minor articulation into layers. Furthermore, the first layer of water is disordered and mobile.« less

Mirrors in the PDB: left-handed alpha-turns guide design with D-amino acids.

PubMed

Annavarapu, Srinivas; Nanda, Vikas

2009-09-22

Incorporating variable amino acid stereochemistry in molecular design has the potential to improve existing protein stability and create new topologies inaccessible to homochiral molecules. The Protein Data Bank has been a reliable, rich source of information on molecular interactions and their role in protein stability and structure. D-amino acids rarely occur naturally, making it difficult to infer general rules for how they would be tolerated in proteins through an analysis of existing protein structures. However, protein elements containing short left-handed turns and helices turn out to contain useful information. Molecular mechanisms used in proteins to stabilize left-handed elements by L-amino acids are structurally enantiomeric to potential synthetic strategies for stabilizing right-handed elements with D-amino acids. Propensities for amino acids to occur in contiguous alpha(L) helices correlate with published thermodynamic scales for incorporation of D-amino acids into alpha(R) helices. Two backbone rules for terminating a left-handed helix are found: an alpha(R) conformation is disfavored at the amino terminus, and a beta(R) conformation is disfavored at the carboxy terminus. Helix capping sidechain-backbone interactions are found which are unique to alpha(L) helices including an elevated propensity for L-Asn, and L-Thr at the amino terminus and L-Gln, L-Thr and L-Ser at the carboxy terminus. By examining left-handed alpha-turns containing L-amino acids, new interaction motifs for incorporating D-amino acids into right-handed alpha-helices are identified. These will provide a basis for de novo design of novel heterochiral protein folds.

Mirrors in the PDB: left-handed α-turns guide design with D-amino acids

PubMed Central

Annavarapu, Srinivas; Nanda, Vikas

2009-01-01

Background Incorporating variable amino acid stereochemistry in molecular design has the potential to improve existing protein stability and create new topologies inaccessible to homochiral molecules. The Protein Data Bank has been a reliable, rich source of information on molecular interactions and their role in protein stability and structure. D-amino acids rarely occur naturally, making it difficult to infer general rules for how they would be tolerated in proteins through an analysis of existing protein structures. However, protein elements containing short left-handed turns and helices turn out to contain useful information. Molecular mechanisms used in proteins to stabilize left-handed elements by L-amino acids are structurally enantiomeric to potential synthetic strategies for stabilizing right-handed elements with D-amino acids. Results Propensities for amino acids to occur in contiguous αL helices correlate with published thermodynamic scales for incorporation of D-amino acids into αR helices. Two backbone rules for terminating a left-handed helix are found: an αR conformation is disfavored at the amino terminus, and a βR conformation is disfavored at the carboxy terminus. Helix capping sidechain-backbone interactions are found which are unique to αL helices including an elevated propensity for L-Asn, and L-Thr at the amino terminus and L-Gln, L-Thr and L-Ser at the carboxy terminus. Conclusion By examining left-handed α-turns containing L-amino acids, new interaction motifs for incorporating D-amino acids into right-handed α-helices are identified. These will provide a basis for de novo design of novel heterochiral protein folds. PMID:19772623

Solubility calculations of branched and linear amino acids using lattice cluster theory

NASA Astrophysics Data System (ADS)

Fischlschweiger, Michael; Enders, Sabine; Zeiner, Tim

2014-09-01

In this work, the activity coefficients and the solubility of amino acids in water were calculated using the lattice cluster theory (LCT) combined with the extended chemical association lattice model allowing self-association as well as cross-association. This permits the study of the influence of the amino acids structure on the thermodynamic properties for the first time. By the used model, the activity coefficient and solubilities of the investigated fourteen amino acids (glycine, alanine, γ-aminobutyric acid, dl-valine, dl-threonine, dl-methionine, l-leucine, l-glutamic acid, l-proline, hydroxyproline, histidine, l-arginine, α-amino valeric acid) could be described in good accordance with experimental data. In the case of different α-amino acids, but different hydrocarbon chains, the same interaction energy parameter can be used within the LCT. All studied amino acids could be modelled using the same parameter for the description of the amino acid association properties. The formed cross-associates contain more amino acids than expressed by the overall mole fraction of the solution. Moreover, the composition of the cross-associates depends on temperature, where the amount of amino acids increases with increasing temperature.

Choline-Based Amino Acid ILs-Collagen Interaction: Enunciating Its Role in Stabilization/Destabilization Phenomena.

PubMed

Tarannum, Aafiya; Rao, J Raghava; Fathima, N Nishad

2018-01-25

Given the potential of productive interaction between choline-based amino acid ionic liquids (CAAILs) and collagen, we investigated the role of four CAAILs, viz., choline serinate, threoninate, lysinate, and phenylalaninate, and the changes mediated by them in the structure of collagen at different hierarchical orderings, that is, at molecular and fibrillar levels. The rheological, dielectric behavior and the secondary structural changes signify the alteration in the triple helical structure of collagen at higher concentrations of CAAILs. A marginal swelling and slight decrease in the thermal stability of rat tail tendon collagen fibers were observed for choline serinate and threoninate, albeit distortions in banding patterns were noticed for choline lysinate and phenylalaninate, suggesting chaotropicity of the ions at the fibrillar level. This signifies the changes in the hydrogen-bonding environment of collagen with increasing concentrations of CAAILs, which could be due to competitive hydrogen bonding between the carbonyl group of amino acid ionic liquids and the hydroxyl groups of collagen.

Amino acid "little Big Bang": representing amino acid substitution matrices as dot products of Euclidian vectors.

PubMed

Zimmermann, Karel; Gibrat, Jean-François

2010-01-04

Sequence comparisons make use of a one-letter representation for amino acids, the necessary quantitative information being supplied by the substitution matrices. This paper deals with the problem of finding a representation that provides a comprehensive description of amino acid intrinsic properties consistent with the substitution matrices. We present a Euclidian vector representation of the amino acids, obtained by the singular value decomposition of the substitution matrices. The substitution matrix entries correspond to the dot product of amino acid vectors. We apply this vector encoding to the study of the relative importance of various amino acid physicochemical properties upon the substitution matrices. We also characterize and compare the PAM and BLOSUM series substitution matrices. This vector encoding introduces a Euclidian metric in the amino acid space, consistent with substitution matrices. Such a numerical description of the amino acid is useful when intrinsic properties of amino acids are necessary, for instance, building sequence profiles or finding consensus sequences, using machine learning algorithms such as Support Vector Machine and Neural Networks algorithms.

Amino Acids and Chirality

NASA Technical Reports Server (NTRS)

Cook, Jamie E.

2012-01-01

Amino acids are among the most heavily studied organic compound class in carbonaceous chondrites. The abundance, distributions, enantiomeric compositions, and stable isotopic ratios of amino acids have been determined in carbonaceous chondrites fi'om a range of classes and petrographic types, with interesting correlations observed between these properties and the class and typc of the chondritcs. In particular, isomeric distributions appear to correlate with parent bodies (chondrite class). In addition, certain chiral amino acids are found in enantiomeric excess in some chondrites. The delivery of these enantiomeric excesses to the early Earth may have contributed to the origin of the homochirality that is central to life on Earth today. This talk will explore the amino acids in carbonaceous chondritcs and their relevance to the origin of life.

Structure-based conformational preferences of amino acids

PubMed Central

Koehl, Patrice; Levitt, Michael

1999-01-01

Proteins can be very tolerant to amino acid substitution, even within their core. Understanding the factors responsible for this behavior is of critical importance for protein engineering and design. Mutations in proteins have been quantified in terms of the changes in stability they induce. For example, guest residues in specific secondary structures have been used as probes of conformational preferences of amino acids, yielding propensity scales. Predicting these amino acid propensities would be a good test of any new potential energy functions used to mimic protein stability. We have recently developed a protein design procedure that optimizes whole sequences for a given target conformation based on the knowledge of the template backbone and on a semiempirical potential energy function. This energy function is purely physical, including steric interactions based on a Lennard-Jones potential, electrostatics based on a Coulomb potential, and hydrophobicity in the form of an environment free energy based on accessible surface area and interatomic contact areas. Sequences designed by this procedure for 10 different proteins were analyzed to extract conformational preferences for amino acids. The resulting structure-based propensity scales show significant agreements with experimental propensity scale values, both for α-helices and β-sheets. These results indicate that amino acid conformational preferences are a natural consequence of the potential energy we use. This confirms the accuracy of our potential and indicates that such preferences should not be added as a design criterion. PMID:10535955

Enantioselective Organocatalytic Aminomethylation of Aldehydes: A Role for Ionic Interactions and Efficient Access to β2-Amino Acids

PubMed Central

Chi, Yonggui; Gellman, Samuel H.

2009-01-01

Organocatalytic Mannich addition of aldehydes to a formaldehyde-derived iminium species catalyzed by proline-derived chiral pyrrolidines provides β-amino aldehydes with ≥ 90% ee. Mechanistic analysis of the proline-catalyzed reactions suggests that non-hydrogen-bonded ionic interactions at the Mannich reaction transition state can influence stereochemical outcome. The β-amino aldehydes from our process bear a substituent adjacent to the carbonyl and can be efficiently converted to protected β2-amino acids, which are important building blocks for β-peptide foldamers that display useful biological activities. PMID:16719457

Characterization of π-stacking interactions between aromatic amino acids and quercetagetin

NASA Astrophysics Data System (ADS)

Akher, Farideh Badichi; Ebrahimi, Ali; Mostafavi, Najmeh

2017-01-01

In the present study, the π-stacking interactions between quercetagetin (QUE), which is one of the most representative flavonol compounds with biological and chemical activities, and some aromatic amino acid (AA) residues has been investigated by the quantum mechanical calculations. The trend in the absolute value of stacking interaction energy |ΔE| with respect to AAs is HIS > PHE > TYR > TPR. The results show that the sum of donor-acceptor interaction energy between AAs and QUE (∑E2) and the sum of electron densities ρ calculated at BCPs and CCPs between the rings (∑ρBCPs and ∑ρCCP) can be useful descriptors for prediction of the ΔE values of the complexes. The Osbnd H bond dissociation enthalpy (BDE) slightly decreases by the π-stacking interaction, which confirms the positive effect of that interaction on the antioxidant activity of QUE. A reverse trend is observed for BDE when is compared with the |ΔE| values. A reliable relationship is also observed between the Muliken spin density (MSD) distributions of the radical species and the most convenient Osbnd H bond dissociations. In addition, reactivity is in good correlation with the antioxidant activity of the complexes.

Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging

NASA Astrophysics Data System (ADS)

Naemat, Abida; Elsheikha, Hany M.; Boitor, Radu A.; Notingher, Ioan

2016-02-01

This study investigates the temporal and spatial interchange of the aromatic amino acid phenylalanine (Phe) between human retinal pigment epithelial cell line (ARPE-19) and tachyzoites of the apicomplexan protozoan parasite Toxoplasma gondii (T. gondii). Stable isotope labelling by amino acids in cell culture (SILAC) is combined with Raman micro-spectroscopy to selectively monitor the incorporation of deuterium-labelled Phe into proteins in individual live tachyzoites. Our results show a very rapid uptake of L-Phe(D8) by the intracellular growing parasite. T. gondii tachyzoites are capable of extracting L-Phe(D8) from host cells as soon as it invades the cell. L-Phe(D8) from the host cell completely replaces the L-Phe within T. gondii tachyzoites 7-9 hours after infection. A quantitative model based on Raman spectra allowed an estimation of the exchange rate of Phe as 0.5-1.6 × 104 molecules/s. On the other hand, extracellular tachyzoites were not able to consume L-Phe(D8) after 24 hours of infection. These findings further our understanding of the amino acid trafficking between host cells and this strictly intracellular parasite. In particular, this study highlights new aspects of the metabolism of amino acid Phe operative during the interaction between T. gondii and its host cell.

Detection of non-protein amino acids in the presence of protein amino acids. II.

NASA Technical Reports Server (NTRS)

Shapshak, P.; Okaji, M.

1972-01-01

Studies conducted with the JEOL 5AH amino acid analyzer are described. This instrument makes possible the programming of the chromatographic process. Data are presented showing the separations of seventeen non-protein amino acids in the presence of eighteen protein amino acids. It is pointed out that distinct separations could be obtained in the case of a number of chemically similar compounds, such as ornithine and lysine, N-amidino alanine and arginine, and iminodiacetic acid and S-carboxymethyl cysteine and aspartic acid.

An In Silico study of TiO2 nanoparticles interaction with twenty standard amino acids in aqueous solution

NASA Astrophysics Data System (ADS)

Liu, Shengtang; Meng, Xuan-Yu; Perez-Aguilar, Jose Manuel; Zhou, Ruhong

2016-11-01

Titanium dioxide (TiO2) is probably one of the most widely used nanomaterials, and its extensive exposure may result in potentially adverse biological effects. Yet, the underlying mechanisms of interaction involving TiO2 NPs and macromolecules, e.g., proteins, are still not well understood. Here, we perform all-atom molecular dynamics simulations to investigate the interactions between TiO2 NPs and the twenty standard amino acids in aqueous solution exploiting a newly developed TiO2 force field. We found that charged amino acids play a dominant role during the process of binding to the TiO2 surface, with both basic and acidic residues overwhelmingly preferred over the non-charged counterparts. By calculating the Potential Mean Force, we showed that Arg is prone to direct binding onto the NP surface, while Lys needs to overcome a ~2 kT free energy barrier. On the other hand, acidic residues tend to form “water bridges” between their sidechains and TiO2 surface, thus displaying an indirect binding. Moreover, the overall preferred positions and configurations of different residues are highly dependent on properties of the first and second solvation water. These molecular insights learned from this work might help with a better understanding of the interactions between biomolecules and nanomaterials.

Combining affinity enrichment, cross-linking with photo-amino acids, and mass spectrometry for probing protein kinase D2 interactions.

PubMed

Häupl, Björn; Ihling, Christian H; Sinz, Andrea

2017-04-07

We present a novel approach that relies on the affinity capture of protein interaction partners from a complex mixture, followed by covalent fixation via UV-induced activation of incorporated diazirine photo-reactive amino acids (photo-methionine and photo-leucine). The captured protein complexes are enzymatically digested and interacting proteins are identified and quantified by label-free LC/MS analysis. Using HeLa cell lysates with photo-methionine and photo-leucine-labeled proteins, we were able to capture and preserve protein interactions that are otherwise elusive in conventional pull-down experiments. Our approach is exemplified for mapping the protein interaction network of protein kinase D2, but has the potential be applied to any protein system. Data are available via ProteomeXchange with identifiers PXD005346 (photo-amino acid incorporation) and PXD005349 (enrichment experiments). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Biometrics from the carbon isotope ratio analysis of amino acids in human hair.

PubMed

Jackson, Glen P; An, Yan; Konstantynova, Kateryna I; Rashaid, Ayat H B

2015-01-01

This study compares and contrasts the ability to classify individuals into different grouping factors through either bulk isotope ratio analysis or amino-acid-specific isotope ratio analysis of human hair. Using LC-IRMS, we measured the isotope ratios of 14 amino acids in hair proteins independently, and leucine/isoleucine as a co-eluting pair, to provide 15 variables for classification. Multivariate analysis confirmed that the essential amino acids and non-essential amino acids were mostly independent variables in the classification rules, thereby enabling the separation of dietary factors of isotope intake from intrinsic or phenotypic factors of isotope fractionation. Multivariate analysis revealed at least two potential sources of non-dietary factors influencing the carbon isotope ratio values of the amino acids in human hair: body mass index (BMI) and age. These results provide evidence that compound-specific isotope ratio analysis has the potential to go beyond region-of-origin or geospatial movements of individuals-obtainable through bulk isotope measurements-to the provision of physical and characteristic traits about the individuals, such as age and BMI. Further development and refinement, for example to genetic, metabolic, disease and hormonal factors could ultimately be of great assistance in forensic and clinical casework. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

Amino Acid and Peptide Immobilization on Oxidized Nanocellulose: Spectroscopic Characterization

PubMed Central

Barazzouk, Saïd; Daneault, Claude

2012-01-01

In this work, oxidized nanocellulose (ONC) was synthesized and chemically coupled with amino acids and peptides using a two step coupling method at room temperature. First, ONC was activated by N-ethyl-N’-(3-dimethylaminopropyl) carbodiimide hydrochloride, forming a stable active ester in the presence of N-hydroxysuccinimide. Second, the active ester was reacted with the amino group of the amino acid or peptide, forming an amide bond between ONC and the grafted molecule. Using this method, the intermolecular interaction of amino acids and peptides was avoided and uniform coupling of these molecules on ONC was achieved. The coupling reaction was very fast in mild conditions and without alteration of the polysaccharide. The coupling products (ONC-amino acids and ONC-peptides) were characterized by transmission electron microscopy and by the absorption, emission, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) spectroscopic techniques. PMID:28348303

Phospholipase D and phosphatidic acid in plant defence response: from protein–protein and lipid–protein interactions to hormone signalling

PubMed Central

Zhao, Jian

2015-01-01

Phospholipase Ds (PLDs) and PLD-derived phosphatidic acids (PAs) play vital roles in plant hormonal and environmental responses and various cellular dynamics. Recent studies have further expanded the functions of PLDs and PAs into plant–microbe interaction. The molecular diversities and redundant functions make PLD–PA an important signalling complex regulating lipid metabolism, cytoskeleton dynamics, vesicle trafficking, and hormonal signalling in plant defence through protein–protein and protein–lipid interactions or hormone signalling. Different PLD–PA signalling complexes and their targets have emerged as fast-growing research topics for understanding their numerous but not yet established roles in modifying pathogen perception, signal transduction, and downstream defence responses. Meanwhile, advanced lipidomics tools have allowed researchers to reveal further the mechanisms of PLD–PA signalling complexes in regulating lipid metabolism and signalling, and their impacts on jasmonic acid/oxylipins, salicylic acid, and other hormone signalling pathways that essentially mediate plant defence responses. This review attempts to summarize the progress made in spatial and temporal PLD/PA signalling as well as PLD/PA-mediated modification of plant defence. It presents an in-depth discussion on the functions and potential mechanisms of PLD–PA complexes in regulating actin filament/microtubule cytoskeleton, vesicle trafficking, and hormonal signalling, and in influencing lipid metabolism-derived metabolites as critical signalling components in plant defence responses. The discussion puts PLD–PA in a broader context in order to guide future research. PMID:25680793

Permeability of membranes to amino acids and modified amino acids: mechanisms involved in translocation

NASA Technical Reports Server (NTRS)

Chakrabarti, A. C.; Deamer, D. W. (Principal Investigator); Miller, S. L. (Principal Investigator)

1994-01-01

The amino acid permeability of membranes is of interest because they are one of the key solutes involved in cell function. Membrane permeability coefficients (P) for amino acid classes, including neutral, polar, hydrophobic, and charged species, have been measured and compared using a variety of techniques. Decreasing lipid chain length increased permeability slightly (5-fold), while variations in pH had only minor effects on the permeability coefficients of the amino acids tested in liposomes. Increasing the membrane surface charge increased the permeability of amino acids of the opposite charge, while increasing the cholesterol content decreased membrane permeability. The permeability coefficients for most amino acids tested were surprisingly similar to those previously measured for monovalent cations such as sodium and potassium (approximately 10(-12)-10(-13) cm s-1). This observation suggests that the permeation rates for the neutral, polar and charged amino acids are controlled by bilayer fluctuations and transient defects, rather than partition coefficients and Born energy barriers. Hydrophobic amino acids were 10(2) more permeable than the hydrophilic forms, reflecting their increased partition coefficient values. External pH had dramatic effects on the permeation rates for the modified amino acid lysine methyl ester in response to transmembrane pH gradients. It was established that lysine methyl ester and other modified short peptides permeate rapidly (P = 10(-2) cm s-1) as neutral (deprotonated) molecules. It was also shown that charge distributions dramatically alter permeation rates for modified di-peptides. These results may relate to the movement of peptides through membranes during protein translocation and to the origin of cellular membrane transport on the early Earth.

A New Paradigm for Creating Amino Acid Chirality

NASA Astrophysics Data System (ADS)

Boyd, Richard N.; Famiano, Michael A.; Kajino, Toshitaka; Onaka, Takashi

2018-06-01

The Supernova Neutrino Amino Acid Processing (SNAAP) model (1) selects left-handed amino acids via the interaction of electron anti-neutrinos with the N nuclei that have been oriented by the strong magnetic field. Within the amino acid molecules, the shielding tensor alters the local magnetic field, and this tensor is sensitive to the molecular chirality. The astrophysical object (2) that might supply the magnetic field and the neutrinos could be a core-collapse supernova, although there are problems with that site. A more likely candidate would be a close binary system consisting of a Wolf-Rayet star with a neutron star companion. The accretion disk that would form around the neutron star could enable dust formation, as well as meteoroids and planets, and the temperatures in the outer portions would accommodate amino acid formation. When the WR star explodes it provides the intense anti-neutrino flux, while the neutron star and the WR star provide the magnetic field. Quantum molecular calculations that included perturbation effects on the shielding tensor for nitrogen from the reorientation of the molecular electric dipole have been performed. They have found the amino acids moving in an external magnetic field to be physically distinct, so the anti-neutrinos from the WR star interacting with the N nuclei can perform a chirality dependent selection. An enantiomeric excess of a few percent has been found for isovaline in an aqueous environment. Alanine was found to have a comparable, but slightly lower, enantiomeric excess. This model suggests that our Solar System might have been created by a system such as this, as has also been suggested by recent measurements of unstable nuclides in our local environment.M.A. Famiano et al., Astrobiology 18, 190 (2018)R.N. Boyd et al., Astrophys. J. (in press), arXiv.org/abs/a802.08285

A Comparative Proteomic Analysis of the Simple Amino Acid Repeat Distributions in Plasmodia Reveals Lineage Specific Amino Acid Selection

PubMed Central

Dalby, Andrew R.

2009-01-01

Background Microsatellites have been used extensively in the field of comparative genomics. By studying microsatellites in coding regions we have a simple model of how genotypic changes undergo selection as they are directly expressed in the phenotype as altered proteins. The simplest of these tandem repeats in coding regions are the tri-nucleotide repeats which produce a repeat of a single amino acid when translated into proteins. Tri-nucleotide repeats are often disease associated, and are also known to be unstable to both expansion and contraction. This makes them sensitive markers for studying proteome evolution, in closely related species. Results The evolutionary history of the family of malarial causing parasites Plasmodia is complex because of the life-cycle of the organism, where it interacts with a number of different hosts and goes through a series of tissue specific stages. This study shows that the divergence between the primate and rodent malarial parasites has resulted in a lineage specific change in the simple amino acid repeat distribution that is correlated to A–T content. The paper also shows that this altered use of amino acids in SAARs is consistent with the repeat distributions being under selective pressure. Conclusions The study shows that simple amino acid repeat distributions can be used to group related species and to examine their phylogenetic relationships. This study also shows that an outgroup species with a similar A–T content can be distinguished based only on the amino acid usage in repeats, and suggest that this might be a useful feature for proteome clustering. The lineage specific use of amino acids in repeat regions suggests that comparative studies of SAAR distributions between proteomes gives an insight into the mechanisms of expansion and the selective pressures acting on the organism. PMID:19597555

Pairwise amino acid secondary structural propensities

NASA Astrophysics Data System (ADS)

Chemmama, Ilan E.; Chapagain, Prem P.; Gerstman, Bernard S.

2015-04-01

We investigate the propensities for amino acids to form a specific secondary structure when they are paired with other amino acids. Our investigations use molecular dynamics (MD) computer simulations, and we compare the results to those from the Protein Data Bank (PDB). Proper comparison requires weighting of the MD results in a manner consistent with the relative frequency of appearance in the PDB of each possible pair of amino acids. We find that the propensity for an amino acid to assume a secondary structure varies dramatically depending on the amino acid that is before or after it in the primary sequence. This cooperative effect means that when selecting amino acids to facilitate the formation of a secondary structure in peptide engineering experiments, the adjacent amino acids must be considered. We also examine the preference for a secondary structure in bacterial proteins and compare the results to those of human proteins.

AFAL: a web service for profiling amino acids surrounding ligands in proteins

NASA Astrophysics Data System (ADS)

Arenas-Salinas, Mauricio; Ortega-Salazar, Samuel; Gonzales-Nilo, Fernando; Pohl, Ehmke; Holmes, David S.; Quatrini, Raquel

2014-11-01

With advancements in crystallographic technology and the increasing wealth of information populating structural databases, there is an increasing need for prediction tools based on spatial information that will support the characterization of proteins and protein-ligand interactions. Herein, a new web service is presented termed amino acid frequency around ligand (AFAL) for determining amino acids type and frequencies surrounding ligands within proteins deposited in the Protein Data Bank and for assessing the atoms and atom-ligand distances involved in each interaction (availability: http://structuralbio.utalca.cl/AFAL/index.html). AFAL allows the user to define a wide variety of filtering criteria (protein family, source organism, resolution, sequence redundancy and distance) in order to uncover trends and evolutionary differences in amino acid preferences that define interactions with particular ligands. Results obtained from AFAL provide valuable statistical information about amino acids that may be responsible for establishing particular ligand-protein interactions. The analysis will enable investigators to compare ligand-binding sites of different proteins and to uncover general as well as specific interaction patterns from existing data. Such patterns can be used subsequently to predict ligand binding in proteins that currently have no structural information and to refine the interpretation of existing protein models. The application of AFAL is illustrated by the analysis of proteins interacting with adenosine-5'-triphosphate.

AFAL: a web service for profiling amino acids surrounding ligands in proteins.

PubMed

Arenas-Salinas, Mauricio; Ortega-Salazar, Samuel; Gonzales-Nilo, Fernando; Pohl, Ehmke; Holmes, David S; Quatrini, Raquel

2014-11-01

With advancements in crystallographic technology and the increasing wealth of information populating structural databases, there is an increasing need for prediction tools based on spatial information that will support the characterization of proteins and protein-ligand interactions. Herein, a new web service is presented termed amino acid frequency around ligand (AFAL) for determining amino acids type and frequencies surrounding ligands within proteins deposited in the Protein Data Bank and for assessing the atoms and atom-ligand distances involved in each interaction (availability: http://structuralbio.utalca.cl/AFAL/index.html ). AFAL allows the user to define a wide variety of filtering criteria (protein family, source organism, resolution, sequence redundancy and distance) in order to uncover trends and evolutionary differences in amino acid preferences that define interactions with particular ligands. Results obtained from AFAL provide valuable statistical information about amino acids that may be responsible for establishing particular ligand-protein interactions. The analysis will enable investigators to compare ligand-binding sites of different proteins and to uncover general as well as specific interaction patterns from existing data. Such patterns can be used subsequently to predict ligand binding in proteins that currently have no structural information and to refine the interpretation of existing protein models. The application of AFAL is illustrated by the analysis of proteins interacting with adenosine-5'-triphosphate.

PCI-GC-MS-MS approach for identification of non-amino organic acid and amino acid profiles.

PubMed

Luan, Hemi; Yang, Lin; Ji, Fenfen; Cai, Zongwei

2017-03-15

Alkyl chloroformate have been wildly used for the fast derivatization of metabolites with amino and/or carboxyl groups, coupling of powerful separation and detection systems, such as GC-MS, which allows the comprehensive analysis of non-amino organic acids and amino acids. The reagents involving n-alkyl chloroformate and n-alcohol are generally employed for providing symmetric labeling terminal alkyl chain with the same length. Here, we developed an asymmetric labeling strategy and positive chemical ionization gas chromatography-tandem mass spectrometry (PCI-GC-MS-MS) approach for determination of non-amino organic acids and amino acids, as well as the short chain fatty acids. Carboxylic and amino groups could be selectively labelled by propyl and ethyl groups, respectively. The specific neutral loss of C 3 H 8 O (60Da), C 3 H 5 O 2 (74Da) and C 4 H 8 O 2 (88Da) were useful in the selective identification for qualitative analysis of organic acids and amino acid derivatives. PCI-GC-MS-MS using multiple reaction monitoring (MRM) was applied for semi-quantification of typical non-amino organic acids and amino acids. This method exhibited a wide range of linear range, good regression coefficient (R 2 ) and repeatability. The relative standard deviation (RSD) of targeted metabolites showed excellent intra- and inter-day precision (<5%). Our method provided a qualitative and semi-quantitative PCI-GC-MS-MS, coupled with alkyl chloroformate derivatization. Copyright © 2016 Elsevier B.V. All rights reserved.

DNA–protein π-interactions in nature: abundance, structure, composition and strength of contacts between aromatic amino acids and DNA nucleobases or deoxyribose sugar

PubMed Central

Wilson, Katie A.; Kellie, Jennifer L.; Wetmore, Stacey D.

2014-01-01

Four hundred twenty-eight high-resolution DNA–protein complexes were chosen for a bioinformatics study. Although 164 crystal structures (38% of those searched) contained no interactions, 574 discrete π–contacts between the aromatic amino acids and the DNA nucleobases or deoxyribose were identified using strict criteria, including visual inspection. The abundance and structure of the interactions were determined by unequivocally classifying the contacts as either π–π stacking, π–π T-shaped or sugar–π contacts. Three hundred forty-four nucleobase–amino acid π–π contacts (60% of all interactions identified) were identified in 175 of the crystal structures searched. Unprecedented in the literature, 230 DNA–protein sugar–π contacts (40% of all interactions identified) were identified in 137 crystal structures, which involve C–H···π and/or lone–pair···π interactions, contain any amino acid and can be classified according to sugar atoms involved. Both π–π and sugar–π interactions display a range of relative monomer orientations and therefore interaction energies (up to –50 (–70) kJ mol−1 for neutral (charged) interactions as determined using quantum chemical calculations). In general, DNA–protein π-interactions are more prevalent than perhaps currently accepted and the role of such interactions in many biological processes may yet to be uncovered. PMID:24744240

Dietary Deficiency of Essential Amino Acids Rapidly Induces Cessation of the Rat Estrous Cycle

PubMed Central

Bannai, Makoto; Ichimaru, Toru; Nakano, Sayako; Murata, Takuya; Higuchi, Takashi; Takahashi, Michio

2011-01-01

Reproductive functions are regulated by the sophisticated coordination between the neuronal and endocrine systems and are sustained by a proper nutritional environment. Female reproductive function is vulnerable to effects from dietary restrictions, suggesting a transient adaptation that prioritizes individual survival over reproduction until a possible future opportunity for satiation. This adaptation could also partially explain the existence of amenorrhea in women with anorexia nervosa. Because amino acid nutritional conditions other than caloric restriction uniquely alters amino acid metabolism and affect the hormonal levels of organisms, we hypothesized that the supply of essential amino acids in the diet plays a pivotal role in the maintenance of the female reproductive system. To test this hypothesis, we examined ovulatory cyclicity in female rats under diets that were deficient in threonine, lysine, tryptophan, methionine or valine. Ovulatory cyclicity was monitored by daily cytological evaluations of vaginal smears. After continuous feeding of the deficient diet, a persistent diestrus or anovulatory state was induced most quickly by the valine-deficient diet and most slowly by the lysine-deficient diet. A decline in the systemic insulin-like growth factor 1 level was associated with a dietary amino acid deficiency. Furthermore, a paired group of rats that were fed an isocaloric diet with balanced amino acids maintained normal estrous cyclicity. These disturbances of the estrous cycle by amino acid deficiency were quickly reversed by the consumption of a normal diet. The continuous anovulatory state in this study is not attributable to a decrease in caloric intake but to an imbalance in the dietary amino acid composition. With a shortage of well-balanced amino acid sources, reproduction becomes risky for both the mother and the fetus. It could be viewed as an adaptation to the diet, diverting resources away from reproduction and reallocating them to

Potential use of carbon-11 labeled alpha-aminoisobutyric acid (AIB) as an in vivo tracer of amino acid uptake in differing metabolic states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conti, P.S.; Starnes, H.F.; Brennan, M.F.

1986-05-01

AIB has been used as a model amino acid for the evaluation of alanine-preferring amino acid transport. Hormonal factors and starvation alter the tissue distribution of amino acids, particularly in liver and muscle. With positron emission tomography and labeling of biochemical tracers with C-11, (t1/2=20.4 min), it is now possible to study amino acid kinetics in vivo using external imaging. In order to investigate the utility of C-11 AIB as an in vivo tracer of altered tissue metabolism, C-14 AIB was studied in groups of rats with either streptozotocin-induced diabetes, insulin-induced hypoglycemia or starvation. The data suggest an increased aminomore » acid uptake in liver in starvation, an increased uptake in muscle in response to insulin and associated hypoglycemia and decreased transport in muscle in starvation, as seen by other investigators. These results suggest that C-11 AIB may be useful as an in vivo monitor of metabolic changes in body tissues.« less

D-Amino Acids in Living Higher Organisms

NASA Astrophysics Data System (ADS)

Fujii, Noriko

2002-04-01

The homochirality of biological amino acids (L-amino acids) and of the RNA/DNA backbone (D-ribose) might have become established before the origin of life. It has been considered that D-amino acids and L-sugars were eliminated on the primitive Earth. Therefore, the presence and function of D-amino acids in living organisms have not been studied except for D-amino acids in the cell walls of microorganisms. However, D-amino acids were recently found in various living higher organisms in the form of free amino acids, peptides, and proteins. Free D-aspartate and D-serine are present and may have important physiological functions in mammals. D-amino acids in peptides are well known as opioid peptides and neuropeptides. In protein, D-aspartate residues increase during aging. This review deals with recent advances in the study of D-amino acids in higher organisms.

Branched-chain amino acids and brain function.

PubMed

Fernstrom, John D

2005-06-01

Branched-chain amino acids (BCAAs) influence brain function by modifying large, neutral amino acid (LNAA) transport at the blood-brain barrier. Transport is shared by several LNAAs, notably the BCAAs and the aromatic amino acids (ArAAs), and is competitive. Consequently, when plasma BCAA concentrations rise, which can occur in response to food ingestion or BCAA administration, or with the onset of certain metabolic diseases (e.g., uncontrolled diabetes), brain BCAA concentrations rise, and ArAA concentrations decline. Such effects occur acutely and chronically. Such reductions in brain ArAA concentrations have functional consequences: biochemically, they reduce the synthesis and the release of neurotransmitters derived from ArAAs, notably serotonin (from tryptophan) and catecholamines (from tyrosine and phenylalanine). The functional effects of such neurochemical changes include altered hormonal function, blood pressure, and affective state. Although the BCAAs thus have biochemical and functional effects in the brain, few attempts have been made to characterize time-course or dose-response relations for such effects. And, no studies have attempted to identify levels of BCAA intake that might produce adverse effects on the brain. The only "model" of very high BCAA exposure is a very rare genetic disorder, maple syrup urine disease, a feature of which is substantial brain dysfunction but that probably cannot serve as a useful model for excessive BCAA intake by normal individuals. Given the known biochemical and functional effects of the BCAAs, it should be a straightforward exercise to design studies to assess dose-response relations for biochemical and functional effects and, in this context, to explore for adverse effect thresholds.

Solubility of xenon in amino-acid solutions. II. Nine less-soluble amino acids

NASA Astrophysics Data System (ADS)

Kennan, Richard P.; Himm, Jeffrey F.; Pollack, Gerald L.

1988-05-01

Ostwald solubility (L) of xenon gas, as the radioisotope 133Xe, has been measured as a function of solute concentration, at 25.0 °C, in aqueous solutions of nine amino acids. The amino-acid concentrations investigated covered much of their solubility ranges in water, viz., asparagine monohydrate (0-0.19 M), cysteine (0-1.16 M), glutamine (0-0.22 M), histidine (0-0.26 M), isoleucine (0-0.19 M), methionine (0-0.22 M), serine (0-0.38 M), threonine (0-1.4 M), and valine (0-0.34 M). We have previously reported solubility results for aqueous solutions of six other, generally more soluble, amino acids (alanine, arginine, glycine, hydroxyproline, lysine, and proline), of sucrose and sodium chloride. In general, L decreases approximately linearly with increasing solute concentration in these solutions. If we postulate that the observed decreases in gas solubility are due to hydration, the results under some assumptions can be used to calculate hydration numbers (H), i.e., the number of H2O molecules associated with each amino-acid solute molecule. The average values of hydration number (H¯) obtained at 25.0 °C are 15.3±1.5 for asparagine, 6.8±0.3 for cysteine, 11.5±1.1 for glutamine, 7.3±0.7 for histidine, 5.9±0.4 for isoleucine, 10.6±0.8 for methionine, 11.2±1.3 for serine, 7.7± 1.0 for threonine, and 6.6±0.6 for valine. We have also measured the temperature dependence of solubility L(T) from 5-40 °C for arginine, glycine, and proline, and obtained hydration numbers H¯(T) in this range. Between 25-40 °C, arginine has an H¯ near zero. This may be evidence for an attractive interaction between xenon and arginine molecules in aqueous solution.

Catalytic and inhibiting effect of amino acids on the porphyrin metallation reactions

NASA Astrophysics Data System (ADS)

Mamardashvili, Galina M.; Zhdanova, Daria Yu.; Mamardashvili, Nugzar Zh.; Koifman, Oskar I.; Dehaen, Wim

In the present work, using the interaction of tetra-(4-sulfophenyl)porphyrin with copper(II) chloride as an example, it has been shown how different amino acid additives (glycine, valine, leucine and tryptophan) catalyze or inhibit the formation of Cu-porphyrin as a function of the chemical environment (borate buffer (pH7.4), DMSO) and the concentration of the additive. It has been demonstrated that the type of amino acid affects the complexation reaction rate. Possible mechanisms of metalloporphyrin formation and the ways of their acceleration are discussed. Ways in which different amino acid additives catalyze or inhibit the interaction of tetra-(4-sulfophenyl)porphyrin with copper(II) chloride are examined.

Amino acid analogs for tumor imaging

DOEpatents

Goodman, M.M.; Shoup, T.

1998-09-15

The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

Amino acid analogs for tumor imaging

DOEpatents

Goodman, M.M.; Shoup, T.

1998-10-06

The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

Amino acid analogs for tumor imaging

DOEpatents

Goodman, Mark M.; Shoup, Timothy

1998-09-15

The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

Amino acid analogs for tumor imaging

DOEpatents

Goodman, Mark M.; Shoup, Timothy

1998-10-06

The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

Enantiomeric excesses in meteoritic amino acids

NASA Technical Reports Server (NTRS)

Cronin, J. R.; Pizzarello, S.

1997-01-01

Gas chromatographic-mass spectral analyses of the four stereoisomers of 2-amino-2,3-dimethylpentanoic acid (dl-alpha-methylisoleucine and dl-alpha-methylalloisoleucine) obtained from the Murchison meteorite show that the L enantiomer occurs in excess (7.0 and 9.1%, respectively) in both of the enantiomeric pairs. Similar results were obtained for two other alpha-methyl amino acids, isovaline and alpha-methylnorvaline, although the alpha hydrogen analogs of these amino acids, alpha-amino-n-butyric acid and norvaline, were found to be racemates. With the exception of alpha-amino-n-butyric acid, these amino acids are either unknown or of limited occurrence in the biosphere. Because carbonaceous chondrites formed 4.5 billion years ago, the results are indicative of an asymmetric influence on organic chemical evolution before the origin of life.

Phospholipase D and phosphatidic acid in plant defence response: from protein-protein and lipid-protein interactions to hormone signalling.

PubMed

Zhao, Jian

2015-04-01

Phospholipase Ds (PLDs) and PLD-derived phosphatidic acids (PAs) play vital roles in plant hormonal and environmental responses and various cellular dynamics. Recent studies have further expanded the functions of PLDs and PAs into plant-microbe interaction. The molecular diversities and redundant functions make PLD-PA an important signalling complex regulating lipid metabolism, cytoskeleton dynamics, vesicle trafficking, and hormonal signalling in plant defence through protein-protein and protein-lipid interactions or hormone signalling. Different PLD-PA signalling complexes and their targets have emerged as fast-growing research topics for understanding their numerous but not yet established roles in modifying pathogen perception, signal transduction, and downstream defence responses. Meanwhile, advanced lipidomics tools have allowed researchers to reveal further the mechanisms of PLD-PA signalling complexes in regulating lipid metabolism and signalling, and their impacts on jasmonic acid/oxylipins, salicylic acid, and other hormone signalling pathways that essentially mediate plant defence responses. This review attempts to summarize the progress made in spatial and temporal PLD/PA signalling as well as PLD/PA-mediated modification of plant defence. It presents an in-depth discussion on the functions and potential mechanisms of PLD-PA complexes in regulating actin filament/microtubule cytoskeleton, vesicle trafficking, and hormonal signalling, and in influencing lipid metabolism-derived metabolites as critical signalling components in plant defence responses. The discussion puts PLD-PA in a broader context in order to guide future research. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Probing Protein Structure by Amino Acid-Specific Covalent Labeling and Mass Spectrometry

PubMed Central

Mendoza, Vanessa Leah; Vachet, Richard W.

2009-01-01

For many years, amino acid-specific covalent labeling has been a valuable tool to study protein structure and protein interactions, especially for systems that are difficult to study by other means. These covalent labeling methods typically map protein structure and interactions by measuring the differential reactivity of amino acid side chains. The reactivity of amino acids in proteins generally depends on the accessibility of the side chain to the reagent, the inherent reactivity of the label and the reactivity of the amino acid side chain. Peptide mass mapping with ESI- or MALDI-MS and peptide sequencing with tandem MS are typically employed to identify modification sites to provide site-specific structural information. In this review, we describe the reagents that are most commonly used in these residue-specific modification reactions, details about the proper use of these covalent labeling reagents, and information about the specific biochemical problems that have been addressed with covalent labeling strategies. PMID:19016300

Significance of Nanoparticles and the Role of Amino Acids in Structuring Them-A Review.

PubMed

Kulandaisamy, Arockia Jayalatha; Rayappan, John Bosco Balaguru

2018-08-01

Nanoparticles has occupied an eminent place in our tech-facilitated society. The processes involved in synthesizing nanoparticles are important not only to find their applications, but also to make them eco-friendly. Attempts are being made to replace the use of harmful surfactants/reagents by amino acids, in the due course of nanoparticle synthesis. Especially in synthesizing the multifunctional metal and metal oxide nanoparticles the use of amino acids as surfactant/as catalyst, helps to obtain required size and shape. Amino acids have the inherent property in directing and assembling the superstructures. They have the tendency to act as a capping agent and their presence during the synthesis processes alters the synthesized particles' morphology. Review has been made to study the role of amino acids like histidine, lysine, arginine in structuring ZnO, FeO, Au and Ag nanoparticles. The change in their morphology that resulted due to the addition of amino acids has been compared. It is important to understand the role of amino acids in synthesizing the nanoparticles, and so it is more important to understand the internal energy variation of the same. To achieve this, the interaction between the bio (amino acids) and non-bio (metal and metal oxide) nanoparticles are to be discussed both experimentally and theoretically. At times the theoretical characterization, especially at low dimensions, help us to understand inter-particle interaction and intra-particle interaction by determining their chemical potential and Lennard-Jones potential. This review has been concluded with a model to characterize the precursor solution (amino acids and inorganic materials) by considering the Equation of State for liquids, which could also be extended to determine the structure factor of nanoparticles.

A dominant conformational role for amino acid diversity in minimalist protein–protein interfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilbreth, Ryan N.; Esaki, Kaori; Koide, Akiko

Recent studies have shown that highly simplified interaction surfaces consisting of combinations of just two amino acids, Tyr and Ser, exhibit high affinity and specificity. The high functional levels of such minimalist interfaces might thus indicate small contributions of greater amino acid diversity seen in natural interfaces. Toward addressing this issue, we have produced a pair of binding proteins built on the fibronectin type III scaffold, termed “monobodies.” One monobody contains the Tyr/Ser binary-code interface (termed YS) and the other contains an expanded amino acid diversity interface (YSX), but both bind to an identical target, maltose-binding protein. The YSX monobodymore » bound with higher affinity, a slower off rate and a more favorable enthalpic contribution than the YS monobody. High-resolution X-ray crystal structures revealed that both proteins bound to an essentially identical epitope, providing a unique opportunity to directly investigate the role of amino acid diversity in a protein interaction interface. Surprisingly, Tyr still dominates the YSX paratope and the additional amino acid types are primarily used to conformationally optimize contacts made by tyrosines. Scanning mutagenesis showed that while all contacting Tyr side chains are essential in the YS monobody, the YSX interface was more tolerant to mutations. These results suggest that the conformational, not chemical, diversity of additional types of amino acids provided higher functionality and evolutionary robustness, supporting the dominant role of Tyr and the importance of conformational diversity in forming protein interaction interfaces.« less

A Dominant Conformational Role for Amino Acid Diversity in Minimalist Protein-Protein Interfaces

PubMed Central

Gilbreth, Ryan N.; Esaki, Kaori; Koide, Akiko; Sidhu, Sachdev S.; Koide, Shohei

2008-01-01

Recent studies have shown that highly simplified interaction surfaces consisting of combinations of just two amino acids, Tyr and Ser, exhibit high affinity and specificity. The high functional levels of such minimalist interfaces might thus indicate small contributions of greater amino acid diversity seen in natural interfaces. Toward addressing this issue, we have produced a pair of binding proteins built on the fibronectin type III scaffold, termed “monobodies”. One monobody contains the Tyr/Ser binary-code interface (termed YS) and the other contains an expanded amino acid diversity interface (YSX), but both bind to an identical target, maltose binding protein (MBP). The YSX monobody bound with higher affinity, a slower off rate and a more favorable enthalpic contribution than the YS monobody. High-resolution x-ray crystal structures revealed that both proteins bound to an essentially identical epitope, providing a unique opportunity to directly investigate the role of amino acid diversity in a protein interaction interface. Surprisingly, Tyr still dominates the YSX paratope and the additional amino acid types are primarily used to conformationally optimize contacts made by tyrosines. Scanning mutagenesis showed that while all contacting Tyr side-chains are essential in the YS monobody, the YSX interface was more tolerant to mutations. These results suggest that the conformational, not chemical, diversity of additional types of amino acids provided higher functionality and evolutionary robustness, supporting the dominant role of Tyr and the importance of conformational diversity in forming protein interaction interfaces. PMID:18602117

Physiological role of D-amino acid-N-acetyltransferase of Saccharomyces cerevisiae: detoxification of D-amino acids.

PubMed

Yow, Geok-Yong; Uo, Takuma; Yoshimura, Tohru; Esaki, Nobuyoshi

2006-03-01

Saccharomyces cerevisiae is sensitive to D-amino acids: those corresponding to almost all proteinous L-amino acids inhibit the growth of yeast even at low concentrations (e.g. 0.1 mM). We have determined that D-amino acid-N-acetyltransferase (DNT) of the yeast is involved in the detoxification of D-amino acids on the basis of the following findings. When the DNT gene was disrupted, the resulting mutant was far less tolerant to D-amino acids than the wild type. However, when the gene was overexpressed with a vector plasmid p426Gal1 in the wild type or the mutant S. cerevisiae as a host, the recombinant yeast, which was found to show more than 100 times higher DNT activity than the wild type, was much more tolerant to D-amino acids than the wild type. We further confirmed that, upon cultivation with D-phenylalanine, N-acetyl-D-phenylalanine was accumulated in the culture but not in the wild type and hpa3Delta cells overproducing DNT cells. Thus, D-amino acids are toxic to S. cerevisiae but are detoxified with DNT by N-acetylation preceding removal from yeast cells.

Adrenal hormones and the anorectic response and adaptation of rats to amino acid imbalance.

PubMed

Hammer, V A; Gietzen, D W; Sworts, V D; Beverly, J L; Rogers, Q R

1990-12-01

The role of adrenal function in the anorectic response and adaptation of rats to a diet with an isoleucine (Ile) imbalance was investigated. In the first of four experiments, rats were fed a mildly Ile-imbalanced diet after treatment with metyrapone, and inhibitor of glucocorticoid synthesis. In two separate experiments, rats were presented with either a mildly or severely Ile-imbalanced diet (4.93 and 9.86% imbalanced amino acid mixture, respectively) after bilateral adrenalectomy. Finally, the effects of ICS 205-930, a serotonin-3 receptor antagonist, on the intake of mildly Ile-imbalanced diet were tested in adrenalectomized animals. In each experiment a 2 X 2 factorial design was used. Neither metyrapone nor adrenalectomy altered the initial depression in the intake of an imbalanced diet. The adaptation phase in the response of adrenalectomized rats fed a mildly Ile-imbalanced diet was not different from that of controls, but adrenalectomized rats fed severely Ile-imbalanced diets were unable to adapt. Adrenalectomy did not alter the anti-anoretic activity of ICS 205-930 in this model. These results suggest that adrenal hormones are not necessary for the initial anoretic response or adaptation of rats to an Ile-imbalanced diet, nor are they implicated in the anti-anorectic effect of serotonin-3 blockade.

Dissolved Divalent Metal and pH Effects on Amino Acid Polymerization: A Thermodynamic Evaluation.

PubMed

Kitadai, Norio

2017-03-01

Polymerization of amino acids is a fundamentally important step for the chemical evolution of life. Nevertheless, its response to changing environmental conditions has not yet been well understood because of the lack of reliable quantitative information. For thermodynamics, detailed prediction over diverse combinations of temperature and pH has been made only for a few amino acid-peptide systems. This study used recently reported thermodynamic dataset for the polymerization of the simplest amino acid "glycine (Gly)" to its short peptides (di-glycine and tri-glycine) to examine chemical and structural characteristics of amino acids and peptides that control the temperature and pH dependence of polymerization. Results showed that the dependency is strongly controlled by the intramolecular distance between the amino and carboxyl groups in an amino acid structure, although the side-chain group role is minor. The polymerization behavior of Gly reported earlier in the literature is therefore expected to be a typical feature for those of α-amino acids. Equilibrium calculations were conducted to examine effects of dissolved metals as a function of pH on the monomer-polymer equilibria of Gly. Results showed that metals shift the equilibria toward the monomer side, particularly at neutral and alkaline pH. Metals that form weak interaction with Gly (e.g., Mg 2+ ) have no noticeable influence on the polymerization, although strong interaction engenders significant decrease of the equilibrium concentrations of Gly peptides. Considering chemical and structural characteristics of Gly and Gly peptides that control their interactions with metals, it can be expected that similar responses to the addition of metals are applicable in the polymerization of neutral α-amino acids. Neutral and alkaline aqueous environments with dissolved metals having high affinity with neutral α-amino acids (e.g., Cu 2+ ) are therefore not beneficial places for peptide bond formation on the primitive

Amino Acid Side Chain Interactions in the Presence of Salts

PubMed Central

Hassan, Sergio A.

2005-01-01

The effects of salt on the intermolecular interactions between polar/charged amino acids are investigated through molecular dynamics simulations. The mean forces and associated potentials are calculated for NaCl salt in the 0–2 M concentration range at 298 K. It is found that the addition of salt may stabilize or destabilize the interactions, depending on the nature of the interacting molecules. The degree of (de)stabilization is quantified, and the origin of the salt-dependent modulation is discussed based upon an analysis of solvent density profiles. To gain insight into the molecular origin of the salt modulation, spatial distribution functions (sdf’s) are calculated, revealing a high degree of solvent structuredness in all cases. The peaks in the sdf’s are consistent with long-range hydrogen-bonding networks connecting the solute hydrophilic groups, and that contribute to their intermolecular solvent-induced forces. The restructuring of water around the solutes as they dissociate from close contact is analyzed. This analysis offers clues on how the solvent structure modulates the effective intermolecular interactions in complex solutes. This modulation results from a critical balance between bulk electrostatic forces and those exerted by (i) the water molecules in the structured region between the monomers, which is disrupted by ions that transiently enter the hydration shells, and (ii) the ions in the hydration shells in direct interactions with the solutes. The implications of these findings in protein/ligand (noncovalent) association/dissociation mechanisms are briefly discussed. PMID:16479276

Entropy and enthalpy of interaction between amino acid side chains in nanopores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaitheeswaran, S., E-mail: vaithee05@gmail.com; Thirumalai, D.; Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742

2014-12-14

Understanding the stabilities of proteins in nanopores requires a quantitative description of confinement induced interactions between amino acid side chains. We use molecular dynamics simulations to study the nature of interactions between the side chain pairs ALA-PHE, SER-ASN, and LYS-GLU in bulk water and in water-filled nanopores. The temperature dependence of the bulk solvent potentials of mean force and the interaction free energies in cylindrical and spherical nanopores is used to identify the corresponding entropic and enthalpic components. The entropically stabilized hydrophobic interaction between ALA and PHE in bulk water is enthalpically dominated upon confinement depending on the relative orientationsmore » between the side chains. In the case of SER-ASN, hydrogen bonded configurations that are similar in bulk water are thermodynamically distinct in a cylindrical pore, thus making rotamer distributions different from those in the bulk. Remarkably, salt bridge formation between LYS-GLU is stabilized by entropy in contrast to the bulk. Implications of our findings for confinement-induced alterations in protein stability are briefly outlined.« less

An amino acid depleted cell-free protein synthesis system for the incorporation of non-canonical amino acid analogs into proteins.

PubMed

Singh-Blom, Amrita; Hughes, Randall A; Ellington, Andrew D

2014-05-20

Residue-specific incorporation of non-canonical amino acids into proteins is usually performed in vivo using amino acid auxotrophic strains and replacing the natural amino acid with an unnatural amino acid analog. Herein, we present an efficient amino acid depleted cell-free protein synthesis system that can be used to study residue-specific replacement of a natural amino acid by an unnatural amino acid analog. This system combines a simple methodology and high protein expression titers with a high-efficiency analog substitution into a target protein. To demonstrate the productivity and efficacy of a cell-free synthesis system for residue-specific incorporation of unnatural amino acids in vitro, we use this system to show that 5-fluorotryptophan and 6-fluorotryptophan substituted streptavidin retain the ability to bind biotin despite protein-wide replacement of a natural amino acid for the amino acid analog. We envisage this amino acid depleted cell-free synthesis system being an economical and convenient format for the high-throughput screening of a myriad of amino acid analogs with a variety of protein targets for the study and functional characterization of proteins substituted with unnatural amino acids when compared to the currently employed in vivo methodologies. Copyright © 2014 Elsevier B.V. All rights reserved.

The interaction of amino acids with macrocyclic pH probes of pseudopeptidic nature.

PubMed

Izquierdo, M Angeles; Wadhavane, Prashant D; Vigara, Laura; Burguete, M Isabel; Galindo, Francisco; Luis, Santiago V

2017-08-09

The fluorescence quenching, by a series of amino acids, of pseudopeptidic compounds acting as probes for cellular acidity has been investigated. It has been found that amino acids containing electron-rich aromatic side chains like Trp or Tyr, as well as Met quench the emission of the probes mainly via a collisional mechanism, with Stern-Volmer constants in the 7-43 M -1 range, while other amino acids such as His, Val or Phe did not cause deactivation of the fluorescence. Only a minor contribution of a static quenching due to the formation of ground-state complexes has been found for Trp and Tyr, with association constants in the 9-24 M -1 range. For these ground-state complexes, a comparison between the macrocyclic probes and an open chain analogue reveals the existence of a moderate macrocyclic effect due to the preorganization of the probes in the more rigid structure.

Noncoded amino acids in protein engineering: Structure-activity relationship studies of hirudin-thrombin interaction.

PubMed

De Filippis, Vincenzo; Acquasaliente, Laura; Pontarollo, Giulia; Peterle, Daniele

2018-01-01

The advent of recombinant DNA technology allowed to site-specifically insert, delete, or mutate almost any amino acid in a given protein, significantly improving our knowledge of protein structure, stability, and function. Nevertheless, a quantitative description of the physical and chemical basis that makes a polypeptide chain to efficiently fold into a stable and functionally active conformation is still elusive. This mainly originates from the fact that nature combined, in a yet unknown manner, different properties (i.e., hydrophobicity, conformational propensity, polarizability, and hydrogen bonding capability) into the 20 standard natural amino acids, thus making difficult, if not impossible, to univocally relate the change in protein stability or function to the alteration of physicochemical properties caused by amino acid exchange(s). In this view, incorporation of noncoded amino acids with tailored side chains, allowing to finely tune the structure at a protein site, would facilitate to dissect the effects of a given mutation in terms of one or a few physicochemical properties, thus much expanding the scope of physical organic chemistry in the study of proteins. In this review, relevant applications from our laboratory will be presented on the use of noncoded amino acids in structure-activity relationships studies of hirudin binding to thrombin. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Utilization of acidic α-amino acids as acyl donors: an effective stereo-controllable synthesis of aryl-keto α-amino acids and their derivatives.

PubMed

Wang, Lei; Murai, Yuta; Yoshida, Takuma; Okamoto, Masashi; Tachrim, Zetryana Puteri; Hashidoko, Yasuyuki; Hashimoto, Makoto

2014-05-16

Aryl-keto-containing α-amino acids are of great importance in organic chemistry and biochemistry. They are valuable intermediates for the construction of hydroxyl α-amino acids, nonproteinogenic α-amino acids, as well as other biofunctional components. Friedel-Crafts acylation is an effective method to prepare aryl-keto derivatives. In this review, we summarize the preparation of aryl-keto containing α-amino acids by Friedel-Crafts acylation using acidic α-amino acids as acyl-donors and Lewis acids or Brönsted acids as catalysts.

Na+ Interactions with the Neutral Amino Acid Transporter ASCT1*

PubMed Central

Scopelliti, Amanda J.; Heinzelmann, Germano; Kuyucak, Serdar; Ryan, Renae M.; Vandenberg, Robert J.

2014-01-01

The alanine, serine, cysteine transporters (ASCTs) belong to the solute carrier family 1A (SLC1A), which also includes the excitatory amino acid transporters (EAATs) and the prokaryotic aspartate transporter GltPh. Acidic amino acid transport by the EAATs is coupled to the co-transport of three Na+ ions and one proton, and the counter-transport of one K+ ion. In contrast, neutral amino acid exchange by the ASCTs does not require protons or the counter-transport of K+ ions and the number of Na+ ions required is not well established. One property common to SLC1A family members is a substrate-activated anion conductance. We have investigated the number and location of Na+ ions required by ASCT1 by mutating residues in ASCT1 that correspond to residues in the EAATs and GltPh that are involved in Na+ binding. Mutations to all three proposed Na+ sites influence the binding of substrate and/or Na+, or the rate of substrate exchange. A G422S mutation near the Na2 site reduced Na+ affinity, without affecting the rate of exchange. D467T and D467A mutations in the Na1 site reduce Na+ and substrate affinity and also the rate of substrate exchange. T124A and D380A mutations in the Na3 site selectively reduce the affinity for Na+ and the rate of substrate exchange without affecting substrate affinity. In many of the mutants that reduce the rate of substrate transport the amplitudes of the substrate-activated anion conductances are not substantially affected indicating altered ion dependence for channel activation compared with substrate exchange. PMID:24808181

Toxicity of nickel and silver to Nostoc muscorum: interaction with ascorbic acid, glutathione, and sulfur-containing amino acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rai, L.C.; Raizada, M.

1987-08-01

Exposure of Nostoc muscorum to different concentrations of Ni and Ag brought about reduction in growth, carbon fixation, heterocyst production, and nitrogenase activity and increase in the loss of ions (K+, Na+). In an attempt to ameliorate the toxicity of test metals by ascorbic acid, glutathione, and sulfur-containing amino acids (L-cysteine and L-methionine), it was found that the level of protection by ascorbic acid and glutathione was more for Ag than Ni. However, metal-induced inhibition of growth and carbon fixation was equally ameliorated by methionine. But the level of protection by cysteine was quite different, i.e., 27% for Ni andmore » 22% for Ag. Protection of metal toxicity in N. muscorum by amino acids lends further support to self-detoxifying ability of cyanobacteria because they are known to synthesize all essential amino acids.« less

Studies related to primitive chemistry. A proton and nitrogen-14 nuclear magnetic resonance amino acid and nucleic acid constituents and a and their possible relation to prebiotic

NASA Technical Reports Server (NTRS)

Manatt, S. L.; Cohen, E. A.; Shiller, A. M.; Chan, S. I.

1973-01-01

Preliminary proton nuclear magnetic resonance (NMR) studies were made to determine the applicability of this technique for the study of interactions between monomeric and polymeric amino acids with monomeric nucleic acid bases and nucleotides. Proton NMR results for aqueous solutions (D2O) demonstrated interactions between the bases cytosine and adenine and acidic and aromatic amino acids. Solutions of 5'-AMP admixed with amino acids exhibited more complex behavior but stacking between aromatic rings and destacking at high amino acids concentration was evident. The multisite nature of 5'-AMP was pointed out. Chemical shift changes for adenine and 5'-AMP with three water soluble polypeptides demonstrated that significant interactions exist. It was found that the linewidth-pH profile of each amino acid is unique. It is concluded that NMR techniques can give significant and quantitative data on the association of amino acid and nucleic acid constituents.

Nonprotein Amino Acids in the Murchison Meteorite

PubMed Central

Kvenvolden, Keith A.; Lawless, James G.; Ponnamperuma, Cyril

1971-01-01

Twelve nonprotein amino acids appear to be present in the Murchison meteorite. The identity of eight of them has been conclusively established as N-methylglycine, β-alanine, 2-methylalanine, α-amino-n-butyric acid, β-amino-n-butyric acid, γ-amino-n-butyric acid, isovaline, and pipecolic acid. Tentative evidence is presented for the presence of N-methylalanine, N-ethylglycine, β-aminoisobutyric acid, and norvaline. These amino acids appear to be extraterrestrial in origin and may provide new evidence for the hypothesis of chemical evolution. PMID:16591908

Interactive effects of dietary leucine and isoleucine on growth, blood parameters, and amino acid profile of Japanese flounder Paralichthys olivaceus.

PubMed

Wang, Liping; Han, Yuzhe; Jiang, Zhiqiang; Sun, Menglei; Si, Bin; Chen, Fei; Bao, Ning

2017-10-01

A 60-day feeding trial was conducted to assess the interactions of dietary leucine (Leu) and isoleucine (Ile) on Japanese flounder. Fish of 2.69 ± 0.04 g were fed experimental diets containing two levels of Leu (2.58 and 5.08% of diet) combined with three levels of Ile (1.44, 2.21, and 4.44% of diet), respectively. After the feeding trial, growth, proximate composition, muscle total amino acid profile, blood parameters, mucus lysozyme activity, and stress tolerance to freshwater were measured. Statistically significant (P < 0.05) interactive effects of Leu and Ile were found on growth parameters (final body weight, body weight gain, and special growth rate) of Japanese flounder. Antagonism was discovered in high dietary Leu groups, while stimulatory effects were obtained for increased dietary Ile in low Leu groups. Interactive effects of these two branched-chain amino acids were also found on hepatosomatic index of test fish. In addition, crude lipid content of fish whole body was significantly altered by various diets, with antagonism observed in low dietary Leu groups. Interactive effects also existed in muscle amino acid profiles for low fish meal diets, but no interactive impacts were observed on blood parameters. Furthermore, lysozyme activities and freshwater stress were significantly affected by different diets. And antagonism was found on lysozyme activities in low Leu groups. Moreover, high Leu and high Ile levels of diet significantly altered freshwater stress tolerance of Japanese flounder. These findings suggested that dietary Leu and Ile can effect interactively, and fish fed with diets containing 2.58% Leu with 4.44% Ile and 5.08% Leu with 1.44% Ile showed better growth performance.

Gene expression of amino acid transporter in pigeon (Columbia livia) intestine during post-hatch development and its correlation with amino acid in pigeon milk.

PubMed

Zhang, X Y; Zhang, N N; Wan, X P; Li, L L; Zou, X T

2017-05-01

This study was conducted to evaluate gene expression of the amino acid transporter in post-hatch pigeon small intestine and the association of pigeon milk amino acid with the above transporter's gene expression. A total of 48 pigeon breeding families were randomly allocated to 8 groups of 6 replicates of one parental pigeon pair and 2 squabs. Samples of pigeon milk and duodenum, jejunum, and ileum were collected on d 1, 2, 3, 4, 6, 8, 10, and 14 post hatch. The results showed that levels of crude protein (8.93 to 15.56%) were highest in pigeon milk on an air-dry basis. Amino acid content in pigeon milk remained constant in the first 4 d, declined abruptly at d 6, then increased dramatically from d 8 to 14. There was a significant effect of interaction between age and intestinal segments on those amino acid transporters gene expression. mRNA abundance of ATB0'+, SNAT-2, LAT-4, rBAT, b0'+AT, EAAT-3 and PAT-1 was highest in the ileum; B0AT1, asc-1, and IMINO were predominate in the jejunum; and CAT-1 and y+LAT2 were greatest in the duodenum. Age-related changes of amino acid transporter mRNA was inconsistent. mRNA levels of SNAT-2, rBAT, y+LAT2, b0'+AT, and EAAT-3 ascended with age, whereas that of asc-1, CAT-1, and IMINO diminished significantly. Levels of B0AT1 and PAT-1 mRNA abundance were minimized at d 6. However, few correlations were found between pigeon milk amino acid and the amino acid transporter gene expressions in squab small intestine. Our findings provide a comprehensive elaboration on ontogeny of the amino acid transporter in post-hatch pigeon intestine. © 2016 Poultry Science Association Inc.

Urinary amino acid analysis: a comparison of iTRAQ-LC-MS/MS, GC-MS, and amino acid analyzer.

PubMed

Kaspar, Hannelore; Dettmer, Katja; Chan, Queenie; Daniels, Scott; Nimkar, Subodh; Daviglus, Martha L; Stamler, Jeremiah; Elliott, Paul; Oefner, Peter J

2009-07-01

Urinary amino acid analysis is typically done by cation-exchange chromatography followed by post-column derivatization with ninhydrin and UV detection. This method lacks throughput and specificity. Two recently introduced stable isotope ratio mass spectrometric methods promise to overcome those shortcomings. Using two blinded sets of urine replicates and a certified amino acid standard, we compared the precision and accuracy of gas chromatography/mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) of propyl chloroformate and iTRAQ derivatized amino acids, respectively, to conventional amino acid analysis. The GC-MS method builds on the direct derivatization of amino acids in diluted urine with propyl chloroformate, GC separation and mass spectrometric quantification of derivatives using stable isotope labeled standards. The LC-MS/MS method requires prior urinary protein precipitation followed by labeling of urinary and standard amino acids with iTRAQ tags containing different cleavable reporter ions distinguishable by MS/MS fragmentation. Means and standard deviations of percent technical error (%TE) computed for 20 amino acids determined by amino acid analyzer, GC-MS, and iTRAQ-LC-MS/MS analyses of 33 duplicate and triplicate urine specimens were 7.27+/-5.22, 21.18+/-10.94, and 18.34+/-14.67, respectively. Corresponding values for 13 amino acids determined in a second batch of 144 urine specimens measured in duplicate or triplicate were 8.39+/-5.35, 6.23+/-3.84, and 35.37+/-29.42. Both GC-MS and iTRAQ-LC-MS/MS are suited for high-throughput amino acid analysis, with the former offering at present higher reproducibility and completely automated sample pretreatment, while the latter covers more amino acids and related amines.

Stacking and T-shape competition in aromatic-aromatic amino acid interactions.

PubMed

Chelli, Riccardo; Gervasio, Francesco Luigi; Procacci, Piero; Schettino, Vincenzo

2002-05-29

The potential of mean force of interacting aromatic amino acids is calculated using molecular dynamics simulations. The free energy surface is determined in order to study stacking and T-shape competition for phenylalanine-phenylalanine (Phe-Phe), phenylalanine-tyrosine (Phe-Tyr), and tyrosine-tyrosine (Tyr-Tyr) complexes in vacuo, water, carbon tetrachloride, and methanol. Stacked structures are favored in all solvents with the exception of the Tyr-Tyr complex in carbon tetrachloride, where T-shaped structures are also important. The effect of anchoring the two alpha-carbons (C(alpha)) at selected distances is investigated. We find that short and large C(alpha)-C(alpha) distances favor stacked and T-shaped structures, respectively. We analyze a set of 2396 protein structures resolved experimentally. Comparison of theoretical free energies for the complexes to the experimental analogue shows that Tyr-Tyr interaction occurs mainly at the protein surface, while Phe-Tyr and Phe-Phe interactions are more frequent in the hydrophobic protein core. This is confirmed by the Voronoi polyhedron analysis on the database protein structures. As found from the free energy calculation, analysis of the protein database has shown that proximal and distal interacting aromatic residues are predominantly stacked and T-shaped, respectively.

New insights into the metabolism of aspartate-family amino acids in plant seeds.

PubMed

Wang, Wenyi; Xu, Mengyun; Wang, Guoping; Galili, Gad

2018-02-05

Aspartate-family amino acids. Aspartate (Asp)-family pathway, via several metabolic branches, leads to four key essential amino acids: Lys, Met, Thr, and Ile. Among these, Lys and Met have received the most attention, as they are the most limiting amino acid in cereals and legumes crops, respectively. The metabolic pathways of these four essential amino acids and their interactions with regulatory networks have been well characterized. Using this knowledge, extensive efforts have been devoted to augmenting the levels of these amino acids in various plant organs, especially seeds, which serve as the main source of human food and livestock feed. Seeds store a number of storage proteins, which are utilized as nutrient and energy resources. Storage proteins are composed of amino acids, to guarantee the continuation of plant progeny. Thus, understanding the seed metabolism, especially with respect to the accumulation of aspartate-derived amino acids Lys and Met, is a crucial factor for sustainable agriculture. In this review, we summarized the Asp-family pathway, with some new examples of accumulated Asp-family amino acids, particularly Lys and Met, in plant seeds. We also discuss the recent advances in understanding the roles of Asp-family amino acids during seed development.

Differential distribution of amino acids in plants.

PubMed

Kumar, Vinod; Sharma, Anket; Kaur, Ravdeep; Thukral, Ashwani Kumar; Bhardwaj, Renu; Ahmad, Parvaiz

2017-05-01

Plants are a rich source of amino acids and their individual abundance in plants is of great significance especially in terms of food. Therefore, it is of utmost necessity to create a database of the relative amino acid contents in plants as reported in literature. Since in most of the cases complete analysis of profiles of amino acids in plants was not reported, the units used and the methods applied and the plant parts used were different, amino acid contents were converted into relative units with respect to lysine for statistical analysis. The most abundant amino acids in plants are glutamic acid and aspartic acid. Pearson's correlation analysis among different amino acids showed that there were no negative correlations between the amino acids. Cluster analysis (CA) applied to relative amino acid contents of different families. Alismataceae, Cyperaceae, Capparaceae and Cactaceae families had close proximity with each other on the basis of their relative amino acid contents. First three components of principal component analysis (PCA) explained 79.5% of the total variance. Factor analysis (FA) explained four main underlying factors for amino acid analysis. Factor-1 accounted for 29.4% of the total variance and had maximum loadings on glycine, isoleucine, leucine, threonine and valine. Factor-2 explained 25.8% of the total variance and had maximum loadings on alanine, aspartic acid, serine and tyrosine. 14.2% of the total variance was explained by factor-3 and had maximum loadings on arginine and histidine. Factor-4 accounted 8.3% of the total variance and had maximum loading on the proline amino acid. The relative content of different amino acids presented in this paper is alanine (1.4), arginine (1.8), asparagine (0.7), aspartic acid (2.4), cysteine (0.5), glutamic acid (2.8), glutamine (0.6), glycine (1.0), histidine (0.5), isoleucine (0.9), leucine (1.7), lysine (1.0), methionine (0.4), phenylalanine (0.9), proline (1.1), serine (1.0), threonine (1

Amino acids-incorporated nanoflowers with an intrinsic peroxidase-like activity

PubMed Central

Wu, Zhuo-Fu; Wang, Zhi; Zhang, Ye; Ma, Ya-Li; He, Cheng-Yan; Li, Heng; Chen, Lei; Huo, Qi-Sheng; Wang, Lei; Li, Zheng-Qiang

2016-01-01

Functional molecules synthesized by self-assembly between inorganic salts and amino acids have attracted much attention in recent years. A simple method is reported here for fabricating hybrid organic–inorganic nanoflowers using copper (II) ions as the inorganic component and natural amino acids as the organic component. The results indicate that the interactions between amino acid and copper ions cause the growth of the nanoflowers composed by C, N, Cu, P and O elements. The Cu ions and Cu(AA)n complexes containing Cu-O bond are present in the nanoflowers. The nanoflowers have flower-like porous structure dominated by the R groups of amino acids with high surface-to-volume ratios, which is beneficial for exerting its peroxidase-like activity depending on Fenton-like reaction mechanism with ABTS and Rhodamine B as the substrates. It is expected that the nanoflowers hold great promise as enzyme mimics for application in the field of biosensor, bioanalysis and biocatalysis. PMID:26926099

Synthesis of new kojic acid based unnatural α-amino acid derivatives.

PubMed

Balakrishna, C; Payili, Nagaraju; Yennam, Satyanarayana; Uma Devi, P; Behera, Manoranjan

2015-11-01

An efficient method for the preparation of kojic acid based α-amino acid derivatives by alkylation of glycinate schiff base with bromokojic acids have been described. Using this method, mono as well as di alkylated kojic acid-amino acid conjugates have been prepared. This is the first synthesis of C-linked kojic acid-amino acid conjugate where kojic acid is directly linked to amino acid through a C-C bond. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nutritional and medicinal aspects of D-amino acids.

PubMed

Friedman, Mendel; Levin, Carol E

2012-05-01

This paper reviews and interprets a method for determining the nutritional value of D-amino acids, D-peptides, and amino acid derivatives using a growth assay in mice fed a synthetic all-amino acid diet. A large number of experiments were carried out in which a molar equivalent of the test compound replaced a nutritionally essential amino acid such as L-lysine (L-Lys), L-methionine (L-Met), L-phenylalanine (L-Phe), and L-tryptophan (L-Trp) as well as the semi-essential amino acids L-cysteine (L-Cys) and L-tyrosine (L-Tyr). The results show wide-ranging variations in the biological utilization of test substances. The method is generally applicable to the determination of the biological utilization and safety of any amino acid derivative as a potential nutritional source of the corresponding L-amino acid. Because the organism is forced to use the D-amino acid or amino acid derivative as the sole source of the essential or semi-essential amino acid being replaced, and because a free amino acid diet allows better control of composition, the use of all-amino-acid diets for such determinations may be preferable to protein-based diets. Also covered are brief summaries of the widely scattered literature on dietary and pharmacological aspects of 27 individual D-amino acids, D-peptides, and isomeric amino acid derivatives and suggested research needs in each of these areas. The described results provide a valuable record and resource for further progress on the multifaceted aspects of D-amino acids in food and biological samples.

Increased Amino Acid Uptake Supports Autophagy-Deficient Cell Survival upon Glutamine Deprivation.

PubMed

Zhang, Nan; Yang, Xin; Yuan, Fengjie; Zhang, Luyao; Wang, Yanan; Wang, Lina; Mao, Zebin; Luo, Jianyuan; Zhang, Hongquan; Zhu, Wei-Guo; Zhao, Ying

2018-06-05

Autophagy is a protein degradation process by which intracellular materials are recycled for energy homeostasis. However, the metabolic status and energy source of autophagy-defective tumor cells are poorly understood. Here, our data show that amino acid uptake from the extracellular environment is increased in autophagy-deficient cells upon glutamine deprivation. This elevated amino acid uptake results from activating transcription factor 4 (ATF4)-dependent upregulation of AAT (amino acid transporter) gene expression. Furthermore, we identify SIRT6, a NAD + -dependent histone deacetylase, as a corepressor of ATF4 transcriptional activity. In autophagy-deficient cells, activated NRF2 enhances ATF4 transcriptional activity by disrupting the interaction between SIRT6 and ATF4. In this way, autophagy-deficient cells exhibit increased AAT expression and show increased amino acid uptake. Notably, inhibition of amino acid uptake reduces the viability of glutamine-deprived autophagy-deficient cells, but not significantly in wild-type cells, suggesting reliance of autophagy-deficient tumor cells on extracellular amino acid uptake. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Prebiotic thermal polymerization of crystals of amino acids via the diketopiperazine reaction.

PubMed

Mosqueira, F G; Ramos-Bernal, S; Negrón-Mendoza, A

2008-01-01

In this work, we continue our studies on the thermal prebiotic oligomerization of amino acids. The next step is to consider all four types of electromagnetic interactions that our model may admit. In addition, only the polymerization of amino acids via the formation of diketopiperazine, which arises from the cyclodehydration of two amino acids, will be considered. By assuming that only one residue group of two will predominate in the diketopiperazine molecule, it is possible to reduce the three-body problem to a simpler situation with the two objects that we have already solved.

Guanidinium/ammonium competition and proton transfer in the interaction of the amino acid arginine with the tetracarboxylic 18-crown-6 ionophore.

PubMed

Avilés-Moreno, Juan Ramón; Berden, Giel; Oomens, Jos; Martínez-Haya, Bruno

2018-02-07

The recognition of arginine plays a central role in modern proteomics and genomics. Arginine is unique among natural amino acids due to the high basicity of its guanidinium side chain, which sustains specific interactions and proton exchange biochemical processes. The search for suitable macrocyclic ionophores constitutes a promising route towards the development of arginine receptors. This study evaluates the conformational features involved in the binding of free arginine by the polyether macrocycle (18-crown-6)-tetracarboxylic acid. Infrared action vibrational spectroscopy and quantum-chemical computations are combined to characterize the complexes with net charges +1 and +2. The spectrum of the +1 complex can be explained in terms of a configuration predominantly stabilized by a robust bidentate coordination of guanidinium with a carboxylate group formed from the deprotonation of one side group of the crown ether. The released proton is transferred to the amino terminus of arginine, which then coordinates with the crown ether ring. In an alternative type of conformation, partly consistent with experiment, the amino terminus is neutral and the guanidinium group inserts into the crown ether cavity. In the +2 complexes, arginine is always doubly protonated and the most stable conformations are characterized by a tripodal coordination of the ammonium -NH 3 + group of arginine with the oxygen atoms of the macrocycle ring, while the interactions of the amino acid with the side carboxylic acid groups of the crown ether acquire a remarkable lesser role.

Amino Acid Properties Conserved in Molecular Evolution

PubMed Central

Rudnicki, Witold R.; Mroczek, Teresa; Cudek, Paweł

2014-01-01

That amino acid properties are responsible for the way protein molecules evolve is natural and is also reasonably well supported both by the structure of the genetic code and, to a large extent, by the experimental measures of the amino acid similarity. Nevertheless, there remains a significant gap between observed similarity matrices and their reconstructions from amino acid properties. Therefore, we introduce a simple theoretical model of amino acid similarity matrices, which allows splitting the matrix into two parts – one that depends only on mutabilities of amino acids and another that depends on pairwise similarities between them. Then the new synthetic amino acid properties are derived from the pairwise similarities and used to reconstruct similarity matrices covering a wide range of information entropies. Our model allows us to explain up to 94% of the variability in the BLOSUM family of the amino acids similarity matrices in terms of amino acid properties. The new properties derived from amino acid similarity matrices correlate highly with properties known to be important for molecular evolution such as hydrophobicity, size, shape and charge of amino acids. This result closes the gap in our understanding of the influence of amino acids on evolution at the molecular level. The methods were applied to the single family of similarity matrices used often in general sequence homology searches, but it is general and can be used also for more specific matrices. The new synthetic properties can be used in analyzes of protein sequences in various biological applications. PMID:24967708

Topology of RNA–protein nucleobase–amino acid π–π interactions and comparison to analogous DNA–protein π–π contacts

PubMed Central

Wilson, Katie A.; Holland, Devany J.; Wetmore, Stacey D.

2016-01-01

The present work analyzed 120 high-resolution X-ray crystal structures and identified 335 RNA–protein π-interactions (154 nonredundant) between a nucleobase and aromatic (W, H, F, or Y) or acyclic (R, E, or D) π-containing amino acid. Each contact was critically analyzed (including using a visual inspection protocol) to determine the most prevalent composition, structure, and strength of π-interactions at RNA–protein interfaces. These contacts most commonly involve F and U, with U:F interactions comprising one-fifth of the total number of contacts found. Furthermore, the RNA and protein π-systems adopt many different relative orientations, although there is a preference for more parallel (stacked) arrangements. Due to the variation in structure, the strength of the intermolecular forces between the RNA and protein components (as determined from accurate quantum chemical calculations) exhibits a significant range, with most of the contacts providing significant stability to the associated RNA–protein complex (up to −65 kJ mol−1). Comparison to the analogous DNA–protein π-interactions emphasizes differences in RNA– and DNA–protein π-interactions at the molecular level, including the greater abundance of RNA contacts and the involvement of different nucleobase/amino acid residues. Overall, our results provide a clearer picture of the molecular basis of nucleic acid–protein binding and underscore the important role of these contacts in biology, including the significant contribution of π–π interactions to the stability of nucleic acid–protein complexes. Nevertheless, more work is still needed in this area in order to further appreciate the properties and roles of RNA nucleobase–amino acid π-interactions in nature. PMID:26979279

Improving protein complex classification accuracy using amino acid composition profile.

PubMed

Huang, Chien-Hung; Chou, Szu-Yu; Ng, Ka-Lok

2013-09-01

Protein complex prediction approaches are based on the assumptions that complexes have dense protein-protein interactions and high functional similarity between their subunits. We investigated those assumptions by studying the subunits' interaction topology, sequence similarity and molecular function for human and yeast protein complexes. Inclusion of amino acids' physicochemical properties can provide better understanding of protein complex properties. Principal component analysis is carried out to determine the major features. Adopting amino acid composition profile information with the SVM classifier serves as an effective post-processing step for complexes classification. Improvement is based on primary sequence information only, which is easy to obtain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Urinary Amino Acid Analysis: A Comparison of iTRAQ®-LC-MS/MS, GC-MS, and Amino Acid Analyzer

PubMed Central

Kaspar, Hannelore; Dettmer, Katja; Chan, Queenie; Daniels, Scott; Nimkar, Subodh; Daviglus, Martha L.; Stamler, Jeremiah; Elliott, Paul; Oefner, Peter J.

2009-01-01

Urinary amino acid analysis is typically done by cation-exchange chromatography followed by post-column derivatization with ninhydrin and UV detection. This method lacks throughput and specificity. Two recently introduced stable isotope ratio mass spectrometric methods promise to overcome those shortcomings. Using two blinded sets of urine replicates and a certified amino acid standard, we compared the precision and accuracy of gas chromatography/mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) of propyl chloroformate and iTRAQ® derivatized amino acids, respectively, to conventional amino acid analysis. The GC-MS method builds on the direct derivatization of amino acids in diluted urine with propyl chloroformate, GC separation and mass spectrometric quantification of derivatives using stable isotope labeled standards. The LC-MS/MS method requires prior urinary protein precipitation followed by labeling of urinary and standard amino acids with iTRAQ® tags containing different cleavable reporter ions distinguishable by MS/MS fragmentation. Means and standard deviations of percent technical error (%TE) computed for 20 amino acids determined by amino acid analyzer, GC-MS, and iTRAQ®-LC-MS/MS analyses of 33 duplicate and triplicate urine specimens were 7.27±5.22, 21.18±10.94, and 18.34±14.67, respectively. Corresponding values for 13 amino acids determined in a second batch of 144 urine specimens measured in duplicate or triplicate were 8.39±5.35, 6.23±3.84, and 35.37±29.42. Both GC-MS and iTRAQ®-LC-MS/MS are suited for high-throughput amino acid analysis, with the former offering at present higher reproducibility and completely automated sample pretreatment, while the latter covers more amino acids and related amines. PMID:19481989

Molecular characteristics of mammalian and insect amino acid transporters: implications for amino acid homeostasis.

PubMed

Castagna, M; Shayakul, C; Trotti, D; Sacchi, V F; Harvey, W R; Hediger, M A

1997-01-01

In mammalian cells, the uptake of amino acids is mediated by specialized, energy-dependent and passive transporters with overlapping substrate specificities. Most energy-dependent transporters are coupled either to the cotransport of Na+ or Cl- or to the countertransport of K+. Passive transporters are either facilitated transporters or channels. As a prelude to the molecular characterization of the different classes of transporters, we have isolated transporter cDNAs by expression-cloning with Xenopus laevis oocytes and we have characterized the cloned transporters functionally by uptake studies into oocytes using radiolabelled substrates and by electrophysiology to determine substrate-evoked currents. Mammalian transporters investigated include the dibasic and neutral amino acid transport protein D2/NBAT (system b0+) and the Na(+)- and K(+)-dependent neuronal and epithelial high-affinity glutamate transporter EAAC1 (system XAG-). A detailed characterization of these proteins has provided new information on transport characteristics and mechanisms for coupling to different inorganic ions. This work has furthermore advanced our understanding of the roles these transporters play in amino acid homeostasis and in various pathologies. For example, in the central nervous system, glutamate transporters are critically important in maintaining the extracellular glutamate concentration below neurotoxic levels, and defects of the human D2 gene have been shown to account for the formation of kidney stones in patients with cystinuria. Using similar approaches, we are investigating the molecular characteristics of K(+)-coupled amino acid transporters in the larval lepidopteran insect midgut. In the larval midgut, K+ is actively secreted into the lumen through the concerted action of an apical H+ V-ATPase and an apical K+/2H+ antiporter, thereby providing the driving force for absorption of amino acids. In vivo, the uptake occurs at extremely high pH (pH 10) and is driven by a

Human Protein and Amino Acid Requirements.

PubMed

Hoffer, L John

2016-05-01

Human protein and amino acid nutrition encompasses a wide, complex, frequently misunderstood, and often contentious area of clinical research and practice. This tutorial explains the basic biochemical and physiologic principles that underlie our current understanding of protein and amino acid nutrition. The following topics are discussed: (1) the identity, measurement, and essentiality of nutritional proteins; (2) the definition and determination of minimum requirements; (3) nutrition adaptation; (4) obligatory nitrogen excretion and the minimum protein requirement; (5) minimum versus optimum protein intakes; (6) metabolic responses to surfeit and deficient protein intakes; (7) body composition and protein requirements; (8) labile protein; (9) N balance; (10) the principles of protein and amino acid turnover, including an analysis of the controversial indicator amino acid oxidation technique; (11) general guidelines for evaluating protein turnover articles; (12) amino acid turnover versus clearance; (13) the protein content of hydrated amino acid solutions; (14) protein requirements in special situations, including protein-catabolic critical illness; (15) amino acid supplements and additives, including monosodium glutamate and glutamine; and (16) a perspective on the future of protein and amino acid nutrition research. In addition to providing practical information, this tutorial aims to demonstrate the importance of rigorous physiologic reasoning, stimulate intellectual curiosity, and encourage fresh ideas in this dynamic area of human nutrition. In general, references are provided only for topics that are not well covered in modern textbooks. © 2016 American Society for Parenteral and Enteral Nutrition.

Amino Acid Transporters and Release of Hydrophobic Amino Acids in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120.

PubMed

Pernil, Rafael; Picossi, Silvia; Herrero, Antonia; Flores, Enrique; Mariscal, Vicente

2015-04-23

Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that can use inorganic compounds such as nitrate or ammonium as nitrogen sources. In the absence of combined nitrogen, it can fix N2 in differentiated cells called heterocysts. Anabaena also shows substantial activities of amino acid uptake, and three ABC-type transporters for amino acids have been previously characterized. Seven new loci encoding predicted amino acid transporters were identified in the Anabaena genomic sequence and inactivated. Two of them were involved in amino acid uptake. Locus alr2535-alr2541 encodes the elements of a hydrophobic amino acid ABC-type transporter that is mainly involved in the uptake of glycine. ORF all0342 encodes a putative transporter from the dicarboxylate/amino acid:cation symporter (DAACS) family whose inactivation resulted in an increased uptake of a broad range of amino acids. An assay to study amino acid release from Anabaena filaments to the external medium was set up. Net release of the alanine analogue α-aminoisobutyric acid (AIB) was observed when transport system N-I (a hydrophobic amino acid ABC-type transporter) was engaged in the uptake of a specific substrate. The rate of AIB release was directly proportional to the intracellular AIB concentration, suggesting leakage from the cells by diffusion.

Amino Acid Crossword Puzzle

ERIC Educational Resources Information Center

Sims, Paul A.

2011-01-01

Learning the 20 standard amino acids is an essential component of an introductory course in biochemistry. Later in the course, the students study metabolism and learn about various catabolic and anabolic pathways involving amino acids. Learning new material or concepts often is easier if one can connect the new material to what one already knows;…

Multipolar Electrostatic Energy Prediction for all 20 Natural Amino Acids Using Kriging Machine Learning.

PubMed

Fletcher, Timothy L; Popelier, Paul L A

2016-06-14

A machine learning method called kriging is applied to the set of all 20 naturally occurring amino acids. Kriging models are built that predict electrostatic multipole moments for all topological atoms in any amino acid based on molecular geometry only. These models then predict molecular electrostatic interaction energies. On the basis of 200 unseen test geometries for each amino acid, no amino acid shows a mean prediction error above 5.3 kJ mol(-1), while the lowest error observed is 2.8 kJ mol(-1). The mean error across the entire set is only 4.2 kJ mol(-1) (or 1 kcal mol(-1)). Charged systems are created by protonating or deprotonating selected amino acids, and these show no significant deviation in prediction error over their neutral counterparts. Similarly, the proposed methodology can also handle amino acids with aromatic side chains, without the need for modification. Thus, we present a generic method capable of accurately capturing multipolar polarizable electrostatics in amino acids.

Amino acid composition of some Mexican foods.

PubMed

Morales de León, Josefina; Camacho, M Elena; Bourges, Héctor

2005-06-01

Knowledge of the amino acid composition of foods is essential to calculate their chemical score, which is used to predict protein quality of foods and diets. Though amino acid composition of many foods is reasonably well established, better knowledge is needed on native foods consumed in different regions and countries. This paper presents the amino acid composition of different presentations of raw and processed foods produced and consumed in Mexico. The amino acid composition was determined using Beckman amino acid analyzers (models 116 and 6300). Tryptophan was determined using the Spies and Chambers method. Of the different foods analyzed, some comments are made on native or basic foods in Mexico: Spirulin, where lysine is the limiting amino acid, with a chemical score of 67%, is a good source of tryptophan (1.16g/16 gN); amaranth contains high levels of sulphur amino acids (4.09 to 5.34 g/16gN), with a protein content of 15 g/100g; and pulque, a Pre-Hispanic beverage that contains high levels of tryptophan (2.58 g/16 gN) and sulphur amino acids (2.72 g/16 gN). Finally, insects are good sources of sulphur amino acids and lysine.

Present Global Situation of Amino Acids in Industry.

PubMed

Tonouchi, Naoto; Ito, Hisao

At present, amino acids are widely produced and utilized industrially. Initially, monosodium glutamate (MSG) was produced by extraction from a gluten hydrolysate. The amino acid industry started using the residual of the lysate. The discovery of the functions of amino acids has led to the expansion of their field of use. In addition to seasoning and other food use, amino acids are used in many fields such as animal nutrients, pharmaceuticals, and cosmetics. On the other hand, the invention of the glutamate fermentation process, followed by the development of fermentation methods for many other amino acids, is no less important. The supply of these amino acids at a low price is very essential for their industrial use. Most amino acids are now produced by fermentation. The consumption of many amino acids such as MSG or feed-use amino acids is still rapidly increasing.

Enantiomer-specific selection of amino acids.

PubMed

Ren, Xueying; Tellez, Luis A; de Araujo, Ivan E

2013-12-01

Dietary intake of L-amino acids impacts on several physiological functions, including the control of gastrointestinal motility, pancreatic secretion, and appetite. However, the biological mechanisms regulating behavioral predilections for certain amino acid types remain poorly understood. We tested the hypothesis that, in mice, the potency with which a given glucogenic amino acid increases glucose utilization reflects its rewarding properties. We have found that: (1) during long-, but not short-, term preference tests, L-alanine and L-serine were preferred over their D-enantiomer counterparts, while no such effect was observed for L-threonine vs. D-threonine; (2) these behavioral patterns were closely associated with the ability of L-amino acids to promote increases in respiratory exchange ratios such that those, and only those, L-amino acids able to promote increases in respiratory exchange ratios were preferred over their D-isomers; (3) these behavioral preferences were independent of gustatory influences, since taste-deficient Trpm5 knockout mice displayed ingestive responses very similar to those of their wild-type counterparts. We conclude that the ability to promote increases in respiratory exchange ratios enhances the reward value of nutritionally relevant amino acids and suggest a mechanistic link between substrate utilization and amino acid preferences.

Enantiomer-specific selection of amino acids

PubMed Central

Ren, Xueying; Tellez, Luis A; de Araujo, Ivan E

2013-01-01

Dietary intake of L-amino acids impacts on several physiological functions, including the control of gastrointestinal motility, pancreatic secretion, and appetite. However, the biological mechanisms regulating behavioral predilections for certain amino acid types remain poorly understood. We tested the hypothesis that, in mice, the potency with which a given glucogenic amino acid increases glucose utilization reflects its rewarding properties. We have found that: 1. During long-, but not short-, term preference tests, L-alanine and L-serine were preferred over their D-enantiomer counterparts, while no such effect was observed for L-threonine vs. D-threonine; 2. These behavioral patterns were closely associated with the ability of L-amino acids to promote increases in respiratory exchange ratios such that those, and only those, L-amino acids able to promote increases in respiratory exchange ratios were preferred over their D-isomers; 3. These behavioral preferences were independent of gustatory influences, since taste-deficient Trpm5 knockout mice displayed ingestive responses very similar to those of their wild-type counterparts. We conclude that the ability to promote increases in respiratory exchange ratios enhances the reward value of nutritionally relevant amino acids, and suggest a mechanistic link between substrate utilization and amino acid preferences. PMID:24072505

Novel families of vacuolar amino acid transporters.

PubMed

Sekito, Takayuki; Fujiki, Yuki; Ohsumi, Yoshinori; Kakinuma, Yoshimi

2008-08-01

Amino acids are compartmentalized in the vacuoles of microorganisms and plants. In Saccharomyces cerevisiae, basic amino acids accumulate preferentially into vacuoles but acidic amino acids are almost excluded from them. This indicates that selective machineries operate at the vacuolar membrane. The members of the amino acid/auxin permease family and the major facilitator superfamily involved in the vacuolar compartmentalization of amino acids have been recently identified in studies using S. cerevisiae. Homologous genes for these transporters are also found in plant and mammalian genomes. The physiological significance in response to nitrogen starvation can now be discussed. (c) 2008 IUBMB

Mutual Exclusion of Urea and Trimethylamine N-oxide from Amino Acids in Mixed Solvent Environment

NASA Astrophysics Data System (ADS)

Ganguly, Pritam; Hajari, Timir; Shea, Joan-Emma; van der Vegt, Nico F. A.

2015-03-01

We study the solvation thermodynamics of individual amino acids in mixed urea and trimethylamine N-oxide (TMAO) solutions using molecular dynamics simulations and the Kirkwood-Buff theory. Our results on the preferential interactions between the amino acids and the cosolvents (urea and TMAO) show a mutual exclusion of both the cosolvents from the amino acid surface in the mixed cosolvent condition which is followed by an increase in the cosolvent-cosolvent aggregation away from the amino acid surface. The effects of the mixed cosolvents on the association of the amino acids and the preferential solvation of the amino acids by water are found to be highly non-linear in terms of the effects of the individual cosolvents. A similar result has been found for the association of the protein backbone, mimicked by triglycine. Our results have been confirmed by different TMAO force-fields and the mutual exclusions of the cosolvents from the amino acids are found to be independent of the choice of the strength of the TMAO-water interactions. Based on our data, a general mechanism can potentially be proposed for the effects of the mixed cosolvents on the preferential solvations of the solutes including the case of cononsolvency.

40 CFR 721.1705 - Benzoic acid, 3-amino-, diazotized, coupled with 6-amino-4-hydroxy-2-naphthalenesulfonic acid...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzoic acid, 3-amino-, diazotized, coupled with 6-amino-4-hydroxy-2-naphthalenesulfonic acid, diazotized, (3-aminophenyl)phosphonic acid and... Significant New Uses for Specific Chemical Substances § 721.1705 Benzoic acid, 3-amino-, diazotized, coupled...

40 CFR 721.1705 - Benzoic acid, 3-amino-, diazotized, coupled with 6-amino-4-hydroxy-2-naphthalenesulfonic acid...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzoic acid, 3-amino-, diazotized, coupled with 6-amino-4-hydroxy-2-naphthalenesulfonic acid, diazotized, (3-aminophenyl)phosphonic acid and... Significant New Uses for Specific Chemical Substances § 721.1705 Benzoic acid, 3-amino-, diazotized, coupled...

Identification of amino acids in the human tetherin transmembrane domain responsible for HIV-1 Vpu interaction and susceptibility.

PubMed

Kobayashi, Tomoko; Ode, Hirotaka; Yoshida, Takeshi; Sato, Kei; Gee, Peter; Yamamoto, Seiji P; Ebina, Hirotaka; Strebel, Klaus; Sato, Hironori; Koyanagi, Yoshio

2011-01-01

Tetherin, also known as BST-2/CD317/HM1.24, is an antiviral cellular protein that inhibits the release of HIV-1 particles from infected cells. HIV-1 viral protein U (Vpu) is a specific antagonist of human tetherin that might contribute to the high virulence of HIV-1. In this study, we show that three amino acid residues (I34, L37, and L41) in the transmembrane (TM) domain of human tetherin are critical for the interaction with Vpu by using a live cell-based assay. We also found that the conservation of an additional amino acid at position 45 and two residues downstream of position 22, which are absent from monkey tetherins, are required for the antagonism by Vpu. Moreover, computer-assisted structural modeling and mutagenesis studies suggest that an alignment of these four amino acid residues (I34, L37, L41, and T45) on the same helical face in the TM domain is crucial for the Vpu-mediated antagonism of human tetherin. These results contribute to the molecular understanding of human tetherin-specific antagonism by HIV-1 Vpu.

Free amino acids in spider hemolymph.

PubMed

Tillinghast, Edward K; Townley, Mark A

2008-11-01

We examined the free amino acid composition of hemolymph from representatives of five spider families with an interest in knowing if the amino acid profile in the hemolymph of orb-web-building spiders reflects the high demands for small organic compounds in the sticky droplets of their webs. In nearly all analyses, on both orb and non-orb builders, glutamine was the most abundant free amino acid. Glycine, taurine, proline, histidine, and alanine also tended to be well-represented in orb and non-orb builders. While indications of taxon-specific differences in amino acid composition were observed, it was not apparent that two presumptive precursors (glutamine, taurine) of orb web sticky droplet compounds were uniquely enriched in araneids (orb builders). However, total amino acid concentrations were invariably highest in the araneids and especially so in overwintering juveniles, even as several of the essential amino acids declined during this winter diapause. Comparing the data from this study with those from earlier studies revealed a number of discrepancies. The possible origins of these differences are discussed.

A reexamination of amino acids in lunar soil

NASA Technical Reports Server (NTRS)

Brinton, K. L. F.; Bada, J. L.; Arnold, J. R.

1993-01-01

Amino acids in lunar soils provide an important indicator of the level of prebiotic organic compounds on the moon. The results provide insight into the chemistry of amino acid precursors, and furthermore, given the flux of carbonaceous material to the moon, we can evaluate the survival of organics upon impact. The amino acid contents of both hydrolyzed and unhydrolyzed hot-water extracts of Apollo 17 lunar soil were determined using ophthaldialdehyde/N-acetyl cysteine (OPA/NAC) derivatization followed by HPLC analysis. Previous studies of lunar amino acids were inconclusive, as the technique used (derivatization with ninhydrin followed by HPLC analysis) was unable to discriminate between cosmogenic amino acids and terrestrial contaminants. Cosmogenic amino acids are racemic, and many of the amino acids found in carbonaceous meteorites such as Murchison, i.e., alpha-amino-i-butyric acid (aib), are extremely rare on Earth. The ninhydrin method does not distinguish amino acid enantiomers, nor does it detect alpha-alkyl amino acids such as aib, whereas the OPA/NAC technique does both.

Hormone regulation of rhizome development in tall fescue (Festuca arundinacea) associated with proteomic changes controlling respiratory and amino acid metabolism

PubMed Central

Ma, Xiqing; Xu, Qian; Meyer, William A.; Huang, Bingru

2016-01-01

Background and Aims Rhizomes are underground stems with meristematic tissues capable of generating shoots and roots. However, mechanisms controlling rhizome formation and growth are yet to be completely understood. The objectives of this study were to investigate whether rhizome development could be regulated by cytokinins (CKs) and gibberellic acids (GAs), and determine underlying mechanisms of regulation of rhizome formation and growth of tall fescue (Festuca arundinacea) by a CK or GA through proteomic and transcript analysis. Methods A rhizomatous genotype of tall fescue (‘BR’) plants were treated with 6-benzylaminopurine (BAP, a synthetic cytokinin) or GA3 in hydroponic culture in growth chambers. Furthermore, comparative proteomic analysis of two-dimensional electrophoresis and mass spectrometry were performed to investigate proteins and associated metabolic pathways imparting increased rhizome number by BAP and rhizome elongation by GA3. Key Results BAP stimulated rhizome formation while GA3 promoted rhizome elongation. Proteomic analysis identified 76 differentially expressed proteins (DEPs) due to BAP treatment and 37 DEPs due to GA3 treatment. Cytokinin-related genes and cell division-related genes were upregulated in the rhizome node by BAP and gibberellin-related and cell growth-related genes in the rhizome by GA3. Conclusions Most of the BAP- or GA-responsive DEPs were involved in respiratory metabolism and amino acid metabolism. Transcription analysis demonstrated that genes involved in hormone metabolism, signalling pathways, cell division and cell-wall loosening were upregulated by BAP or GA3. The CK and GA promoted rhizome formation and growth, respectively, by activating metabolic pathways that supply energy and amino acids to support cell division and expansion during rhizome initiation and elongation in tall fescue. PMID:27443301

Enterobacter sp. I-3, a bio-herbicide inhibits gibberellins biosynthetic pathway and regulates abscisic acid and amino acids synthesis to control plant growth.

PubMed

Radhakrishnan, Ramalingam; Park, Jae-Man; Lee, In-Jung

2016-12-01

Very few bacterial species were identified as bio-herbicides for weed control. The present research was focused to elucidate the plant growth retardant properties of Enterobacter sp. I-3 during their interaction by determining the changes in endogenous photosynthetic pigments, plant hormones and amino acids. The two bacterial isolates I-4-5 and I-3 were used to select the superior bacterium for controlling weed seeds (Echinochloa crus-galli L. and Portulaca oleracea L.) germination. The post-inoculation of I-3 (Enterobacter sp. I-3) significantly inhibited the weeds seed germination than their controls. The mechanism of bacterium induced plant growth reduction was identified in lettuce treated with I-3 bacterium and compared their effects with known chemical herbicide, trinexapac-ethyl (TE). The treatment of I-3 and TE showed a significant inhibitory effect on shoot length, leaf number, leaf length, leaf width, shoot weight, root weight and chlorophyll content in lettuce seedlings. The endogenous gibberellins (GAs) and abscisic acid (ABA) analysis showed that Enterobacter sp. I-3 treated plants had lower levels of GAs (GA 12 , GA 19 , GA 20 and GA 8 ) and GAs/ABA ratio and then, the higher level of ABA when compared to their controls. Indeed, the individual amino acids ie., aspartic acid, glutamic acid, glycine, threonine, alanine, serine, leucine, isoleucine and tyrosine were declined in TE and I-3 exposed plants. Our results suggest that the utilization of Enterobacter sp. I-3 inhibits the GAs pathway and amino acids synthesis in weeds to control their growth can be an alternative to chemical herbicides. Copyright © 2016 Elsevier GmbH. All rights reserved.

Extraterrestrial Amino Acids in the Almahata Sitta Meteorite

NASA Technical Reports Server (NTRS)

Glavin, Daniel P.; Aubrey, Andrew D.; Callahan, Michael P.; Dworkin, Jason P.; Elsila, Jamie E.; Parker, Eric T.; Bada, Jeffrey L.

2010-01-01

Amino acid analysis of a meteorite fragment of asteroid 2008 TC3 called Almahata Sitta was carried out using reverse-phase liquid chromatography coupled with UV fluorescence detection and time-of-flight mass spectrometry (LC-FD/ToF-MS) as part of a sample analysis consortium. LC-FD/ToF-MS analyses of hot-water extracts from the meteorite revealed a complex distribution of two- to seven-carbon aliphatic amino acids and one- to three-carbon amines with abundances ranging from 0.5 to 149 parts-per-billion (ppb). The enantiomeric ratios of the amino acids alanine, R-amino-n-butyric acid (beta-ABA), 2-amino-2-methylbutanoic acid (isovaline), and 2-aminopentanoic acid (norvaline) in the meteorite were racemic (D/L approximately 1), indicating that these amino acids are indigenous to the meteorite and not terrestrial contaminants. Several other non-protein amino acids were also identified in the meteorite above background levels including alpha-aminoisobutyric acid (alpha-AIB), 4-amino-2- methylbutanoic acid, 4-amino-3-methylbutanoic acid, and 3-, 4-, and 5-aminopentanoic acid. The total abundances of isovaline and alpha-AIB in Almahata Sitta are 1000 times lower than the abundances of these amino acids found in the CM carbonaceous chondrite Murchison. The extremely low abundances and unusual distribution of five carbon amino acids in Almahata Sitta compared to Cl, CM, and CR carbonaceous chondrites may reflect extensive thermal alteration of amino acids on the parent asteroid by partial melting during formation or subsequent impact shock heating. It is also possible that amino acids were synthesized by catalytic reactions on the parent body after asteroid 2008 TC3 cooled to lower temperatures.

Amino Acid Stability in the Early Oceans

NASA Technical Reports Server (NTRS)

Parker, E. T.; Brinton, K. L.; Burton, A. S.; Glavin, D. P.; Dworkin, J. P.; Bada, J. L.

2015-01-01

It is likely that a variety of amino acids existed in the early oceans of the Earth at the time of the origin and early evolution of life. "Primordial soup", hydrothermal vent, and meteorite based processes could have contributed to such an inventory. Several "protein" amino acids were likely present, however, based on prebiotic synthesis experiments and carbonaceous meteorite studies, non-protein amino acids, which are rare on Earth today, were likely the most abundant. An important uncertainty is the length of time these amino acids could have persisted before their destruction by abiotic and biotic processes. Prior to life, amino acid concentrations in the oceans were likely regulated by circulation through hydro-thermal vents. Today, the entire ocean circulates through vent systems every 10(exp 7) years. On the early Earth, this value was likely smaller due to higher heat flow and thus marine amino acid life-time would have been shorter. After life, amino acids in the oceans could have been assimilated by primitive organisms.

Characterizing amino-acid biosignatures amongst individuals with schizophrenia: a case-control study.

PubMed

Cao, Bing; Wang, Dongfang; Brietzke, Elisa; McIntyre, Roger S; Pan, Zihang; Cha, Danielle; Rosenblat, Joshua D; Zuckerman, Hannah; Liu, Yaqiong; Xie, Qing; Wang, Jingyu

2018-05-23

Amino acids and derivatives participate in the biosynthesis and downstream effects of numerous neurotransmitters. Variations in specific amino acids have been implicated in the pathophysiology of schizophrenia. Herein, we sought to compare levels of amino acids and derivatives between subjects with schizophrenia and healthy controls (HC). Two hundred and eight subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria (DSM-IV)-defined schizophrenia and 175 age- and sex-matched HC were enrolled. The levels of twenty-five amino acids and seven related derivatives were measured in plasma samples using hydrophilic interaction liquid chromatography (HILIC) liquid chromatography-tandem mass spectrometry (LC-MS). After controlling for age, sex and body mass index (BMI), four amino acids and derivatives (i.e., cysteine, GABA, glutamine and sarcosine) were observed to be higher in the schizophrenia group when compared with HC; seven amino acids and derivatives were lower in the schizophrenia group (i.e., arginine, L-ornithine, threonine, taurine, tryptophan, methylcysteine, and kynurenine). Statistically significant differences in plasma amino-acid profiles between subjects with first-episode vs. recurrent schizophrenia for aspartate and glutamine were also demonstrated using generalized linear models controlling for age, sex, and BMI. The differences in amino acids and derivatives among individuals with schizophrenia when compared to HC may represent underlying pathophysiology, including but not limited to dysfunctional proteinogenic processes, alterations in excitatory and inhibitory neurotransmission, changes in ammonia metabolism and the urea cycle. Taken together, amino-acid profiling may provide a novel stratification approach among individuals with schizophrenia.

Optical Sensors for Detection of Amino Acids.

PubMed

Pettiwala, Aafrin M; Singh, Prabhat K

2017-11-06

Amino acids are crucially involved in a myriad of biological processes. Any aberrant changes in physiological level of amino acids often manifest in common metabolic disorders, serious neurological conditions and cardiovascular diseases. Thus, devising methods for detection of trace amounts of amino acids becomes highly elemental to their efficient clinical diagnosis. Recently, the domain of developing optical sensors for detection of amino acids has witnessed significant activity which is the focus of the current review article. We undertook a detailed search of the peer-reviewed literature that primarily deals with optical sensors for amino acids and focuses on the use of different type of materials as a sensing platform. Ninety-five papers have been included in the review, majority of which deals with optical sensors. We attempt to systematically classify these contributions based on applications of various chemical and biological scaffolds such as polymers, supramolecular assemblies, nanoparticles, DNA, heparin etc. for the sensing of amino acids. This review identifies that supramolecular assemblies and nanomaterial continue to be commonly used materials to devise sensors for amino acids followed by surfactant assemblies. The broad implications of amino acids in human health and diagnosis have stirred a lot of interest to develop optimized optical detection systems for amino acids in recent years, using different materials based on chemical and biological scaffolds. We have also attempted to highlight the merits and demerits of some of the noteworthy sensor systems to instigate further efforts for constructing amino acids sensor based on unconventional concepts. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Amino acids in the Tagish Lake Meteorite

NASA Technical Reports Server (NTRS)

Kminek, G.; Botta, O.; Glavin, D. P.; Bada, J. L.

2002-01-01

High-performance liquid chromatography (HPLC) based amino acid analysis of a Tagish Lake meteorite sample recovered 3 months after the meteorite fell to Earth have revealed that the amino acid composition of Tagish Lake is strikingly different from that of the CM and CI carbonaceous chondrites. We found that the Tagish Lake meteorite contains only trace levels of amino acids (total abundance = 880 ppb), which is much lower than the total abundance of amino acids in the CI Orgueil (4100 ppb) and the CM Murchison (16 900 ppb). Because most of the same amino acids found in the Tagish Lake meteorite are also present in the Tagish Lake ice melt water, we conclude that the amino acids detected in the meteorite are terrestrial contamination. We found that the exposure of a sample of Murchison to cold water lead to a substantial reduction over a period of several weeks in the amount of amino acids that are not strongly bound to the meteorite matrix. However, strongly bound amino acids that are extracted by direct HCl hydrolysis are not affected by the leaching process. Thus even if there had been leaching of amino acids from our Tagish Lake meteorite sample during its 3 month residence in Tagish Lake ice and melt water, a Murchison type abundance of endogenous amino acids in the meteorite would have still been readily detectable. The low amino acid content of Tagish Lake indicates that this meteorite originated fiom a different type of parent body than the CM and CI chondrites. The parent body was apparently devoid of the reagents such as aldehyldes/ketones, HCN and ammonia needed for the effective abiotic synthesis of amino acids. Based on reflectance spectral measurements, Tagish Lake has been associated with P- or D-type asteroids. If the Tagish Lake meteorite was indeed derived fiom these types of parent bodies, our understanding of these primitive asteroids needs to be reevaluated with respect to their potential inventory of biologically important organic compounds.

Amino acids in the Martian meteorite Nakhla

NASA Technical Reports Server (NTRS)

Glavin, D. P.; Bada, J. L.; Brinton, K. L.; McDonald, G. D.

1999-01-01

A suite of protein and nonprotein amino acids were detected with high-performance liquid chromatography in the water- and acid-soluble components of an interior fragment of the Martian meteorite Nakhla, which fell in Egypt in 1911. Aspartic and glutamic acids, glycine, alanine, beta-alanine, and gamma-amino-n-butyric acid (gamma-ABA) were the most abundant amino acids detected and were found primarily in the 6 M HCl-hydrolyzed, hot water extract. The concentrations ranged from 20 to 330 parts per billion of bulk meteorite. The amino acid distribution in Nakhla, including the D/L ratios (values range from <0.1 to 0.5), is similar to what is found in bacterially degraded organic matter. The amino acids in Nakhla appear to be derived from terrestrial organic matter that infiltrated the meteorite soon after its fall to Earth, although it is possible that some of the amino acids are endogenous to the meteorite. The rapid amino acid contamination of Martian meteorites after direct exposure to the terrestrial environment has important implications for Mars sample-return missions and the curation of the samples from the time of their delivery to Earth.

Amino acids in the Martian meteorite Nakhla.

PubMed

Glavin, D P; Bada, J L; Brinton, K L; McDonald, G D

1999-08-03

A suite of protein and nonprotein amino acids were detected with high-performance liquid chromatography in the water- and acid-soluble components of an interior fragment of the Martian meteorite Nakhla, which fell in Egypt in 1911. Aspartic and glutamic acids, glycine, alanine, beta-alanine, and gamma-amino-n-butyric acid (gamma-ABA) were the most abundant amino acids detected and were found primarily in the 6 M HCl-hydrolyzed, hot water extract. The concentrations ranged from 20 to 330 parts per billion of bulk meteorite. The amino acid distribution in Nakhla, including the D/L ratios (values range from <0.1 to 0.5), is similar to what is found in bacterially degraded organic matter. The amino acids in Nakhla appear to be derived from terrestrial organic matter that infiltrated the meteorite soon after its fall to Earth, although it is possible that some of the amino acids are endogenous to the meteorite. The rapid amino acid contamination of Martian meteorites after direct exposure to the terrestrial environment has important implications for Mars sample-return missions and the curation of the samples from the time of their delivery to Earth.

Amino acids in the Martian meteorite Nakhla

PubMed Central

Glavin, Daniel P.; Bada, Jeffrey L.; Brinton, Karen L. F.; McDonald, Gene D.

1999-01-01

A suite of protein and nonprotein amino acids were detected with high-performance liquid chromatography in the water- and acid-soluble components of an interior fragment of the Martian meteorite Nakhla, which fell in Egypt in 1911. Aspartic and glutamic acids, glycine, alanine, β-alanine, and γ-amino-n-butyric acid (γ-ABA) were the most abundant amino acids detected and were found primarily in the 6 M HCl-hydrolyzed, hot water extract. The concentrations ranged from 20 to 330 parts per billion of bulk meteorite. The amino acid distribution in Nakhla, including the d/l ratios (values range from <0.1 to 0.5), is similar to what is found in bacterially degraded organic matter. The amino acids in Nakhla appear to be derived from terrestrial organic matter that infiltrated the meteorite soon after its fall to Earth, although it is possible that some of the amino acids are endogenous to the meteorite. The rapid amino acid contamination of Martian meteorites after direct exposure to the terrestrial environment has important implications for Mars sample-return missions and the curation of the samples from the time of their delivery to Earth. PMID:10430856

Searching for Extraterrestrial Amino Acids in a Contaminated Meteorite: Amino Acid Analyses of the Canakkale L6 Chondrite

NASA Technical Reports Server (NTRS)

Burton, A. S.; Elsila, J. E.; Glavin, D. P.; Dworkin, J. P.; Ornek, C. Y.; Esenoglu, H. H.; Unsalan, O.; Ozturk, B.

2016-01-01

Amino acids can serve as important markers of cosmochemistry, as their abundances and isomeric and isotopic compositions have been found to vary predictably with changes in parent body chemistry and alteration processes. Amino acids are also of astrobiological interest because they are essential for life on Earth. Analyses of a range of meteorites, including all groups of carbonaceous chondrites, along with H, R, and LL chondrites, ureilites, and a martian shergottite, have revealed that amino acids of plausible extraterrestrial origin can be formed in and persist after a wide range of parent body conditions. However, amino acid analyses of L6 chondrites to date have not provided evidence for indigenous amino acids. In the present study, we performed amino acid analysis on larger samples of a different L6 chondite, Canakkale, to determine whether or not trace levels of indigenous amino acids could be found. The Canakkale meteor was an observed fall in late July, 1964, near Canakkale, Turkey. The meteorite samples (1.36 and 1.09 g) analyzed in this study were allocated by C. Y. Ornek, along with a soil sample (1.5 g) collected near the Canakkale recovery site.

Nonclinical Pharmacokinetics, Disposition, and Drug-Drug Interaction Potential of a Novel d-Amino Acid Peptide Agonist of the Calcium-Sensing Receptor AMG 416 (Etelcalcetide).

PubMed

Subramanian, Raju; Zhu, Xiaochun; Kerr, Savannah J; Esmay, Joel D; Louie, Steven W; Edson, Katheryne Z; Walter, Sarah; Fitzsimmons, Michael; Wagner, Mylo; Soto, Marcus; Pham, Roger; Wilson, Sarah F; Skiles, Gary L

2016-08-01

AMG 416 (etelcalcetide) is a novel synthetic peptide agonist of the calcium-sensing receptor composed of a linear chain of seven d-amino acids (referred to as the d-amino acid backbone) with a d-cysteine linked to an l-cysteine via a disulfide bond. AMG 416 contains four basic d-arginine residues and is a +4 charged peptide at physiologic pH with a mol. wt. of 1048.3 Da. The pharmacokinetics (PK), disposition, and potential of AMG 416 to cause drug-drug interaction were investigated in nonclinical studies with two single (14)C-labels placed either at a potentially metabolically labile acetyl position or on the d-alanine next to d-cysteine in the interior of the d-amino acid backbone. After i.v. dosing, the PK and disposition of AMG 416 were similar in male and female rats. Radioactivity rapidly distributed to most tissues in rats with intact kidneys, and renal elimination was the predominant clearance pathway. No strain-dependent differences were observed. In bilaterally nephrectomized rats, minimal radioactivity (1.2%) was excreted via nonrenal pathways. Biotransformation occurred primarily via disulfide exchange with endogenous thiol-containing molecules in whole blood rather than metabolism by enzymes, such as proteases or cytochrome P450s; the d-amino acid backbone remained unaltered. A substantial proportion of the plasma radioactivity was covalently conjugated to albumin. AMG 416 presents a low risk for P450 or transporter-mediated drug-drug interactions because it showed no interactions in vitro. These studies demonstrated a (14)C label on either the acetyl or the d-alanine in the d-amino acid backbone would be appropriate for clinical studies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Sites that Can Produce Left-handed Amino Acids in the Supernova Neutrino Amino Acid Processing Model

NASA Astrophysics Data System (ADS)

Boyd, Richard N.; Famiano, Michael A.; Onaka, Takashi; Kajino, Toshitaka

2018-03-01

The Supernova Neutrino Amino Acid Processing model, which uses electron anti-neutrinos and the magnetic field from a source object such as a supernova to selectively destroy one amino acid chirality, is studied for possible sites that would produce meteoroids with partially left-handed amino acids. Several sites appear to provide the requisite magnetic field intensities and electron anti-neutrino fluxes. These results have obvious implications for the origin of life on Earth.

Biopolymers Containing Unnatural Amino Acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, Peter

Although the main chain structure of polymers has a profound effect on their materials properties, the side groups can also have dramatic effects on their properties including conductivity, liquid crystallinity, hydrophobicity, elasticity and biodegradability. Unfortunately control over the side chain structure of polymers remains a challenge – it is difficult to control the sequence of chain elongation when mixtures of monomers are polymerized, and postpolymerization side chain modification is made difficult by polymer effects on side chain reactivity. In contrast, the mRNA templated synthesis of polypeptides on the ribosome affords absolute control over the primary sequence of the twenty aminomore » acid monomers. Moreover, the length of the biopolymer is precisely controlled as are sites of crosslinking. However, whereas synthetic polymers can be synthesized from monomers with a wide range of chemically defined structures, ribosomal biosynthesis is largely limited to the 20 canonical amino acids. For many applications in material sciences, additional building blocks would be desirable, for example, amino acids containing metallocene, photoactive, and halogenated side chains. To overcome this natural constraint we have developed a method that allows unnatural amino acids, beyond the common twenty, to be genetically encoded in response to nonsense or frameshift codons in bacteria, yeast and mammalian cells with high fidelity and good yields. Here we have developed methods that allow identical or distinct noncanonical amino acids to be incorporated at multiple sites in a polypeptide chain, potentially leading to a new class of templated biopolymers. We have also developed improved methods for genetically encoding unnatural amino acids. In addition, we have genetically encoded new amino acids with novel physical and chemical properties that allow selective modification of proteins with synthetic agents. Finally, we have evolved new metal-ion binding sites in

Genetics of Amino Acid Taste and Appetite.

PubMed

Bachmanov, Alexander A; Bosak, Natalia P; Glendinning, John I; Inoue, Masashi; Li, Xia; Manita, Satoshi; McCaughey, Stuart A; Murata, Yuko; Reed, Danielle R; Tordoff, Michael G; Beauchamp, Gary K

2016-07-01

The consumption of amino acids by animals is controlled by both oral and postoral mechanisms. We used a genetic approach to investigate these mechanisms. Our studies have shown that inbred mouse strains differ in voluntary amino acid consumption, and these differences depend on sensory and nutritive properties of amino acids. Like humans, mice perceive some amino acids as having a sweet (sucrose-like) taste and others as having an umami (glutamate-like) taste. Mouse strain differences in the consumption of some sweet-tasting amino acids (d-phenylalanine, d-tryptophan, and l-proline) are associated with polymorphisms of a taste receptor, type 1, member 3 gene (Tas1r3), and involve differential peripheral taste responsiveness. Strain differences in the consumption of some other sweet-tasting amino acids (glycine, l-alanine, l-glutamine, and l-threonine) do not depend on Tas1r3 polymorphisms and so must be due to allelic variation in other, as yet unknown, genes involved in sweet taste. Strain differences in the consumption of l-glutamate may depend on postingestive rather than taste mechanisms. Thus, genes and physiologic mechanisms responsible for strain differences in the consumption of each amino acid depend on the nature of its taste and postingestive properties. Overall, mouse strain differences in amino acid taste and appetite have a complex genetic architecture. In addition to the Tas1r3 gene, these differences depend on other genes likely involved in determining the taste and postingestive effects of amino acids. The identification of these genes may lead to the discovery of novel mechanisms that regulate amino acid taste and appetite. © 2016 American Society for Nutrition.

Protein and amino acid nutrition

USDA-ARS?s Scientific Manuscript database

Dairy cow protein and amino acid nutrition have a significant role in sustainable dairying. Protein, amino acids, and nitrogen are inextricably linked through effects in the rumen, metabolism of the cow, and environmental nutrient management. Feeding systems have been making progress toward emphasiz...

Amino Acid Contents of Meteorite Mineral Separates

NASA Technical Reports Server (NTRS)

Berger, E. L.; Burton, A. S; Locke, D.

2017-01-01

Indigenous amino acids have been found indigenous all 8 carbonaceous chondrite groups. However, the abundances, structural, enantiomeric and isotopic compositions of amino acids differ significantly among meteorites of different groups and petrologic types. This suggests that parent-body conditions (thermal or aqueous alteration), mineralogy, and the preservation of amino acids are linked. Previously, elucidating specific relationships between amino acids and mineralogy was not possible because the samples analyzed for amino acids were much larger than the scale at which petrologic heterogeneity is observed (sub mm-scale differences corresponding to sub-mg samples). Recent advances in amino acid measurements and application of techniques such as high resolution X-ray diffraction (HR-XRD) and scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) for mineralogical characterizations allow us to perform coordinated analyses on the scale at which mineral heterogeneity is observed.

Amino acids of the Murchison meteorite. II - Five carbon acyclic primary beta-, gamma-, and delta-amino alkanoic acids

NASA Technical Reports Server (NTRS)

Cronin, J. R.; Pizzarello, S.; Yuen, G. U.

1985-01-01

The five-carbon acyclic primary beta, gamma, and delta amino alkanoic acids of the Murchison meteorite are studied using gas chromatography-mass spectrometry and ion exchange chromatography. The chromatograms reveal that alpha is the most abundant monoamino alkanoic acid followed by gamma and beta, and an exponential increase in the amount of amino acid is observed as the carbon number increases in the homologous series. The influence of frictional heating, spontaneous thermal decomposition, and radiation of the synthesis of amino acids is examined. The data obtained support an amino acid synthesis process involving random combination of single-carbon precursors.

gamma-Glutamyl amino acids. Transport and conversion to 5-oxoproline in the kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bridges, R.J.; Meister, A.

1985-06-25

Transport of gamma-glutamyl amino acids, a step in the proposed glutathione-gamma-glutamyl transpeptidase-mediated amino acid transport pathway, was examined in mouse kidney. The transport of gamma-glutamyl amino acids was demonstrated in vitro in studies on kidney slices. Transport was followed by measuring uptake of /sup 35/S after incubation of the slices in media containing gamma-glutamyl methionine (/sup 35/S)sulfone. The experimental complication associated with extracellular conversion of the gamma-glutamyl amino acid to amino acid and uptake of the latter by slices was overcome by using 5-oxoproline formation (catalyzed by intracellular gamma-glutamyl-cyclotransferase) as an indicator of gamma-glutamyl amino acid transport. This method wasmore » also successfully applied to studies on transport of gamma-glutamyl amino acids in vivo. Transport of gamma-glutamyl amino acids in vitro and in vivo is inhibited by several inhibitors of gamma-glutamyl transpeptidase and also by high extracellular levels of glutathione. This seems to explain urinary excretion of gamma-glutamylcystine by humans with gamma-glutamyl transpeptidase deficiency and by mice treated with inhibitors of this enzyme. Mice depleted of glutathione by treatment with buthionine sulfoximine (which inhibits glutathione synthesis) or by treatment with 2,6-dimethyl-2,5-heptadiene-4-one (which effectively interacts with tissue glutathione) exhibited significantly less transport of gamma-glutamyl amino acids than did untreated controls. The findings suggest that intracellular glutathione functions in transport of gamma-glutamyl amino acids. Evidence was also obtained for transport of gamma-glutamyl gamma-glutamylphenylalanine into kidney slices.« less

Pharmacokinetics of amino acid ester prodrugs of Acyclovir after oral administration: Interaction with the transporters on Caco-2 cells

PubMed Central

Katragadda, Suresh; Jain, Ritesh; Kwatra, Deep; Hariharan, Sudharshan; Mitra, Ashim K.

2008-01-01

In vivo systemic absorption of the amino acid prodrugs of acyclovir (ACV) after oral administration was evaluated in rats. Stability of the prodrugs, L-Alanine-ACV (AACV), L-Serine-ACV (SACV), L-Isoleucine-ACV (IACV), γ-Glutamate-ACV (EACV) and L-Valine-ACV (VACV) was evaluated in various tissues. Interaction of these prodrugs with the transporters on Caco-2 cells was studied. In vivo systemic bioavailability of these prodrugs upon oral administration was evaluated in jugular vein cannulated rats. The amino acid ester prodrugs showed affinity towards various amino acid transporters as well as the peptide transporter on the Caco-2 cells. In terms of stability, EACV was most enzymatically stable compared to other prodrugs especially in liver homogenate. In oral absorption studies, ACV and AACV showed high terminal elimination rate constants (λz). SACV and VACV exhibited approximately five fold increase in area under the curve (AUC) values relative to ACV (p<0.05). Cmax(T) (maximum concentration) of SACV was observed to be 39 ± 22 µM in plasma which is 2 times better than VACV and 15 times better than ACV. Clast(T) (concentration at the last time point) of SACV was observed to be 0.18 ± 0.06 µM in plasma which is 2 times better than VACV and 3 times better than ACV. Amino acid ester prodrugs of ACV were absorbed at varying amounts (Cmax) and eliminated at varying rates (λz) thereby leading to varying extents (AUC). The amino acid ester prodrug SACV owing to its enhanced stability, higher AUC and better concentration at last time point seems to be a promising candidate for the oral treatment of herpes infections. PMID:18638532

Discovery and History of Amino Acid Fermentation.

PubMed

Hashimoto, Shin-Ichi

There has been a strong demand in Japan and East Asia for L-glutamic acid as a seasoning since monosodium glutamate was found to present umami taste in 1907. The discovery of glutamate fermentation by Corynebacterium glutamicum in 1956 enabled abundant and low-cost production of the amino acid, creating a large market. The discovery also prompted researchers to develop fermentative production processes for other L-amino acids, such as lysine. Currently, the amino acid fermentation industry is so huge that more than 5 million metric tons of amino acids are manufactured annually all over the world, and this number continues to grow. Research on amino acid fermentation fostered the notion and skills of metabolic engineering which has been applied for the production of other compounds from renewable resources. The discovery of glutamate fermentation has had revolutionary impacts on both the industry and science. In this chapter, the history and development of glutamate fermentation, including the very early stage of fermentation of other amino acids, are reviewed.

Research for amino acids in lunar samples.

NASA Technical Reports Server (NTRS)

Gehrke, C. W.; Zumwalt, R. W.; Kuo, K.; Rash, J. J.; Aue , W. A.; Stalling, D. L.; Kvenvolden, K. A.; Ponnamperuma, C.

1972-01-01

The study was primarily directed toward the examination of Apollo 14 lunar fines for indigenous amino acids or materials which could be converted to amino acids on hydrolysis with 6 N hydrochloric acid. Initial experiments were conducted to confirm the integrity of the derivatization reactions and reagents, and to optimize the gas-liquid chromatographic (GLC) instrumental and chromatographic system for the separation and flame ionization detection of the amino acid derivatives. In studies on the recovery of amino acids added to lunar fines, low recoveries were obtained when 10 ng of each amino acid were added to 50 mg of virgin fines, but the subsequent addition of 50 ng of each to the previously extracted sample resulted in much higher recoveries.

Extraterrestrial Amino Acids in the Almahata Sitta Meteorite

NASA Technical Reports Server (NTRS)

Glavin, Daniel P.; Aubrey, Andrew D.; Callahan, Michael P.; Dworkin, Jason P.; Elsila, Jamie E.; Parker, Eric T.; Bada, Jeffrey L.

2009-01-01

Amino acid analysis of a meteorite fragment of asteroid 2008 TC(sub 3) called Almahata Sitta was carried out using reverse-phase high-perfo rmance liquid chromatography coupled with UV fluorescence detection a nd time-of-flight mass spectrometry (HPLC-FD/ToF-MS) as part of a sam ple analysis consortium. HPLC analyses of hot-water extracts from the meteorite revealed a complex distribution of two- to six-carbon aliph atic amino acids and one- to three carbon amines with abundances rang ing from 0.5 to 149 parts-per-billion (ppb). The enantiomeric ratios of the amino acids alanine, Beta-amino-n-butyric acid (Beta-ABA), 2-amino-2- methylbutanoic acid (isovaline), and 2-aminopentanoic acid (no rvaline) in the meteorite were racemic (D/L approximately 1), indicat ing that these amino acids are indigenous to the meteorite and not te rrestrial contaminants. Several other non-protein amino acids were also identified in the meteorite above background levels including alpha -aminoisobutyric acid (alpha-AIB), 4-amino-2- methybutanoic acid, 4-a mino-3-methylbutanoic acid, and 3-, 4-, and 5-aminopentanoic acid. Th e total abundances of isovaline and AlB in Almahata Sitta are approximately 1000 times lower than the abundances of these amino acids found in the CM carbonaceous meteorite Murchison. The extremely love abund ances and unusual distribution of five carbon amino acids in Almahata Sitta compared to Cl, CM, and CR carbonaceous meteorites and may be due to extensive thermal alteration of amino acids on the parent aster oid by partial melting during formation or impact shock heating.

Amino acids in the Yamato carbonaceous chrondrite from Antarctica

NASA Technical Reports Server (NTRS)

Shimoyama, A.; Ponnamperuma, C.; Yanai, K.

1979-01-01

Evidence for the presence of amino acids of extraterrestrial origin in the Antarctic Yamato carbonaceous chrondrite is presented. Hydrolyzed and nonhydrolyzed water-extracted amino acid samples from exterior, middle and interior portions of the meteorite were analyzed by an amino acid analyzer and by gas chromatography of N-TFA-isopropyl amino acid derivatives. Nine protein and six nonprotein amino acids were detected in the meteorite at abundances between 34 and less than one nmole/g, with equal amounts in interior and exterior portions. Nearly equal abundances of the D and L enantiomers of alanine, aspartic acid and glutamic acid were found, indicating the abiotic, therefore extraterrestrial, origin of the amino acids. The Antarctic environment and the uniformity of protein amino acid abundances are discussed as evidence against the racemization of terrestrially acquired amino acids, and similarities between Yamato amino acid compositions and the amino acid compositions of the Murchison and Murray type II carbonaceous chrondrites are indicated.

Drug-nutrient interactions: inhibition of amino acid intestinal absorption by fluoxetine.

PubMed

Urdaneta, E; Idoate, I; Larralde, J

1998-05-01

Fluoxetine is one of the most widely used antidepressants and nowadays it is also being used to manage obesity problems. In our laboratory we demonstrated that the drug inhibited sugar absorption (Monteiro et al. 1993). The aim of the present work was to determine the effect of fluoxetine on intestinal leucine absorption. Using a procedure of successive absorptions in vivo the drug diminished amino acid absorption by 30% (P < 0.001). Experiments in vitro in isolated jejunum also revealed a reduction in leucine uptake of 37% (P < 0.001). In both cases fluoxetine only affected mediated transport without altering diffusion. In a preparation enriched in basolateral membrane, fluoxetine inhibited the Na+,K(+)-ATPase (EC 3.6.1.37) activity (55%; P < 0.001) in a non-competitive manner with an inhibition constant (Ki) value of 0.92 mM. Leucine uptake by brush-border membrane vesicles was diminished by the drug (a reduction of 48% was observed at 30s, P < 0.001); only the apical Na(+)-dependent transport system of the amino acid was modified and the inhibition was non-competitive. Leucine uptake in the presence of lysine indicated that transporter B was involved. These results suggest that fluoxetine reduces leucine absorption by its action on the basolateral and apical membrane of the enterocyte; the nutritional status of the patients under drug treatment may be affected as neutral amino acid absorption is decreased.

Interactions among the branched-chain amino acids and their effects on methionine utilization in growing pigs: effects on plasma amino- and keto-acid concentrations and branched-chain keto-acid dehydrogenase activity.

PubMed

Langer, S; Scislowski, P W; Brown, D S; Dewey, P; Fuller, M F

2000-01-01

The present experiment was designed to elucidate the mechanism of the methionine-sparing effect of excess branched-chain amino acids (BCAA) reported in the previous paper (Langer & Fuller, 2000). Twelve growing gilts (30-35 kg) were prepared with arterial catheters. After recovery, they received for 7 d a semipurified diet with a balanced amino acid pattern. On the 7th day blood samples were taken before (16 h postabsorptive) and after the morning meal (4 h postprandial). The animals were then divided into three groups and received for a further 7 d a methionine-limiting diet (80% of requirement) (1) without any amino acid excess; (2) with excess leucine (50% over requirement); or (3) with excesses of all three BCAA (leucine, isoleucine, valine, each 50% over the requirement). On the 7th day blood samples were taken as in the first period, after which the animals were killed and liver and muscle samples taken. Plasma amino acid and branched-chain keto acid (BCKA) concentrations in the blood and branched-chain keto-acid dehydrogenase (BCKDH; EC 1.2.4.4) activity in liver and muscle homogenates were determined. Compared with those on the balanced diet, pigs fed on methionine-limiting diets had significantly lower (P < 0.05) plasma methionine concentrations in the postprandial but not in the postabsorptive state. There was no effect of either leucine or a mixture of all three BCAA fed in excess on plasma methionine concentrations. Excess dietary leucine reduced (P < 0.05) the plasma concentrations of isoleucine and valine in both the postprandial and postabsorptive states. Plasma concentrations of the BCKA reflected the changes in the corresponding amino acids. Basal BCKDH activity in the liver and total BCKDH activity in the biceps femoris muscle were significantly (P < 0.05) increased by excesses of leucine or all BCAA.

Using porphyrin-amino acid pairs to model the electrochemistry of heme proteins: experimental and theoretical investigations.

PubMed

Samajdar, Rudra N; Manogaran, Dhivya; Yashonath, S; Bhattacharyya, Aninda J

2018-04-18

Quasi reversibility in electrochemical cycling between different oxidation states of iron is an often seen characteristic of iron containing heme proteins that bind dioxygen. Surprisingly, the system becomes fully reversible in the bare iron-porphyrin complex: hemin. This leads to the speculation that the polypeptide bulk (globin) around the iron-porphyrin active site in these heme proteins is probably responsible for the electrochemical quasi reversibility. To understand the effect of such polypeptide bulk on iron-porphyrin, we study the interaction of specific amino acids with the hemin center in solution. We choose three representative amino acids-histidine (a well-known iron coordinator in bio-inorganic systems), tryptophan (a well-known fluoroprobe for proteins), and cysteine (a redox-active organic molecule). The interactions of these amino acids with hemin are studied using electrochemistry, spectroscopy, and density functional theory. The results indicate that among these three, the interaction of histidine with the iron center is strongest. Further, histidine maintains the electrochemical reversibility of iron. On the other hand, tryptophan and cysteine interact weakly with the iron center but disturb the electrochemical reversibility by contributing their own redox active processes to the system. Put together, this study attempts to understand the molecular interactions that can control electrochemical reversibility in heme proteins. The results obtained here from the three representative amino acids can be scaled up to build a heme-amino acid interaction database that may predict the electrochemical properties of any protein with a defined polypeptide sequence.

The oxidation of amino acids by ferrate(V). A pre-mix pulse radiolysis study.

PubMed

Rush, J D; Bielski, B H

1995-06-01

The forms of ferrate(V) which are derived from the one-electron reduction of potassium ferrate (K2FeO4) by ethanol radicals react with representative amino acids (glycine, methionine, phenylalanine and serine) at rates that are greater than 10(5)M-1s-1 near pH 10. The predominant interaction in the alkaline pH range is between the protonated ferrate(V) species, HFeO4(2-), and the amino acid anion. Fe(V) + amino acid-->Fe(III) + NH3 + alpha-keto acid The rate-determining process is the two electron reduction of ferrate(V) to iron(III) with oxidation and subsequent deamination of the amino acid. The reaction appears to involve an entry of the amino acid into the inner coordination sphere of ferrate(V). In all cases, ferrate(V) exhibits preferred attack on the amino group in contrast to the OH radical which attacks the thioether site of methionine and the phenyl ring of phenylalanine.

Extraterrestrial material analysis: loss of amino acids during liquid-phase acid hydrolysis

NASA Astrophysics Data System (ADS)

Buch, Arnaud; Brault, Amaury; Szopa, Cyril; Freissinet, Caroline

2015-04-01

Searching for building blocks of life in extraterrestrial material is a way to learn more about how life could have appeared on Earth. With this aim, liquid-phase acid hydrolysis has been used, since at least 1970 , in order to extract amino acids and other organic molecules from extraterrestrial materials (e.g. meteorites, lunar fines) or Earth analogues (e.g. Atacama desert soil). This procedure involves drastic conditions such as heating samples in 6N HCl for 24 h, either under inert atmosphere/vacuum, or air. Analysis of the hydrolyzed part of the sample should give its total (free plus bound) amino acid content. The present work deals with the influence of the 6N HCl hydrolysis on amino acid degradation. Our experiments have been performed on a standard solution of 17 amino acids. After liquid-phase acid hydrolysis (6N HCl) under argon atmosphere (24 h at 100°C), the liquid phase was evaporated and the dry residue was derivatized with N-Methyl-N-(t-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) and dimethylformamide (DMF), followed by gas chromatography-mass spectrometry analysis. After comparison with derivatized amino acids from the standard solution, a significant reduction of the chromatographic peak areas was observed for most of the amino acids after liquid-phase acid hydrolysis. Furthermore, the same loss pattern was observed when the amino acids were exposed to cold 6N HCl for a short amount of time. The least affected amino acid, i.e. glycine, was found to be 73,93% percent less abundant compared to the non-hydrolyzed standard, while the most affected, i.e. histidine, was not found in the chromatograms after hydrolysis. Our experiments thereby indicate that liquid-phase acid hydrolysis, even under inert atmosphere, leads to a partial or total loss of all of the 17 amino acids present in the standard solution, and that a quick cold contact with 6N HCl is sufficient to lead to a loss of amino acids. Therefore, in the literature, the reported increase

Distribution of Amino Acids in Lunar Regolith

NASA Technical Reports Server (NTRS)

Elsila, J. E.; Callahan, M. P.; Glavin, D. P.; Dworkin, J. P.; Noble, S. K.; Gibson, E. K., Jr.

2014-01-01

One of the most eagerly studied questions upon initial return of lunar samples was whether significant amounts of organic compounds, including amino acids, were present. Analyses during the 1970s produced only tentative and inconclusive identifications of indigenous amino acids. Those analyses were hampered by analytical difficulties including relative insensitivity to certain compounds, the inability to separate chiral enantiomers, and the lack of compound-specific isotopic measurements, which made it impossible to determine whether the detected amino acids were indigenous to the lunar samples or the results of contamination. Numerous advances have been made in instrumentation and methodology for amino acid characterization in extraterrestrial samples in the intervening years, yet the origin of amino acids in lunar regolith samples has been revisited only once for a single lunar sample, (3) and remains unclear. Here, we present initial data from the analyses of amino acid abundances in 12 lunar regolith samples. We discuss these abundances in the context of four potential amino acid sources: (1) terrestrial biological contamination; (2) contamination from lunar module (LM) exhaust; (3) derivation from solar windimplanted precursors; and (4) exogenous delivery from meteorites.

Influence of biopolymers on the solubility of branched-chain amino acids and stability of their solutions.

PubMed

Hong, Chi Rac; Lee, Gyu Whan; Paik, Hyun-Dong; Chang, Pahn-Shick; Choi, Seung Jun

2018-01-15

This study confirmed the possibility of biopolymer-type stabilizers to increase the saturation concentration of branched-chain amino acids by preventing their crystallization/precipitation. Although microfluidization increased the initial solubility, it failed to increase the saturation concentration of the branched-chain amino acids. The saturation concentration of the branched-chain amino acids increased from 3.81% to 4.42% and 4.85% after the incorporation of food hydrocolloids and proteins, respectively. However, the branched-chain amino acids:stabilizer ratio did not affect the solubility. In the case of food hydrocolloid-based solutions, crystal formation and growth of branched-chain amino acids occurred during storage, resulting in the precipitation of branched-chain amino acid crystals. However, food proteins effectively increased the stability of the solubilized branched-chain amino acids. The improved solubility and stability of the solubilized branched-chain amino acids could be attributed to interactions between the functional groups (carboxyl, amine, sulfate, aliphatic, aromatic, etc.) of the stabilizer and the branched-chain amino acid molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

Theoretical study of interactions between cysteine and perfluoropropanoic acid in gas and aqueous phase

NASA Astrophysics Data System (ADS)

Holmes, Tiffani M.; Doskocz, Jacek; Wright, Terrance; Hill, Glake A.

The interaction of perfluoropropanoic acid (PFPA) with the amino acid cysteine was investigated using density functional theory. Previous studies suggest that the peroxisome proliferator chemical, perfluorooctanoic acid, is circulated throughout the body by way of sulfur-containing amino acids. We present conformational analysis of the interactions of PFPA, a small model of perfluorooctanoic acid, with the sulfur-containing amino acid which occur by the process of hydrogen bonding, in which the hydrogen of the sulfhydryl group interacts with the carboxyl oxygen, and the amino nitrogen forms a hydrogen bond with the hydrogen of the bond OH group of the fluorinated alkyl. We also show in our structures a recently characterized weak nonbonded interaction between divalent sulfur and a main chain carboxyl oxygen in proteins. B3LYP calculated free energies and interaction energies predict low-energy, high-interaction conformations for complex systems of perfluorinated fatty acid interactions with cysteine.

Hormone regulation of rhizome development in tall fescue (Festuca arundinacea) associated with proteomic changes controlling respiratory and amino acid metabolism.

PubMed

Ma, Xiqing; Xu, Qian; Meyer, William A; Huang, Bingru

2016-09-01

Rhizomes are underground stems with meristematic tissues capable of generating shoots and roots. However, mechanisms controlling rhizome formation and growth are yet to be completely understood. The objectives of this study were to investigate whether rhizome development could be regulated by cytokinins (CKs) and gibberellic acids (GAs), and determine underlying mechanisms of regulation of rhizome formation and growth of tall fescue (Festuca arundinacea) by a CK or GA through proteomic and transcript analysis. A rhizomatous genotype of tall fescue ('BR') plants were treated with 6-benzylaminopurine (BAP, a synthetic cytokinin) or GA3 in hydroponic culture in growth chambers. Furthermore, comparative proteomic analysis of two-dimensional electrophoresis and mass spectrometry were performed to investigate proteins and associated metabolic pathways imparting increased rhizome number by BAP and rhizome elongation by GA3 KEY RESULTS: BAP stimulated rhizome formation while GA3 promoted rhizome elongation. Proteomic analysis identified 76 differentially expressed proteins (DEPs) due to BAP treatment and 37 DEPs due to GA3 treatment. Cytokinin-related genes and cell division-related genes were upregulated in the rhizome node by BAP and gibberellin-related and cell growth-related genes in the rhizome by GA3 CONCLUSIONS: Most of the BAP- or GA-responsive DEPs were involved in respiratory metabolism and amino acid metabolism. Transcription analysis demonstrated that genes involved in hormone metabolism, signalling pathways, cell division and cell-wall loosening were upregulated by BAP or GA3 The CK and GA promoted rhizome formation and growth, respectively, by activating metabolic pathways that supply energy and amino acids to support cell division and expansion during rhizome initiation and elongation in tall fescue. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Amino acids as antioxidants for frying oil

USDA-ARS?s Scientific Manuscript database

Amino acids, proteins and hydrolysates of proteins have been known to protect edible oils from oxidation. While amino acids and related materials have high potential as antioxidants for frying oil, effectiveness of each amino acid and mechanisms of their activities are not well understood yet. Propo...

Identification of Amino Acids in the Human Tetherin Transmembrane Domain Responsible for HIV-1 Vpu Interaction and Susceptibility▿ †

PubMed Central

Kobayashi, Tomoko; Ode, Hirotaka; Yoshida, Takeshi; Sato, Kei; Gee, Peter; Yamamoto, Seiji P.; Ebina, Hirotaka; Strebel, Klaus; Sato, Hironori; Koyanagi, Yoshio

2011-01-01

Tetherin, also known as BST-2/CD317/HM1.24, is an antiviral cellular protein that inhibits the release of HIV-1 particles from infected cells. HIV-1 viral protein U (Vpu) is a specific antagonist of human tetherin that might contribute to the high virulence of HIV-1. In this study, we show that three amino acid residues (I34, L37, and L41) in the transmembrane (TM) domain of human tetherin are critical for the interaction with Vpu by using a live cell-based assay. We also found that the conservation of an additional amino acid at position 45 and two residues downstream of position 22, which are absent from monkey tetherins, are required for the antagonism by Vpu. Moreover, computer-assisted structural modeling and mutagenesis studies suggest that an alignment of these four amino acid residues (I34, L37, L41, and T45) on the same helical face in the TM domain is crucial for the Vpu-mediated antagonism of human tetherin. These results contribute to the molecular understanding of human tetherin-specific antagonism by HIV-1 Vpu. PMID:21068238

Plasma free amino acid kinetics in rainbow trout (Oncorhynchus mykiss) using a bolus injection of 15N-labeled amino acids.

PubMed

Robinson, Jacob William; Yanke, Dan; Mirza, Jeff; Ballantyne, James Stuart

2011-02-01

To gain insight into the metabolic design of the amino acid carrier systems in fish, we injected a bolus of (15)N amino acids into the dorsal aorta in mature rainbow trout (Oncorhynchus mykiss). The plasma kinetic parameters including concentration, pool size, rate of disappearance (R(d)), half-life and turnover rate were determined for 15 amino acids. When corrected for metabolic rate, the R(d) values obtained for trout for most amino acids were largely comparable to human values, with the exception of glutamine (which was lower) and threonine (which was higher). R(d) values ranged from 0.9 μmol 100 g(-1) h(-1) (lysine) to 22.1 μmol 100 g(-1) h(-1) (threonine) with most values falling between 2 and 6 μmol 100 g(-1) h(-1). There was a significant correlation between R(d) and the molar proportion of amino acids in rainbow trout whole body protein hydrolysate. Other kinetic parameters did not correlate significantly with whole body amino acid composition. This indicates that an important design feature of the plasma-free amino acids system involves proportional delivery of amino acids to tissues for protein synthesis.

Gemini surfactants from natural amino acids.

PubMed

Pérez, Lourdes; Pinazo, Aurora; Pons, Ramon; Infante, Mrosa

2014-03-01

In this review, we report the most important contributions in the structure, synthesis, physicochemical (surface adsorption, aggregation and phase behaviour) and biological properties (toxicity, antimicrobial activity and biodegradation) of Gemini natural amino acid-based surfactants, and some potential applications, with an emphasis on the use of these surfactants as non-viral delivery system agents. Gemini surfactants derived from basic (Arg, Lys), neutral (Ser, Ala, Sar), acid (Asp) and sulphur containing amino acids (Cys) as polar head groups, and Geminis with amino acids/peptides in the spacer chain are reviewed. © 2013.

Modular Organization of Residue-Level Contacts Shapes the Selection Pressure on Individual Amino Acid Sites of Ribosomal Proteins.

PubMed

Mallik, Saurav; Kundu, Sudip

2017-04-01

Understanding the molecular evolution of macromolecular complexes in the light of their structure, assembly, and stability is of central importance. Here, we address how the modular organization of native molecular contacts shapes the selection pressure on individual residue sites of ribosomal complexes. The bacterial ribosomal complex is represented as a residue contact network where nodes represent amino acid/nucleotide residues and edges represent their van der Waals interactions. We find statistically overrepresented native amino acid-nucleotide contacts (OaantC, one amino acid contacts one or multiple nucleotides, internucleotide contacts are disregarded). Contact number is defined as the number of nucleotides contacted. Involvement of individual amino acids in OaantCs with smaller contact numbers is more random, whereas only a few amino acids significantly contribute to OaantCs with higher contact numbers. An investigation of structure, stability, and assembly of bacterial ribosome depicts the involvement of these OaantCs in diverse biophysical interactions stabilizing the complex, including high-affinity protein-RNA contacts, interprotein cooperativity, intersubunit bridge, packing of multiple ribosomal RNA domains, etc. Amino acid-nucleotide constituents of OaantCs with higher contact numbers are generally associated with significantly slower substitution rates compared with that of OaantCs with smaller contact numbers. This evolutionary rate heterogeneity emerges from the strong purifying selection pressure that conserves the respective amino acid physicochemical properties relevant to the stabilizing interaction with OaantC nucleotides. An analysis of relative molecular orientations of OaantC residues and their interaction energetics provides the biophysical ground of purifying selection conserving OaantC amino acid physicochemical properties. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and

Distinctive Roles of D-Amino Acids in the Homochiral World: Chirality of Amino Acids Modulates Mammalian Physiology and Pathology.

PubMed

Sasabe, Jumpei; Suzuki, Masataka

2018-05-22

Living organisms enantioselectively employ L-amino acids as the molecular architecture of protein synthesized in the ribosome. Although L-amino acids are dominantly utilized in most biological processes, accumulating evidence points to the distinctive roles of D-amino acids in non-ribosomal physiology. Among the three domains of life, bacteria have the greatest capacity to produce a wide variety of D-amino acids. In contrast, archaea and eukaryotes are thought generally to synthesize only two kinds of D-amino acids: D-serine and D-aspartate. In mammals, D-serine is critical for neurotransmission as an endogenous coagonist of N-methyl D-aspartate receptors. Additionally, D-aspartate is associated with neurogenesis and endocrine systems. Furthermore, recognition of D-amino acids originating in bacteria is linked to systemic and mucosal innate immunity. Among the roles played by D-amino acids in human pathology, the dysfunction of neurotransmission mediated by D-serine is implicated in psychiatric and neurological disorders. Non-enzymatic conversion of L-aspartate or L-serine residues to their D-configurations is involved in age-associated protein degeneration. Moreover, the measurement of plasma or urinary D-/L-serine or D-/L-aspartate levels may have diagnostic or prognostic value in the treatment of kidney diseases. This review aims to summarize current understanding of D-amino-acid-associated biology with a major focus on mammalian physiology and pathology.

Adsorption and release of amino acids mixture onto apatitic calcium phosphates analogous to bone mineral

NASA Astrophysics Data System (ADS)

El Rhilassi, A.; Mourabet, M.; El Boujaady, H.; Bennani-Ziatni, M.; Hamri, R. El; Taitai, A.

2012-10-01

Study focused on the interaction of adsorbate with poorly crystalline apatitic calcium phosphates analogous to bone mineral. Calcium phosphates prepared in water-ethanol medium at physiological temperature (37 °C) and neutral pH, their Ca/P ratio was between 1.33 and 1.67. Adsorbate used in this paper takes the mixture form of two essential amino acids L-lysine and DL-leucine which have respectively a character hydrophilic and hydrophobic. Adsorption and release are investigated experimentally; they are dependent on the phosphate type and on the nature of adsorbate L-lysine, DL-leucine and their mixture. Adsorption of mixture of amino acids on the apatitic calcium phosphates is influenced by the competition between the two amino acids: L-lysine and DL-leucine which exist in the medium reaction. The adsorption kinetics is very fast while the release kinetics is slow. The chemical composition of apatite has an influence on both adsorption and release. The interactions adsorbate-adsorbent are electrostatic type. Adsorption and release reactions of the amino acid mixture are explained by the existence of the hydrated surface layer of calcium phosphate apatite. The charged sbnd COOsbnd and sbnd NH3+ of adsorbates are the strongest groups that interact with the surface of apatites, the adsorption is mainly due to the electrostatic interaction between the groups sbnd COOsbnd of amino acids and calcium Ca2+ ions of the apatite. Comparative study of interactions between adsorbates (L-lysine, DL-leucine and their mixture) and apatitic calcium phosphates is carried out in vitro by using UV-vis and infrared spectroscopy IR techniques.

Amino Acids Regulate Transgene Expression in MDCK Cells

PubMed Central

Torrente, Marta; Guetg, Adriano; Sass, Jörn Oliver; Arps, Lisa; Ruckstuhl, Lisa; Camargo, Simone M. R.; Verrey, François

2014-01-01

Gene expression and cell growth rely on the intracellular concentration of amino acids, which in metazoans depends on extracellular amino acid availability and transmembrane transport. To investigate the impact of extracellular amino acid concentrations on the expression of a concentrative amino acid transporter, we overexpressed the main kidney proximal tubule luminal neutral amino acid transporter B0AT1-collectrin (SLC6A19-TMEM27) in MDCK cell epithelia. Exogenously expressed proteins co-localized at the luminal membrane and mediated neutral amino acid uptake. However, the transgenes were lost over few cell culture passages. In contrast, the expression of a control transgene remained stable. To test whether this loss was due to inappropriately high amino acid uptake, freshly transduced MDCK cell lines were cultivated either with physiological amounts of amino acids or with the high concentration found in standard cell culture media. Expression of exogenous transporters was unaffected by physiological amino acid concentration in the media. Interestingly, mycoplasma infection resulted in a significant increase in transgene expression and correlated with the rapid metabolism of L-arginine. However, L-arginine metabolites were shown to play no role in transgene expression. In contrast, activation of the GCN2 pathway revealed by an increase in eIF2α phosphorylation may trigger transgene derepression. Taken together, high extracellular amino acid concentration provided by cell culture media appears to inhibit the constitutive expression of concentrative amino acid transporters whereas L-arginine depletion by mycoplasma induces the expression of transgenes possibly via stimulation of the GCN2 pathway. PMID:24797296

A Complex Prime Numerical Representation of Amino Acids for Protein Function Comparison.

PubMed

Chen, Duo; Wang, Jiasong; Yan, Ming; Bao, Forrest Sheng

2016-08-01

Computationally assessing the functional similarity between proteins is an important task of bioinformatics research. It can help molecular biologists transfer knowledge on certain proteins to others and hence reduce the amount of tedious and costly benchwork. Representation of amino acids, the building blocks of proteins, plays an important role in achieving this goal. Compared with symbolic representation, representing amino acids numerically can expand our ability to analyze proteins, including comparing the functional similarity of them. Among the state-of-the-art methods, electro-ion interaction pseudopotential (EIIP) is widely adopted for the numerical representation of amino acids. However, it could suffer from degeneracy that two different amino acid sequences have the same numerical representation, due to the design of EIIP. In light of this challenge, we propose a complex prime numerical representation (CPNR) of amino acids, inspired by the similarity between a pattern among prime numbers and the number of codons of amino acids. To empirically assess the effectiveness of the proposed method, we compare CPNR against EIIP. Experimental results demonstrate that the proposed method CPNR always achieves better performance than EIIP. We also develop a framework to combine the advantages of CPNR and EIIP, which enables us to improve the performance and study the unique characteristics of different representations.

Amino acid homeostasis and signalling in mammalian cells and organisms

PubMed Central

Bröer, Angelika

2017-01-01

Cells have a constant turnover of proteins that recycle most amino acids over time. Net loss is mainly due to amino acid oxidation. Homeostasis is achieved through exchange of essential amino acids with non-essential amino acids and the transfer of amino groups from oxidised amino acids to amino acid biosynthesis. This homeostatic condition is maintained through an active mTORC1 complex. Under amino acid depletion, mTORC1 is inactivated. This increases the breakdown of cellular proteins through autophagy and reduces protein biosynthesis. The general control non-derepressable 2/ATF4 pathway may be activated in addition, resulting in transcription of genes involved in amino acid transport and biosynthesis of non-essential amino acids. Metabolism is autoregulated to minimise oxidation of amino acids. Systemic amino acid levels are also tightly regulated. Food intake briefly increases plasma amino acid levels, which stimulates insulin release and mTOR-dependent protein synthesis in muscle. Excess amino acids are oxidised, resulting in increased urea production. Short-term fasting does not result in depletion of plasma amino acids due to reduced protein synthesis and the onset of autophagy. Owing to the fact that half of all amino acids are essential, reduction in protein synthesis and amino acid oxidation are the only two measures to reduce amino acid demand. Long-term malnutrition causes depletion of plasma amino acids. The CNS appears to generate a protein-specific response upon amino acid depletion, resulting in avoidance of an inadequate diet. High protein levels, in contrast, contribute together with other nutrients to a reduction in food intake. PMID:28546457

Concentration variations of amino acids in mammalian fossils: effects of diagenesis and the implications for amino acid racemization analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blackwell, B.; Rutter, N.W.

Detailed amino acid analysis of bones, teeth, and antler from several mammal species have shown that concentrations of several amino acids can be related to three factors: type of material analyzed, diagenetic alteration of the material, and relative age of the fossil. Concentrations of several amino acids are significantly different in enamel compared to those of dentine or cement. This can be used to check that no contamination of one material by another has occurred, which is critical for using the data for amino acid dating, since all three materials have different racemization rates for some acids. With increased inmore » growth of secondary minerals, generally reduced amino acid concentrations are observed. Interacid ratios and concentrations vary significantly the norms expected for the type of material with increasing degrees of alteration. These effects can be linked to abnormal racemization ratios observed in the same samples. Therefore, abnormal concentrations and/or interacid ratios can be used to detect samples in which the D/L amino acid ratios otherwise appear normal, thereby insuring better accuracy of amino acid racemization analysis. For unaltered fossils, with increasing sample age regardless the type of material, some amino acids steadily degrade, while others actually increase in concentration initially due to their generation as by-products of decay. Preliminary studies indicate that this progressive alteration can used to complement racemization data for determining relative stratigraphic sequences.« less

Amino Acid Sensing in Skeletal Muscle

PubMed Central

Moro, Tatiana; Ebert, Scott M.; Adams, Christopher M.; Rasmussen, Blake B.

2016-01-01

Aging impairs skeletal muscle protein synthesis, leading to muscle weakness and atrophy. However, the underlying molecular mechanisms remain poorly understood. Here, we review evidence that mTORC1- and ATF4-mediated amino acid sensing pathways, triggered by impaired amino acid delivery to aged skeletal muscle, may play important roles in skeletal muscle aging. Interventions that alleviate age-related impairments in muscle protein synthesis, strength and/or muscle mass appear to do so by reversing age-related changes in skeletal muscle amino acid delivery, mTORC1 activity and/or ATF4 activity. An improved understanding of the mechanisms and roles of amino acid sensing pathways in skeletal muscle may lead to evidence-based strategies to attenuate sarcopenia. PMID:27444066

Formation of Amino Acid Thioesters for Prebiotic Peptide Synthesis: Catalysis By Amino Acid Products

NASA Technical Reports Server (NTRS)

Weber, Arthur L.; DeVincenzi, Donald L. (Technical Monitor)

1999-01-01

The origin of life can be described as a series of events in which a prebiotic chemical process came increasingly under the control of its catalytic products. In our search for this prebiotic process that yielded catalytic takeover products (such as polypeptides), we have been investigating a reaction system that generates peptide-forming amino acid thioesters from formaldehyde, glycolaldehyde, and ammonia in the presence of thiols. As shown below, this model process begins by aldol condensation of formaldehyde and glycolaldehyde to give trioses and releases. These sugars then undergo beta-dehydration yielding their respective alpha-ketoaldehydes. Addition of ammonia to the alpha-ketoaldehydes yields imines which can either: (a) rearrange in the presence of thesis to give amino acid thioesters or (be react with another molecule of aldehyde to give imidazoles. This 'one-pot' reaction system operates under mild aqueous conditions, and like modem amino acid biosynthesis, uses sugar intermediates which are converted to products by energy-yielding redox reactions. Recently, we discovered that amino acids, such as the alanine reaction product, catalyze the first and second steps of the process. In the presence of ammonia the process also generates other synthetically useful products, like the important biochemical -- pyruvic acid.

Amino Acid Metabolism in Acute Renal Failure: Influence of Intravenous Essential L-Amino Acid Hyperalimentation Therapy

PubMed Central

Abel, Ronald M.; Shih, Vivian E.; Abbott, William M.; Beck, Clyde H.; Fischer, Josef E.

1974-01-01

A solution of 8 essential I-amino acids and hypertonic dextrose was administered to 5 patients in acute postoperative renal failure in a program of hyperalimentation designed to decrease the patient's catabolic state and to accrue certain metabolic benefits. A sixth patient receiving intravenous glucose alone served as a control. The pretreatment plasma concentrations of amino acids in all 6 patients did not differ significantly from normal; following intravenous essential amino acids at a dose of approximately 12.6 gm/24 hours, no significant elevations out of the normal range of these substances occurred. Since urinary excretion rates did not dramatically increase, urinary loss was excluded as a possible cause for the failure of increase of plasma concentrations. The results suggest that the administration of an intravenous solution of 1-amino acids and hypertonic dextrose is associated with rapid clearance from the blood of these substances and, with a failure of increased urinary excretion, indirect evidence of amino acid utilization for protein synthesis has been obtained. Histidine supplementation in patients with acute renal failure is probably unnecessary based on the lack of significant decreases in histidine concentrations in these patients. PMID:4850497

Amino acids derived from Titan tholins

NASA Technical Reports Server (NTRS)

Khare, B. N.; Sagan, C.; Ogino, H.; Nagy, B.; Er, C.; Schram, K. H.; Arakawa, E. T.

1986-01-01

An organic heteropolymer (Titan tholin) was produced by continuous dc discharge through a 0.9 N2/0.1 CH4 gas mixture at 0.2 mbar pressure, roughly simulating the cloudtop atmosphere of Titan. Treatment of this tholin with 6N HCl yielded 16 amino acids by gas chromatography after derivatization of N-trifluroacetyl isopropyl esters on two different capillary columns. Identifications were confirmed by GC/MS. Glycine, aspartic acid, and alpha- and beta-alanine were produced in greatest abundance; the total yield of amino acids was approximately 10(-2), approximately equal to the yield of urea. The presence of "nonbiological" amino acids, the absence of serine, and the fact that the amino acids are racemic within experimental error together indicate that these molecules are not due to microbial or other contamination, but are derived from the tholin. In addition to the HCN, HC2CN, and (CN)2 found by Voyager, nitriles and aminonitriles should be sought in the Titanian atmosphere and, eventually, amino acids on the surface. These results suggest that episodes of liquid water in the past or future of Titan might lead to major further steps in prebiological organic chemistry on that body.

Correlation between fibroin amino acid sequence and physical silk properties.

PubMed

Fedic, Robert; Zurovec, Michal; Sehnal, Frantisek

2003-09-12

The fiber properties of lepidopteran silk depend on the amino acid repeats that interact during H-fibroin polymerization. The aim of our research was to relate repeat composition to insect biology and fiber strength. Representative regions of the H-fibroin genes were sequenced and analyzed in three pyralid species: wax moth (Galleria mellonella), European flour moth (Ephestia kuehniella), and Indian meal moth (Plodia interpunctella). The amino acid repeats are species-specific, evidently a diversification of an ancestral region of 43 residues, and include three types of regularly dispersed motifs: modifications of GSSAASAA sequence, stretches of tripeptides GXZ where X and Z represent bulky residues, and sequences similar to PVIVIEE. No concatenations of GX dipeptide or alanine, which are typical for Bombyx silkworms and Antheraea silk moths, respectively, were found. Despite different repeat structure, the silks of G. mellonella and E. kuehniella exhibit similar tensile strength as the Bombyx and Antheraea silks. We suggest that in these latter two species, variations in the repeat length obstruct repeat alignment, but sufficiently long stretches of iterated residues get superposed to interact. In the pyralid H-fibroins, interactions of the widely separated and diverse motifs depend on the precision of repeat matching; silk is strong in G. mellonella and E. kuehniella, with 2-3 types of long homogeneous repeats, and nearly 10 times weaker in P. interpunctella, with seven types of shorter erratic repeats. The high proportion of large amino acids in the H-fibroin of pyralids has probably evolved in connection with the spinning habit of caterpillars that live in protective silk tubes and spin continuously, enlarging the tubes on one end and partly devouring the other one. The silk serves as a depot of energetically rich and essential amino acids that may be scarce in the diet.

Osmotic Pressure Simulations of Amino Acids and Peptides Highlight Potential Routes to Protein Force Field Parameterization

PubMed Central

Miller, Mark S.; Lay, Wesley K.

2016-01-01

Recent molecular dynamics (MD) simulations of proteins have suggested that common force fields overestimate the strength of amino acid interactions in aqueous solution. In an attempt to determine the causes of these effects, we have measured the osmotic coefficients of a number of amino acids using the AMBER ff99SB-ILDN force field with two popular water models, and compared the results with available experimental data. With TIP4P-Ew water, interactions between aliphatic residues agree well with experiment, but interactions of the polar residues serine and threonine are found to be excessively attractive. For all tested amino acids, the osmotic coefficients are lower when the TIP3P water model is used. Additional simulations performed on charged amino acids indicate that the osmotic coefficients are strongly dependent on the parameters assigned to the salt ions, with a reparameterization of the sodium:carboxylate interaction reported by the Aksimentiev group significantly improving description of the osmotic coefficient for glutamate. For five neutral amino acids, we also demonstrate a decrease in solute-solute attractions using the recently reported TIP4P-D water model and using the KBFF force field. Finally, we show that for four two-residue peptides improved agreement with experiment can be achieved by re-deriving the partial charges for each peptide. PMID:27052117

Biosensors for D-amino acid detection.

PubMed

Sacchi, Silvia; Rosini, Elena; Caldinelli, Laura; Pollegioni, Loredano

2012-01-01

The presence of D-amino acids in foods is promoted by harsh technological processes (e.g., high temperature or extreme pH values) or can be the consequence of adulteration or microbial contamination (D-amino acids are major components of the bacterial cell wall). For this reason, quality control is becoming more and more important both for the industry (as a cost factor) and for consumer protection. For routine food analysis and quality control, simple and easily applicable analytical methods are needed: biosensors can often satisfy these requirements. The use of an enzymatic, stereospecific reaction could confer selectivity to a biosensor for detecting and quantifying D-amino acids in foodstuffs. The flavoenzyme D-amino acid oxidase from the yeast Rhodotorula gracilis is an ideal biocatalyst for this kind of application because of its absolute stereospecificity, very high turnover number with various substrates, tight binding with the FAD cofactor, and broad substrate specificity. Furthermore, alterations in the local brain concentrations of D-serine (predominantly D-amino acid in the mammalian central nervous system) have been related to several neurological and psychiatric diseases. Therefore, quantifying this neuromodulator represents an important task in biological, medical, and pharmaceutical research. Recently, an enzymatic microbiosensor, also using R. gracilis D-amino acid oxidase as biocatalyst, was developed for detecting D-serine in vivo.

Benzylserine inhibits breast cancer cell growth by disrupting intracellular amino acid homeostasis and triggering amino acid response pathways.

PubMed

van Geldermalsen, Michelle; Quek, Lake-Ee; Turner, Nigel; Freidman, Natasha; Pang, Angel; Guan, Yi Fang; Krycer, James R; Ryan, Renae; Wang, Qian; Holst, Jeff

2018-06-26

Cancer cells require increased levels of nutrients such as amino acids to sustain their rapid growth. In particular, leucine and glutamine have been shown to be important for growth and proliferation of some breast cancers, and therefore targeting the primary cell-surface transporters that mediate their uptake, L-type amino acid transporter 1 (LAT1) and alanine, serine, cysteine-preferring transporter 2 (ASCT2), is a potential therapeutic strategy. The ASCT2 inhibitor, benzylserine (BenSer), is also able to block LAT1 activity, thus inhibiting both leucine and glutamine uptake. We therefore aimed to investigate the effects of BenSer in breast cancer cell lines to determine whether combined LAT1 and ASCT2 inhibition could inhibit cell growth and proliferation. BenSer treatment significantly inhibited both leucine and glutamine uptake in MCF-7, HCC1806 and MDA-MB-231 breast cancer cells, causing decreased cell viability and cell cycle progression. These effects were not primarily leucine-mediated, as BenSer was more cytostatic than the LAT family inhibitor, BCH. Oocyte uptake assays with ectopically expressed amino acid transporters identified four additional targets of BenSer, and gas chromatography-mass spectrometry (GCMS) analysis of intracellular amino acid concentrations revealed that this BenSer-mediated inhibition of amino acid uptake was sufficient to disrupt multiple pathways of amino acid metabolism, causing reduced lactate production and activation of an amino acid response (AAR) through activating transcription factor 4 (ATF4). Together these data showed that BenSer blockade inhibited breast cancer cell growth and viability through disruption of intracellular amino acid homeostasis and inhibition of downstream metabolic and growth pathways.

Network-Guided GWAS Improves Identification of Genes Affecting Free Amino Acids.

PubMed

Angelovici, Ruthie; Batushansky, Albert; Deason, Nicholas; Gonzalez-Jorge, Sabrina; Gore, Michael A; Fait, Aaron; DellaPenna, Dean

2017-01-01

Amino acids are essential for proper growth and development in plants. Amino acids serve as building blocks for proteins but also are important for responses to stress and the biosynthesis of numerous essential compounds. In seed, the pool of free amino acids (FAAs) also contributes to alternative energy, desiccation, and seed vigor; thus, manipulating FAA levels can significantly impact a seed's nutritional qualities. While genome-wide association studies (GWAS) on branched-chain amino acids have identified some regulatory genes controlling seed FAAs, the genetic regulation of FAA levels, composition, and homeostasis in seeds remains mostly unresolved. Hence, we performed GWAS on 18 FAAs from a 313-ecotype Arabidopsis (Arabidopsis thaliana) association panel. Specifically, GWAS was performed on 98 traits derived from known amino acid metabolic pathways (approach 1) and then on 92 traits generated from an unbiased correlation-based metabolic network analysis (approach 2), and the results were compared. The latter approach facilitated the discovery of additional novel metabolic interactions and single-nucleotide polymorphism-trait associations not identified by the former approach. The most prominent network-guided GWAS signal was for a histidine (His)-related trait in a region containing two genes: a cationic amino acid transporter (CAT4) and a polynucleotide phosphorylase resistant to inhibition with fosmidomycin. A reverse genetics approach confirmed CAT4 to be responsible for the natural variation of His-related traits across the association panel. Given that His is a semiessential amino acid and a potent metal chelator, CAT4 orthologs could be considered as candidate genes for seed quality biofortification in crop plants. © 2017 American Society of Plant Biologists. All Rights Reserved.

Amino acids precursors in lunar finds

NASA Technical Reports Server (NTRS)

Fox, S. W.; Harada, K.; Hare, P. E.; Hinsch, G.; Mueller, G.

1975-01-01

The consistent pattern is discussed of amino acids found in lunar dust from Apollo missions. The evidence indicates that compounds yielding amino acids were implanted into the surface of the moon by the solar wind, and the kind and amounts of amino acids found on the moon are closely similar to those found in meteorites. It is concluded that there is a common cosmochemical pattern for the moom and meteorites, and this offers evidence of a common course of cosmochemical reactions for carbon.

Amino Acid Degradation after Meteoritic Impact Simulation

NASA Technical Reports Server (NTRS)

Bertrand, M.; Westall, F.; vanderGaast, S.; Vilas, F.; Hoerz, F.; Barnes, G.; Chabin, A.; Brack, A.

2008-01-01

Amino acids are among the most important prebiotic molecules as it is from these precursors that the building blocks of life were formed [1]. Although organic molecules were among the components of the planetesimals making up the terrestrial planets, large amounts of primitive organic precursor molecules are believed to be exogenous in origin and to have been imported to the Earth via micrometeorites, carbonaceous meteorites and comets, especially during the early stages of the formation of the Solar System [1,2]. Our study concerns the hypothesis that prebiotic organic matter, present on Earth, was synthesized in the interstellar environment, and then imported to Earth by meteorites or micrometeorites. We are particularly concerned with the formation and fate of amino acids. We have already shown that amino acid synthesis is possible inside cometary grains under interstellar environment conditions [3]. We are now interested in the effects of space conditions and meteoritic impact on these amino acids [4-6]. Most of the extraterrestrial organic molecules known today have been identified in carbonaceous chondrite meteorites [7]. One of the components of these meteorites is a clay with a composition close to that of saponite, used in our experiments. Two American teams have studied the effects of impact on various amino acids [8,9]. [8] investigated amino acids in saturated solution in water with pressure ranges between 5.1 and 21 GPa and temperature ranges between 412 and 870 K. [9] studied amino acids in solid form associated with and without minerals (Murchison and Allende meteorite extracts) and pressure ranges between 3 and 30 GPa. In these two experiments, the amino acids survived up to 15 GPa. At higher pressure, the quantity of preserved amino acids decreases quickly. Some secondary products such as dipeptides and diketopiperazins were identified in the [8] experiment.

Amino Acids from a Comet

NASA Technical Reports Server (NTRS)

Cook, Jamie Elisla

2009-01-01

NASA's Stardust spacecraft returned samples from comet 81P/Wild 2 to Earth in January 2006. Examinations of the organic compounds in cometary samples can reveal information about the prebiotic organic inventory present on the early Earth and within the early Solar System, which may have contributed to the origin of life. Preliminary studies of Stardust material revealed the presence of a suite of organic compounds including several amines and amino acids, but the origin of these compounds (cometary- vs. terrestrial contamination) could not be identified. We have recently measured the carbon isotopic ratios of these amino acids to determine their origin, leading to the first detection of a coetary amino acid.

Computational structural analysis of an anti-l-amino acid antibody and inversion of its stereoselectivity

PubMed Central

Ranieri, Daniel I.; Hofstetter, Heike; Hofstetter, Oliver

2009-01-01

The binding site of a monoclonal anti-l-amino acid antibody was modeled using the program SWISS-MODEL. Docking experiments with the enantiomers of phenylalanine revealed that the antibody interacts with l-phenylalanine via hydrogen bonds and hydrophobic contacts, whereas the d-enantiomer is rejected due to steric hindrance. Comparison of the sequences of this antibody and an anti-d-amino acid antibody indicates that both immunoglobulins derived from the same germline progenitor. Substitution of four amino acids residues, three in the framework and one in the complementarity determining regions, allowed in silico conversion of the anti-l-amino acid antibody into an antibody that stereoselectively binds d-phenylalanine. PMID:19472280

BindML/BindML+: Detecting Protein-Protein Interaction Interface Propensity from Amino Acid Substitution Patterns.

PubMed

Wei, Qing; La, David; Kihara, Daisuke

2017-01-01

Prediction of protein-protein interaction sites in a protein structure provides important information for elucidating the mechanism of protein function and can also be useful in guiding a modeling or design procedures of protein complex structures. Since prediction methods essentially assess the propensity of amino acids that are likely to be part of a protein docking interface, they can help in designing protein-protein interactions. Here, we introduce BindML and BindML+ protein-protein interaction sites prediction methods. BindML predicts protein-protein interaction sites by identifying mutation patterns found in known protein-protein complexes using phylogenetic substitution models. BindML+ is an extension of BindML for distinguishing permanent and transient types of protein-protein interaction sites. We developed an interactive web-server that provides a convenient interface to assist in structural visualization of protein-protein interactions site predictions. The input data for the web-server are a tertiary structure of interest. BindML and BindML+ are available at http://kiharalab.org/bindml/ and http://kiharalab.org/bindml/plus/ .

Effects of alkali or acid treatment on the isomerization of amino acids.

PubMed

Ohmori, Taketo; Mutaguchi, Yuta; Doi, Katsumi; Ohshima, Toshihisa

2012-10-01

The effect of alkali treatment on the isomerization of amino acids was investigated. The 100×D/(D+L) values of amino acids from peptide increased with increase in the number of constituent amino acid residues. Furthermore, the N-terminal amino acid of a dipeptide was isomerized to a greater extent than the C-terminal residue. Copyright © 2012. Published by Elsevier B.V.

Relative reactivity of amino acids with chlorine in mixtures.

PubMed

Na, Chongzheng; Olson, Terese M

2007-05-01

The relative reactivity of chlorine with amino acids is an important determinant of the resulting chlorination products in systems where chlorine is the limiting reagent, for example, in the human gastrointestinal tract after consumption of chlorine-containing water, or during food preparation with chlorinated water. Since few direct determinations of the initial reactivity of chlorine with amino acids have been made, 17 amino acids were compared in this study using competitive kinetic principles. The experimental results showed that (1) most amino acids have similar initial reactivities at neutral pH; (2) amino acids with thiol groups such as methionine and cysteine are exceptionally reactive and produce sulfoxides; (3) amino acids without thiol groups primarily undergo monochlorination of the amino nitrogen; and (4) glycine and proline are the least reactive. Dichlorination was estimated to occur with approximately 26% of the amino acid groups when the total amino acid: chlorine concentrations were equal.

Unnatural reactive amino acid genetic code additions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Unnatural reactive amino acid genetic code additions

DOEpatents

Deiters, Alexander; Cropp, Ashton T; Chin, Jason W; Anderson, Christopher J; Schultz, Peter G

2013-05-21

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Unnatural reactive amino acid genetic code additions

DOEpatents

Deiters, Alexander [La Jolla, CA; Cropp, T Ashton [San Diego, CA; Chin, Jason W [Cambridge, GB; Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA

2011-02-15

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Unnatural reactive amino acid genetic code additions

DOEpatents

Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

2014-08-26

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Unnatural reactive amino acid genetic code additions

DOEpatents

Deiters, Alexander [La Jolla, CA; Cropp, T Ashton [Bethesda, MD; Chin, Jason W [Cambridge, GB; Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA

2011-08-09

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNAsyn-thetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

-HPLC determination of acidic d-amino acids and their N-methyl derivatives in biological tissues

PubMed Central

Tsesarskaia, Mara; Galindo, Erika; Szókán, Gyula; Fisher, George

2015-01-01

d-aspartate (d-Asp) and N-methyl-d-aspartate (NMDA) occur in the neuroendocrine systems of vertebrates and invertebrates where they play a role in hormone release and synthesis, neurotransmission, and memory and learning. N-methyl-d-glutamate (NMDG) has also been detected in marine bivalves. Several methods have been used to detect these amino acids, but they require pretreatment of tissue samples with o-phthaldialdehyde (OPA) to remove primary amino acids which interfere with the detection of NMDA and NMDG. We report here a one step derivatization procedure with the chiral reagent N-α-(5-fluoro-2,4-dinitrophenyl)-(d or l)-valine amide, FDNP-Val-NH2, a close analog of Marfey’s reagent but with better resolution and higher molar absorptivity. The diastereomers formed are separated by HPLC on an ODS-Hypersil column eluted with TFA/water – TFA/MeCN. UV absorption at 340 nm permits detection levels as low as 5–10 picomoles. D-Asp, NMDA and NMDG peaks are not obscured by other primary or secondary amino acids; hence pretreatment of tissues with OPA is not required. This method is highly reliable and fast (less than 40 minutes HPLC run). Using this method, we have detected D-Asp, NMDA and NMDG in several biological tissues (octopus brain, optical lobe, and bucchal mass; foot and mantle of the mollusk Scapharca broughtonii), confirming the results of other researchers. PMID:19277955

Interaction between lysine 102 and aspartate 338 in the insect amino acid cotransporter KAAT1.

PubMed

Castagna, M; Soragna, A; Mari, S A; Santacroce, M; Betté, S; Mandela, P G; Rudnick, G; Peres, A; Sacchi, V F

2007-10-01

KAAT1 is a lepidopteran neutral amino acid transporter belonging to the NSS super family (SLC6), which has an unusual cation selectivity, being activated by K(+) and Li(+) in addition to Na(+). We have previously demonstrated that Asp338 is essential for KAAT1 activation by K(+) and for the coupling of amino acid and driver ion fluxes. By comparing sequences of NSS family members, site-directed mutagenesis, and expression in Xenopus laevis oocytes, we identified Lys102 as a residue likely to interact with Asp338. Compared with wild type, the single mutants K102V and D338E each showed altered leucine uptake and transport-associated currents in the presence of both Na(+) and K(+). However, in K102V/D338E double mutant, the K102V mutation reversed both the inhibition of Na(+)-dependent transport and the block in K(+)-dependent transport that characterize the D338E mutant. K(+)-dependent leucine currents were not observed in any mutants with D338E. In the presence of the oxidant Cu(II) (1,10-phenanthroline)(3), we observed specific and reversible inhibition of K102C/D338C mutant, but not of the corresponding single cysteine mutants, suggesting that these residues are sufficiently close to form a disulfide bond. Thus both structural and functional evidence suggests that these two residues interact. Similar results have been obtained mutating the bacterial transporter homolog TnaT. Asp338 corresponds to Asn286, a residue located in the Na(+) binding site in the recently solved crystal structure of the NSS transporter LeuT(Aa) (41). Our results suggest that Lys102, interacting with Asp338, could contribute to the spatial organization of KAAT1 cation binding site and permeation pathway.

A Recessive Mutation Resulting in a Disabling Amino Acid Substitution (T194R) in the LHX3 Homeodomain Causes Combined Pituitary Hormone Deficiency

PubMed Central

Bechtold-Dalla Pozza, Susanne; Hiedl, Stefan; Roeb, Julia; Lohse, Peter; Malik, Raleigh E.; Park, Soyoung; Durán-Prado, Mario; Rhodes, Simon J.

2012-01-01

Background/Aims Recessive mutations in the LHX3 ho-meodomain transcription factor gene are associated with developmental disorders affecting the pituitary and nervous system. We describe pediatric patients with combined pituitary hormone deficiency (CPHD) who harbor a novel mutation in LHX3. Methods Two female siblings from related parents were examined. Both patients had neonatal complications. The index patient had CPHD featuring deficiencies of GH, LH, FSH, PRL, and TSH, with later onset of ACTH deficiency. She also had a hypoplastic anterior pituitary, respiratory distress, hearing impairment, and limited neck rotation. The LHX3 gene was sequenced and the biochemical properties of the predicted altered proteins were characterized. Results A novel homozygous mutation predicted to change amino acid 194 from threonine to arginine (T194R) was detected in both patients. This amino acid is conserved in the DNA-binding homeodomain. Computer modeling predicted that the T194R change would alter the homeodomain structure. The T194R protein did not bind tested LHX3 DNA recognition sites and did not activate the α-glycoprotein and PRL target genes. Conclusion The T194R mutation affects a critical residue in the LHX3 protein. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in the LHX3 gene. PMID:22286346

Amino acid analyses of Apollo 14 samples.

NASA Technical Reports Server (NTRS)

Gehrke, C. W.; Zumwalt, R. W.; Kuo, K.; Aue, W. A.; Stalling, D. L.; Kvenvolden, K. A.; Ponnamperuma, C.

1972-01-01

Detection limits were between 300 pg and 1 ng for different amino acids, in an analysis by gas-liquid chromatography of water extracts from Apollo 14 lunar fines in which amino acids were converted to their N-trifluoro-acetyl-n-butyl esters. Initial analyses of water and HCl extracts of sample 14240 and 14298 samples showed no amino acids above background levels.

A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning.

PubMed Central

Zeiner, M; Gehring, U

1995-01-01

In search of proteins which interact with activated steroid hormone receptors, we screened a human liver lambda gt11 expression library with the glucocorticoid receptor. We identified and cloned a cDNA sequence of 1322 bp that encodes a protein of 274 aa. This protein consists predominantly of hydrophilic amino acids and contains a putative bipartite nuclear localization signal. The in vitro translated receptor-associating protein runs in SDS/polyacrylamide gels with an apparent molecular mass of 46 kDa. By use of the bacterially expressed fusion protein with glutathione S-transferase we have found that interaction is not limited to the glucocorticoid receptor but included other nuclear receptors--most notably, the estrogen and thyroid receptors. Binding also occurs with the glucocorticoid receptor complexed with the antiglucocorticoid RU 38486, with the estrogen receptor complexed with the antiestrogen 4-hydroxytamoxifen or ICI 164,384, and even with receptors not complexed with ligand. Association with steroid hormone receptors depends on prior receptor activation--i.e., release from heat shock proteins. The sequence identified here appears to be a general partner protein for nuclear hormone receptors, with the gene being expressed in a variety of mammalian tissues. Images Fig. 2 Fig. 3 Fig. 4 PMID:8524784

Genetics of Amino Acid Taste and Appetite123

PubMed Central

Bosak, Natalia P; Glendinning, John I; Inoue, Masashi; Li, Xia; Manita, Satoshi; McCaughey, Stuart A; Murata, Yuko; Beauchamp, Gary K

2016-01-01

The consumption of amino acids by animals is controlled by both oral and postoral mechanisms. We used a genetic approach to investigate these mechanisms. Our studies have shown that inbred mouse strains differ in voluntary amino acid consumption, and these differences depend on sensory and nutritive properties of amino acids. Like humans, mice perceive some amino acids as having a sweet (sucrose-like) taste and others as having an umami (glutamate-like) taste. Mouse strain differences in the consumption of some sweet-tasting amino acids (d-phenylalanine, d-tryptophan, and l-proline) are associated with polymorphisms of a taste receptor, type 1, member 3 gene (Tas1r3), and involve differential peripheral taste responsiveness. Strain differences in the consumption of some other sweet-tasting amino acids (glycine, l-alanine, l-glutamine, and l-threonine) do not depend on Tas1r3 polymorphisms and so must be due to allelic variation in other, as yet unknown, genes involved in sweet taste. Strain differences in the consumption of l-glutamate may depend on postingestive rather than taste mechanisms. Thus, genes and physiologic mechanisms responsible for strain differences in the consumption of each amino acid depend on the nature of its taste and postingestive properties. Overall, mouse strain differences in amino acid taste and appetite have a complex genetic architecture. In addition to the Tas1r3 gene, these differences depend on other genes likely involved in determining the taste and postingestive effects of amino acids. The identification of these genes may lead to the discovery of novel mechanisms that regulate amino acid taste and appetite. PMID:27422518

Distribution, industrial applications, and enzymatic synthesis of D-amino acids.

PubMed

Gao, Xiuzhen; Ma, Qinyuan; Zhu, Hailiang

2015-04-01

D-Amino acids exist widely in microbes, plants, animals, and food and can be applied in pharmaceutical, food, and cosmetics. Because of their widespread applications in industry, D-amino acids have recently received more and more attention. Enzymes including D-hydantoinase, N-acyl-D-amino acid amidohydrolase, D-amino acid amidase, D-aminopeptidase, D-peptidase, L-amino acid oxidase, D-amino acid aminotransferase, and D-amino acid dehydrogenase can be used for D-amino acids synthesis by kinetic resolution or asymmetric amination. In this review, the distribution, industrial applications, and enzymatic synthesis methods are summarized. And, among all the current enzymatic methods, D-amino acid dehydrogenase method not only produces D-amino acid by a one-step reaction but also takes environment and atom economics into consideration; therefore, it is deserved to be paid more attention.

Regulation of the proteome by amino acids.

PubMed

Bourgoin-Voillard, Sandrine; Goron, Arthur; Seve, Michel; Moinard, Christophe

2016-03-01

Besides their main contribution as substrates for protein synthesis, amino acids as signaling molecules could exert some regulatory functions on protein synthesis and/or proteolysis that have been emphasized in a number of recent studies. Several publications have highlighted supplemental roles of those amino acids in protein metabolism as well as in immunity, heat shock response, or apoptosis processes. In this way, via their regulatory properties, selected amino acids (such as leucine, glutamine, arginine, citrulline, or methionine) directly influence the proteome. In this review, we are proposing an overview of the regulation of the proteome by amino acids in mammals. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interactions in the Metabolism of Glutamate and the Branched-Chain Amino Acids and Ketoacids in the CNS.

PubMed

Yudkoff, Marc

2017-01-01

Glutamatergic neurotransmission entails a tonic loss of glutamate from nerve endings into the synapse. Replacement of neuronal glutamate is essential in order to avoid depletion of the internal pool. In brain this occurs primarily via the glutamate-glutamine cycle, which invokes astrocytic synthesis of glutamine and hydrolysis of this amino acid via neuronal phosphate-dependent glutaminase. This cycle maintains constancy of internal pools, but it does not provide a mechanism for inevitable losses of glutamate N from brain. Import of glutamine or glutamate from blood does not occur to any appreciable extent. However, the branched-chain amino acids (BCAA) cross the blood-brain barrier swiftly. The brain possesses abundant branched-chain amino acid transaminase activity which replenishes brain glutamate and also generates branched-chain ketoacids. It seems probable that the branched-chain amino acids and ketoacids participate in a "glutamate-BCAA cycle" which involves shuttling of branched-chain amino acids and ketoacids between astrocytes and neurons. This mechanism not only supports the synthesis of glutamate, it also may constitute a mechanism by which high (and potentially toxic) concentrations of glutamate can be avoided by the re-amination of branched-chain ketoacids.

Antioxidant activity of amino acids in soybean oil at frying temperature: Structural effects and synergism with tocopherols.

PubMed

Hwang, Hong-Sik; Winkler-Moser, Jill K

2017-04-15

The purpose of this study was to evaluate amino acids as natural antioxidants for frying. Twenty amino acids were added to soybean oil heated to 180°C, and the effects of amino acid structure on the antioxidant activity were investigated. Amino acids containing a thiol, a thioether, or an extra amine group such as arginine, cysteine, lysine, methionine, and tryptophan had the strongest antioxidant activities. At 5.5mM, these amino acids had stronger antioxidant activities than 0.02% (1.1mM) tert-butylhydroquinone (TBHQ). A functional group such as an amide, carboxylic acid, imidazole, or phenol appeared to negatively affect amino acid antioxidant activity. Synergism between amino acids and tocopherols was demonstrated, and we found that this synergistic interaction may be mostly responsible for the antioxidant activity that was observed. In a frying study with potato cubes, 5.5mM l-methionine had significantly stronger antioxidant activity than 0.02% TBHQ. Published by Elsevier Ltd.

Insights into the Structure, Function, and Ligand Discovery of the Large Neutral Amino Acid Transporter 1, LAT1.

PubMed

Singh, Natesh; Ecker, Gerhard F

2018-04-24

The large neutral amino acid transporter 1 (LAT1, or SLC7A5) is a sodium- and pH-independent transporter, which supplies essential amino acids (e.g., leucine, phenylalanine) to cells. It plays an important role at the Blood⁻Brain Barrier (BBB) where it facilitates the transport of thyroid hormones, pharmaceuticals (e.g., l-DOPA, gabapentin), and metabolites into the brain. Moreover, its expression is highly upregulated in various types of human cancer that are characterized by an intense demand for amino acids for growth and proliferation. Therefore, LAT1 is believed to be an important drug target for cancer treatment. With the crystallization of the arginine/agmatine antiporter (AdiC) from Escherichia Coli , numerous homology models of LAT1 have been built to elucidate the substrate binding site, ligand⁻transporter interaction, and structure⁻function relationship. The use of these models in combination with molecular docking and experimental testing has identified novel chemotypes of ligands of LAT1. Here, we highlight the structure, function, transport mechanism, and homology modeling of LAT1. Additionally, results from structure⁻function studies performed on LAT1 are addressed, which have enhanced our knowledge of the mechanism of substrate binding and translocation. This is followed by a discussion on ligand- and structure-based approaches, with an emphasis on elucidating the molecular basis of LAT1 inhibition. Finally, we provide an exhaustive summary of different LAT1 inhibitors that have been identified so far, including the recently discovered irreversible covalent inhibitors.

Amino Acid-Assisted Incorporation of Dye Molecules within Calcite Crystals.

PubMed

Marzec, Bartosz; Green, David C; Holden, Mark A; Coté, Alexander S; Ihli, Johannes; Khalid, Saba; Kulak, Alexander; Walker, Daniel; Tang, Chiu; Duffy, Dorothy M; Kim, Yi-Yeoun; Meldrum, Fiona C

2018-05-23

Biomineralisation processes invariably occur in the presence of multiple organic additives, which act in combination to give exceptional control over structures and properties. However, few synthetic studies have investigated the cooperative effects of soluble additives. This work addresses this challenge and focuses on the combined effects of amino acids and coloured dye molecules. The experiments demonstrate that strongly coloured calcite crystals only form in the presence of Brilliant Blue R (BBR) and four of the seventeen soluble amino acids, as compared with almost colourless crystals using the dye alone. The active amino acids are identified as those which themselves effectively occlude in calcite, suggesting a mechanism where they can act as chaperones for individual molecules or even aggregates of dyes molecules. These results provide new insight into crystal-additive interactions and suggest a novel strategy for generating materials with target properties. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Apollo Program and Amino Acids

ERIC Educational Resources Information Center

Fox, Sidney W.

1973-01-01

Discusses the determination of hydrolyzable amino acid precursors and a group of six amino acids in the returned lunar samples of the Apollo programs. Indicates that molecular evolution is arrested at the precursor stage on the Moon because of lack of water. (CC)

Adsorption of various types of amino acids on the graphene and boron-nitride nano-sheet, a DFT-D3 study

NASA Astrophysics Data System (ADS)

Zhiani, Rahele

2017-07-01

The binding properties of the adsorption of five different classes of amino acids, namely, alanine (Ala), arginine (Arg), asparagine (Asn), histidine (His) and cysteine (Cys) on the surface of the graphene (Gra) and the born-nitride (BN) nano-sheet structures were studied from molecular viewpoint using quantum mechanics methods. Density functional theory (DFT) and DFT-D3 calculations were carried out to investigate the electronic properties and the dispersion interaction of the amino acid/adsorbent complexes. Several parameters affecting the interactions between the amino acids and the adsorbent surfaces such as solvent effect, adsorption energy and separation distance were investigated. Findings show that Arg forms the most stable complexes with the graphene and the BN nano-sheet compare to the other amino acids used in this study. The observed frequency results which were related to the band gap energies were consistent with the above statement. Results exhibit that adsorption of the amino acids on the surface of the BN nano-sheet and the graphene accompanied with the release of the energy. Calculations show that there are no bonded interactions between the amino acids and adsorbent surfaces. The polarity of the BN nano-sheet provides the more affinity towards the amino acids. These results were proved by the quantum chemistry studies.

Amino and fatty acids in carbonaceous meteorites

NASA Technical Reports Server (NTRS)

Kvenvolden, K. A.

1974-01-01

Analyses of two carbonaceous meteorites have provided much of the latest evidence which seems to support Oparin's theory on the origin of life. The meteorites involved are the Murray meteorite, which fell in 1950, and the Murchison meteorite, which fell in 1969. The amino acids in the two meteorites are similar in composition. Eight of the twenty amino acids found belong to amino acids present in proteins. A number of monocarboxylic and dicarboxylic fatty acids were also found in the meteorites.

Assorted interactions of amino acids prevailing in aqueous vitamin C solutions probed by physicochemical and ab-initio contrivances

NASA Astrophysics Data System (ADS)

Das, Koyeli; Roy, Milan Chandra; Rajbanshi, Biplab; Roy, Mahendra Nath

2017-11-01

Qualitative and quantitative analysis of molecular interaction prevailing in tyrosine and tryptophan in aqueous solution of vitamin C have been probed by thermophysical properties. The apparent molar volume (ϕV), viscosity B-coefficient, molal refraction (RM) of tyrosine and tryptophan have been studied in aqueous vitamin C solutions at diverse temperatures via Masson equation which deduced solute-solvent and solute-solute interactions, respectively. Spectroscopic study along with physicochemical and computational techniques provides lots of interesting and highly significant insights of the model biological systems. The overall results established strong solute-solvent interactions between studied amino acids and vitamin C mixture in the ternary solutions.

Functional map of arrestin-1 at single amino acid resolution.

PubMed

Ostermaier, Martin K; Peterhans, Christian; Jaussi, Rolf; Deupi, Xavier; Standfuss, Jörg

2014-02-04

Arrestins function as adapter proteins that mediate G protein-coupled receptor (GPCR) desensitization, internalization, and additional rounds of signaling. Here we have compared binding of the GPCR rhodopsin to 403 mutants of arrestin-1 covering its complete sequence. This comprehensive and unbiased mutagenesis approach provides a functional dimension to the crystal structures of inactive, preactivated p44 and phosphopeptide-bound arrestins and will guide our understanding of arrestin-GPCR complexes. The presented functional map quantitatively connects critical interactions in the polar core and along the C tail of arrestin. A series of amino acids (Phe375, Phe377, Phe380, and Arg382) anchor the C tail in a position that blocks binding of the receptor. Interaction of phosphates in the rhodopsin C terminus with Arg29 controls a C-tail exchange mechanism in which the C tail of arrestin is released and exposes several charged amino acids (Lys14, Lys15, Arg18, Lys20, Lys110, and Lys300) for binding of the phosphorylated receptor C terminus. In addition to this arrestin phosphosensor, our data reveal several patches of amino acids in the finger (Gln69 and Asp73-Met75) and the lariat loops (L249-S252 and Y254) that can act as direct binding interfaces. A stretch of amino acids at the edge of the C domain (Trp194-Ser199, Gly337-Gly340, Thr343, and Thr345) could act as membrane anchor, binding interface for a second rhodopsin, or rearrange closer to the central loops upon complex formation. We discuss these interfaces in the context of experimentally guided docking between the crystal structures of arrestin and light-activated rhodopsin.

Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids.

PubMed

Lager, Susanne; Jansson, Thomas; Powell, Theresa L

2014-10-15

Fatty acids are critical for normal fetal development but may also influence placental function. We have previously reported that oleic acid (OA) stimulates amino acid transport in primary human trophoblasts (PHTs). In other tissues, saturated and unsaturated fatty acids have distinct effects on cellular signaling, for instance, palmitic acid (PA) but not OA reduces IκBα expression. We hypothesized that saturated and unsaturated fatty acids differentially affect trophoblast amino acid transport and cellular signaling. To test this hypothesis, PHTs were cultured in docosahexaenoic acid (DHA; 50 μM), OA (100 μM), or PA (100 μM). DHA and OA were also combined to test whether DHA could counteract the OA stimulatory effect on amino acid transport. The effects of fatty acids were compared against a vehicle control. Amino acid transport was measured by isotope-labeled tracers. Activation of inflammatory-related signaling pathways and the mechanistic target of rapamycin (mTOR) pathway were determined by Western blot analysis. Exposure of PHTs to DHA for 24 h reduced amino acid transport and phosphorylation of p38 MAPK, STAT3, mTOR, eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein (rp)S6. In contrast, OA increased amino acid transport and phosphorylation of ERK, mTOR, S6 kinase 1, and rpS6. The combination of DHA with OA increased amino acid transport and rpS6 phosphorylation. PA did not affect amino acid transport but reduced IκBα expression. In conclusion, these fatty acids differentially regulated placental amino acid transport and cellular signaling. Taken together, these findings suggest that dietary fatty acids could alter the intrauterine environment by modifying placental function, thereby having long-lasting effects on the developing fetus. Copyright © 2014 the American Physiological Society.

Roles of plant hormones in the regulation of host-virus interactions.

PubMed

Alazem, Mazen; Lin, Na-Sheng

2015-06-01

Hormones are tuners of plant responses to biotic and abiotic stresses. They are involved in various complicated networks, through which they modulate responses to different stimuli. Four hormones primarily regulate plant defence to pathogens: salicylic acid (SA), jasmonic acid (JA), ethylene (Et) and abscisic acid (ABA). In susceptible plants, viral infections result in hormonal disruption, which manifests as the simultaneous induction of several antagonistic hormones. However, these antagonistic hormones may exhibit some sequential accumulation in resistant lines. Virus propagation is usually restricted by the activation of the small interfering RNA (siRNA) antiviral machinery and/or SA signalling pathway. Several studies have investigated these two systems, using different model viruses. However, the roles of hormones other than SA, especially those with antagonistic properties, such as ABA, have been neglected. Increasing evidence indicates that hormones control components of the small RNA system, which regulates many processes (including the siRNA antiviral machinery and the microRNA system) at the transcriptional or post-transcriptional level. Consequently, cross-talk between the antagonistic SA and ABA pathways modulates plant responses at multiple levels. In this review, we summarize recent findings on the different roles of hormones in the regulation of plant-virus interactions, which are helping us to elucidate the fine tuning of viral and plant systems by hormones. © 2014 THE AUTHORS. MOLECULAR PLANT PATHOLOGY PUBLISHED BY JOHN WILEY & SONS LTD AND BSPP.

The Origin of Amino Acids in Lunar Regolith Samples

NASA Technical Reports Server (NTRS)

Cook, Jamie E.; Callahan, Michael P.; Dworkin, Jason P.; Glavin, Daniel P.; McLain, Hannah L.; Noble, Sarah K.; Gibson, Everett K., Jr.

2016-01-01

We analyzed the amino acid content of seven lunar regolith samples returned by the Apollo 16 and Apollo 17 missions and stored under NASA curation since collection using ultrahigh-performance liquid chromatography with fluorescence detection and time-of-flight mass spectrometry. Consistent with results from initial analyses shortly after collection in the 1970s, we observed amino acids at low concentrations in all of the curated samples, ranging from 0.2 parts-per-billion (ppb) to 42.7 ppb in hot-water extracts and 14.5 ppb to 651.1 ppb in 6M HCl acid-vapor-hydrolyzed, hot-water extracts. Amino acids identified in the Apollo soil extracts include glycine, D- and L-alanine, D- and L-aspartic acid, D- and L-glutamic acid, D- and L-serine, L-threonine, and L-valine, all of which had previously been detected in lunar samples, as well as several compounds not previously identified in lunar regoliths: -aminoisobutyric acid (AIB), D-and L-amino-n-butyric acid (-ABA), DL-amino-n-butyric acid, -amino-n-butyric acid, -alanine, and -amino-n-caproic acid. We observed an excess of the L enantiomer in most of the detected proteinogenic amino acids, but racemic alanine and racemic -ABA were present in some samples.

Inhibitory activity and mechanism of inhibition of the N-[[(4-benzoylamino)phenyl]sulfonyl]amino acid aldose reductase inhibitors.

PubMed

DeRuiter, J; Mayfield, C A

1990-11-15

A series of substituted N-[[(4-benzoylamino)phenyl]sulfonyl]amino acids (BAPS-amino acids) were synthesized by established methods, and the stereochemistry of the products was confirmed by HPLC analysis after chiral derivatization. When tested against aldose reductase (alditol:NADP+ oxidoreductase; EC 1.1.1.21; ALR2) isolated from rat lens, all of the BAPS-amino acids were determined to be significantly more inhibitory than the corresponding N-(phenylsulfonyl)amino acids. Structure-inhibition and enzyme kinetic analyses suggest that the BAPS-amino acids inhibit ALR2 by a mechanism similar to the N-(phenylsulfonyl)amino acids. However, multiple inhibition analyses indicate that the increased inhibitory activity of the BAPS-amino acids is a result of interaction with multiple sites present on ALR2. Enzyme specificity studies with several of the BAPS-amino acids demonstrated that these compounds do not produce significant inhibition of other nucleotide-requiring enzymes including aldehyde reductase (alcohol: NADP+ oxidoreductase; EC 1.1.1.2; ALR1).

The role of microbial amino acid metabolism in host metabolism.

PubMed

Neis, Evelien P J G; Dejong, Cornelis H C; Rensen, Sander S

2015-04-16

Disruptions in gut microbiota composition and function are increasingly implicated in the pathogenesis of obesity, insulin resistance, and type 2 diabetes mellitus. The functional output of the gut microbiota, including short-chain fatty acids and amino acids, are thought to be important modulators underlying the development of these disorders. Gut bacteria can alter the bioavailability of amino acids by utilization of several amino acids originating from both alimentary and endogenous proteins. In turn, gut bacteria also provide amino acids to the host. This could have significant implications in the context of insulin resistance and type 2 diabetes mellitus, conditions associated with elevated systemic concentrations of certain amino acids, in particular the aromatic and branched-chain amino acids. Moreover, several amino acids released by gut bacteria can serve as precursors for the synthesis of short-chain fatty acids, which also play a role in the development of obesity. In this review, we aim to compile the available evidence on the contribution of microbial amino acids to host amino acid homeostasis, and to assess the role of the gut microbiota as a determinant of amino acid and short-chain fatty acid perturbations in human obesity and type 2 diabetes mellitus.

Effects of squat exercise and branched-chain amino acid supplementation on plasma free amino acid concentrations in young women.

PubMed

Shimomura, Yoshiharu; Kobayashi, Hisamine; Mawatari, Kazunori; Akita, Keiichi; Inaguma, Asami; Watanabe, Satoko; Bajotto, Gustavo; Sato, Juichi

2009-06-01

The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine:leucine:valine=1:2.3:1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism.

Antimicrobial peptides containing unnatural amino acid exhibit potent bactericidal activity against ESKAPE pathogens.

PubMed

Hicks, R P; Abercrombie, J J; Wong, R K; Leung, K P

2013-01-01

A series of 36 synthetic antimicrobial peptides containing unnatural amino acids were screened to determine their effectiveness to treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pnemoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens, which are known to commonly infect chronic wounds. The primary amino acid sequences of these peptides incorporate either three or six dipeptide units consisting of the unnatural amino acids Tetrahydroisoquinolinecarboxylic acid (Tic) and Octahydroindolecarboxylic acid (Oic). The Tic-Oic dipeptide units are separated by SPACER amino acids with specific physicochemical properties that control how these peptides interact with bacterial cell membranes of different chemical compositions. These peptides exhibited minimum inhibitory concentrations (MIC) against these pathogens in the range from >100 to 6.25 μg/mL. The observed diversity of MIC values for these peptides against the various bacterial strains are consistent with our hypothesis that the complementarity of the physicochemical properties of the peptide and the lipid of the bacteria's cell membrane determines the resulting antibacterial activity of the peptide. Published by Elsevier Ltd.

Altered peripheral amino acid profile indicate a systemic impact of active celiac disease and a possible role of amino acids in disease pathogenesis.

PubMed

Torinsson Naluai, Åsa; Saadat Vafa, Ladan; Gudjonsdottir, Audur H; Arnell, Henrik; Browaldh, Lars; Nilsson, Staffan; Agardh, Daniel

2018-01-01

We have previously performed a Genome Wide Association and linkage study that indicated a new disease triggering mechanism involving amino acid metabolism and nutrient sensing signaling pathways. The aim of this study was to investigate if plasma amino acid levels differed among children with celiac disease compared with disease controls. Fasting plasma samples from 141 children with celiac disease and 129 non-celiac disease controls, were analyzed for amino acid levels by liquid chromatography-tandem mass spectrometry (LC/MS). A general linear model using age and experimental effects as covariates was used to compare amino acid levels between children with a diagnosis of celiac disease and controls. Seven out of twenty-three analyzed amino acids were elevated in children with celiac disease compared with controls (tryptophan, taurine, glutamic acid, proline, ornithine, alanine and methionine). The significance of the individual amino acids do not survive multiple correction, however, multivariate analyses of the amino acid profile showed significantly altered amino acid levels in children with celiac disease overall and after correction for age, sex and experimental effects (p = 8.4 × 10-8). These findings support the idea that amino acids could influence systemic inflammation and play a possible role in disease pathogenesis.

21 CFR 172.320 - Amino acids.

Code of Federal Regulations, 2012 CFR

2012-04-01

... of total protein (expressed as free amino acid) L-Alanine 6.1 L-Arginine 6.6 L-Aspartic acid... DL-Methionine 3.1 L-Phenylalanine 5.8 L-Proline 4.2 L-Serine 8.4 L-Threonine 5.0 L-Tryptophan 1.6 L... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Amino acids. 172.320 Section 172.320 Food and...

21 CFR 172.320 - Amino acids.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of total protein (expressed as free amino acid) L-Alanine 6.1 L-Arginine 6.6 L-Aspartic acid... DL-Methionine 3.1 L-Phenylalanine 5.8 L-Proline 4.2 L-Serine 8.4 L-Threonine 5.0 L-Tryptophan 1.6 L... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Amino acids. 172.320 Section 172.320 Food and...

21 CFR 172.320 - Amino acids.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of total protein (expressed as free amino acid) L-Alanine 6.1 L-Arginine 6.6 L-Aspartic acid... DL-Methionine 3.1 L-Phenylalanine 5.8 L-Proline 4.2 L-Serine 8.4 L-Threonine 5.0 L-Tryptophan 1.6 L... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Amino acids. 172.320 Section 172.320 Food and...

21 CFR 172.320 - Amino acids.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of total protein (expressed as free amino acid) L-Alanine 6.1 L-Arginine 6.6 L-Aspartic acid... DL-Methionine 3.1 L-Phenylalanine 5.8 L-Proline 4.2 L-Serine 8.4 L-Threonine 5.0 L-Tryptophan 1.6 L... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Amino acids. 172.320 Section 172.320 Food and Drugs...

Identification of a novel amino acid racemase from a hyperthermophilic archaeon Pyrococcus horikoshii OT-3 induced by D-amino acids.

PubMed

Kawakami, Ryushi; Ohmori, Taketo; Sakuraba, Haruhiko; Ohshima, Toshihisa

2015-08-01

To date, there have been few reports analyzing the amino acid requirement for growth of hyperthermophilic archaea. We here found that the hyperthermophilic archaeon Pyrococcus horikoshii OT-3 requires Thr, Leu, Val, Phe, Tyr, Trp, His and Arg in the medium for growth, and shows slow growth in medium lacking Met or Ile. This largely corresponds to the presence, or absence, of genes related to amino acid biosynthesis in its genome, though there are exceptions. The amino acid requirements were dramatically lost by addition of D-isomers of Met, Leu, Val, allo-Ile, Phe, Tyr, Trp and Arg. Tracer analysis using (14)C-labeled D-Trp showed that D-Trp in the medium was used as a protein component in the cells, suggesting the presence of D-amino acid metabolic enzymes. Pyridoxal 5'-phosphate (PLP)-dependent racemase activity toward Met, Leu and Phe was detected in crude extract of P. horikoshii and was enhanced in cells grown in the medium supplemented with D-amino acids, especially D-allo-Ile. The gene encoding the racemase was narrowed down to one open reading frame on the basis of enzyme purification from P. horikoshii cells, and the recombinant enzyme exhibited PLP-dependent racemase activity toward several amino acids, including Met, Leu and Phe, but not Pro, Asp or Glu. This is the first report showing the presence in a hyperthermophilic archaeon of a PLP-dependent amino acid racemase with broad substrate specificity that is likely responsible for utilization of D-amino acids for growth.

Amino Acids 270 to 510 of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Are Required for Interaction with Receptor

PubMed Central

Babcock, Gregory J.; Esshaki, Diana J.; Thomas, William D.; Ambrosino, Donna M.

2004-01-01

A novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), has recently been identified as the causative agent of severe acute respiratory syndrome (SARS). SARS-CoV appears similar to other coronaviruses in both virion structure and genome organization. It is known for other coronaviruses that the spike (S) glycoprotein is required for both viral attachment to permissive cells and for fusion of the viral envelope with the host cell membrane. Here we describe the construction and expression of a soluble codon-optimized SARS-CoV S glycoprotein comprising the first 1,190 amino acids of the native S glycoprotein (S1190). The codon-optimized and native S glycoproteins exhibit similar molecular weight as determined by Western blot analysis, indicating that synthetic S glycoprotein is modified correctly in a mammalian expression system. S1190 binds to the surface of Vero E6 cells, a cell permissive to infection, as demonstrated by fluorescence-activated cell sorter analysis, suggesting that S1190 maintains the biologic activity present in native S glycoprotein. This interaction is blocked with serum obtained from recovering SARS patients, indicating that the binding is specific. In an effort to map the ligand-binding domain of the SARS-CoV S glycoprotein, carboxy- and amino-terminal truncations of the S1190 glycoprotein were constructed. Amino acids 270 to 510 were the minimal receptor-binding region of the SARS-CoV S glycoprotein as determined by flow cytometry. We speculate that amino acids 1 to 510 of the SARS-CoV S glycoprotein represent a unique domain containing the receptor-binding site (amino acids 270 to 510), analogous to the S1 subunit of other coronavirus S glycoproteins. PMID:15078936

Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choudhury, Kamalika Roy; Centre for Neuroscience, Indian Institute of Science, Bangalore 560012; Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com

2015-01-02

Highlights: • HYPK reduces mutant HTT-mediated aggregate formation and cytotoxicity. • Interaction of HYPK with HTT requires N-terminal 17 amino acid of HTT (HTT-N17). • Deletion of HTT-N17 leads to SDS-soluble, smaller, nuclear aggregates. • These smaller aggregates do not associate with HYPK and are more cytotoxic. • Maybe, interaction of HYPK with amphipathic HTT-N17 block HTT aggregate formation. - Abstract: Huntington’s disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminalmore » HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK.« less

The origin of amino acids in lunar regolith samples

NASA Astrophysics Data System (ADS)

Elsila, Jamie E.; Callahan, Michael P.; Dworkin, Jason P.; Glavin, Daniel P.; McLain, Hannah L.; Noble, Sarah K.; Gibson, Everett K.

2016-01-01

We analyzed the amino acid content of seven lunar regolith samples returned by the Apollo 16 and Apollo 17 missions and stored under NASA curation since collection using ultrahigh-performance liquid chromatography with fluorescence detection and time-of-flight mass spectrometry. Consistent with results from initial analyses shortly after collection in the 1970s, we observed amino acids at low concentrations in all of the curated samples, ranging from 0.2 parts-per-billion (ppb) to 42.7 ppb in hot-water extracts and 14.5-651.1 ppb in 6 M HCl acid-vapor-hydrolyzed, hot-water extracts. Amino acids identified in the Apollo soil extracts include glycine, D- and L-alanine, D- and L-aspartic acid, D- and L-glutamic acid, D- and L-serine, L-threonine, and L-valine, all of which had previously been detected in lunar samples, as well as several compounds not previously identified in lunar regoliths: α-aminoisobutyric acid (AIB), D- and L-β-amino-n-butyric acid (β-ABA), DL-α-amino-n-butyric acid, γ-amino-n-butyric acid, β-alanine, and ε-amino-n-caproic acid. We observed an excess of the L enantiomer in most of the detected proteinogenic amino acids, but racemic alanine and racemic β-ABA were present in some samples. We also examined seven samples from Apollo 15, 16, and 17 that had been previously allocated to a non-curation laboratory, as well as two samples of terrestrial dunite from studies of lunar module engine exhaust that had been stored in the same laboratory. The amino acid content of these samples suggested that contamination had occurred during non-curatorial storage. We measured the compound-specific carbon isotopic ratios of glycine, β-alanine, and L-alanine in Apollo regolith sample 70011 and found values of -21‰ to -33‰. These values are consistent with those seen in terrestrial biology and, together with the enantiomeric compositions of the proteinogenic amino acids, suggest that terrestrial biological contamination is a primary source of the

Evaluating Fmoc-amino acids as selective inhibitors of butyrylcholinesterase

PubMed Central

Gonzalez, Jeannette; Ramirez, Jennifer

2018-01-01

Cholinesterases are involved in neuronal signal transduction, and perturbation of function has been implicated in diseases, such as Alzheimer’s and Huntington’s disease. For the two major classes of cholinesterases, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), previous studies reported BChE activity is elevated in patients with Alzheimer’s disease, while AChE levels remain the same or decrease. Thus, the development of potent and specific inhibitors of BChE have received much attention as a potential therapeutic in the alleviation of neurodegenerative diseases. In this study, we evaluated amino acid analogs as selective inhibitors of BChE. Amino acid analogs bearing a 9-fluorenylmethyloxycarbonyl (Fmoc) group were tested, as the Fmoc group has structural resemblance to previously described inhibitors. We identified leucine, lysine, and tryptophan analogs bearing the Fmoc group as selective inhibitors of BChE. The Fmoc group contributed to inhibition, as analogs bearing a carboxybenzyl group showed ~tenfold higher values for the inhibition constant (KI value). Inclusion of a t-butoxycarbonyl on the side chain of Fmoc tryptophan led to an eightfold lower KI value compared to Fmoc tryptophan alone suggesting that modifications of the amino acid side chains may be designed to create inhibitors with higher affinity. Our results identify Fmoc-amino acids as a scaffold upon which to design BChE-specific inhibitors and provide the foundation for further experimental and computational studies to dissect the interactions that contribute to inhibitor binding. PMID:27522651

Evaluating Fmoc-amino acids as selective inhibitors of butyrylcholinesterase.

PubMed

Gonzalez, Jeannette; Ramirez, Jennifer; Schwans, Jason P

2016-12-01

Cholinesterases are involved in neuronal signal transduction, and perturbation of function has been implicated in diseases, such as Alzheimer's and Huntington's disease. For the two major classes of cholinesterases, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), previous studies reported BChE activity is elevated in patients with Alzheimer's disease, while AChE levels remain the same or decrease. Thus, the development of potent and specific inhibitors of BChE have received much attention as a potential therapeutic in the alleviation of neurodegenerative diseases. In this study, we evaluated amino acid analogs as selective inhibitors of BChE. Amino acid analogs bearing a 9-fluorenylmethyloxycarbonyl (Fmoc) group were tested, as the Fmoc group has structural resemblance to previously described inhibitors. We identified leucine, lysine, and tryptophan analogs bearing the Fmoc group as selective inhibitors of BChE. The Fmoc group contributed to inhibition, as analogs bearing a carboxybenzyl group showed ~tenfold higher values for the inhibition constant (K I value). Inclusion of a t-butoxycarbonyl on the side chain of Fmoc tryptophan led to an eightfold lower K I value compared to Fmoc tryptophan alone suggesting that modifications of the amino acid side chains may be designed to create inhibitors with higher affinity. Our results identify Fmoc-amino acids as a scaffold upon which to design BChE-specific inhibitors and provide the foundation for further experimental and computational studies to dissect the interactions that contribute to inhibitor binding.

6th Amino Acid Assessment Workshop

USDA-ARS?s Scientific Manuscript database

The focus of the 6th workshop is on lysine, arginine, and related amino acids. Functions, metabolic pathways, clinical uses, and upper tolerance intakes are emphasized in the articles that follow. Lysine is arguably the most deficient amino acid in the food supply of countries where poverty exists, ...

Combinatorics of aliphatic amino acids

NASA Astrophysics Data System (ADS)

Grützmann, Konrad; Böcker, Sebastian; Schuster, Stefan

2011-01-01

This study combines biology and mathematics, showing that a relatively simple question from molecular biology can lead to complicated mathematics. The question is how to calculate the number of theoretically possible aliphatic amino acids as a function of the number of carbon atoms in the side chain. The presented calculation is based on earlier results from theoretical chemistry concerning alkyl compounds. Mathematical properties of this number series are highlighted. We discuss which of the theoretically possible structures really occur in living organisms, such as leucine and isoleucine with a chain length of four. This is done both for a strict definition of aliphatic amino acids only involving carbon and hydrogen atoms in their side chain and for a less strict definition allowing sulphur, nitrogen and oxygen atoms. While the main focus is on proteinogenic amino acids, we also give several examples of non-proteinogenic aliphatic amino acids, playing a role, for instance, in signalling. The results are in agreement with a general phenomenon found in biology: Usually, only a small number of molecules are chosen as building blocks to assemble an inconceivable number of different macromolecules as proteins. Thus, natural biological complexity arises from the multifarious combination of building blocks.

Survival of Amino Acids in Micrometeorites During Atmospheric Entry

NASA Technical Reports Server (NTRS)

Glavin, Daniel P.; Bada, Jeffrey L.

2003-01-01

The delivery of amino acids by micrometeorites to the early Earth during the period of heavy bombardment could have been a significant source of the Earth's prebiotic amino acid inventory provided that these organic compounds survived atmospheric entry heating. To investigate the sublimation of amino acids from a micrometeorite analog at elevated temperature, grains from the CM-type carbonaceous chondrite Murchison were heated to 550 C inside a glass sublimation apparatus (SA) under reduced pressure. The sublimed residue that had collected on the cold finger of the SA after heating was analyzed for amino acids by HPLC. We found that when the temperature of the meteorite reached approx. 150 C, a large fraction of the amino acid glycine had vaporized from the meteorite, recondensed onto the end of the SA cold finger, and survived as the rest of the grains heated to 550 C. alpha-Aminoisobutryic acid and isovaline, which are two of the most abundant non-protein amino acids in Murchison, did not sublime from the meteorite and were completely destroyed during the heating experiment. Our experimental results suggest that sublimation of glycine present in micrometeorite grains may provide a way for this amino acid to survive atmospheric entry heating at temperatures less than 550 C; all other amino acids apparently are destroyed. Key Words: Amino acids-Exogenous delivery-Micrometeorites-Sublimation.

Molecular basis of essential amino acid transport from studies of insect nutrient amino acid transporters of the SLC6 family (NAT-SLC6)

PubMed Central

Boudko, Dmitri Y.

2012-01-01

Two protein families that represent major components of essential amino acid transport in insects have been identified. They are annotated as the SLC6 and SLC7 families of transporters according to phylogenetic proximity to characterized amino acid transporters (HUGO nomenclature). Members of these families have been identified as important apical and basolateral parts of transepithelial essential amino acid absorption in the metazoan alimentary canal. Synergistically, they play critical physiological roles as essential substrate providers to diverse metabolic processes, including generic protein synthesis. This review briefly clarifies the requirements for amino acid transport and a variety of amino acid transport mechanisms, including the aforementioned families. Further it focuses on the large group of Nutrient Amino acid Transporters (NATs), which comprise a recently identified subfamily of the Neurotransmitter Sodium Symporter family (NSS or SLC6). The first insect NAT, cloned from the caterpillar gut, has a broad substrate spectrum similar to mammalian B0 transporters. Several new NAT-SLC6 members have been characterized in an effort to explore mechanisms for the essential amino acid absorption in model dipteran insects. The identification and functional characterization of new B0-like and narrow specificity transporters of essential amino acids in fruit fly and mosquitoes leads to a fundamentally important insight: that NATs evolved and act together as the integrated active core of a transport network that mediates active alimentary absorption and systemic distribution of essential amino acids. This role of NATs is projected from the most primitive prokaryotes to the most complex metazoan organisms, and represents an interesting platform for unraveling the molecular evolution of amino acid transport and modeling amino acid transport disorders. The comparative study of NATs elucidates important adaptive differences between essential amino acid transportomes

Arrangement of Proteinogenic α-Amino Acids on a Cyclic Peptide Comprising Alternate Biphenyl-Cored ζ-Amino Acids.

PubMed

Tashiro, Shohei; Chiba, Masayuki; Shionoya, Mitsuhiko

2017-05-18

Aiming at precisely arranging several proteinogenic α-amino acids on a folded scaffold, we have developed a cyclic hexapeptide comprising an alternate sequence of biphenyl-cored ζ-amino acids and proteinogenic α-amino acids such as l-leucine. The amino acids were connected by typical peptide synthesis, and the resultant linear hexapeptide was intramolecularly cyclized to form a target cyclic peptide. Theoretical analyses and NMR spectroscopy suggested that the cyclic peptide was folded into an unsymmetrical conformation, and the structure was likely to be flexible in CHCl 3 . The optical properties including UV/Vis absorption, fluorescence, and circular dichroism (CD) were also evaluated. Furthermore, the cyclic peptide became soluble in water by introducing three carboxylate groups at the periphery of the cyclic skeleton. This α/ζ-alternating cyclic peptide is therefore expected to serve as a unique scaffold for arranging several functionalities. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Amino Acid Permeases and Virulence in Cryptococcus neoformans

PubMed Central

Takahashi, Juliana Possato Fernandes; Guerra, Juliana Mariotti; Santos, Dayane Cristina da Silva; Purisco, Sônia Ueda; Melhem, Márcia de Souza Carvalho; Fazioli, Raquel dos Anjos; Phanord, Clerlune; Sartorelli, Patrícia; Vallim, Marcelo A.

2016-01-01

Fungal opportunistic pathogens colonize various environments, from plants and wood to human and animal tissue. Regarding human pathogens, one great challenge during contrasting niche occupation is the adaptation to different conditions, such as temperature, osmolarity, salinity, pressure, oxidative stress and nutritional availability, which may constitute sources of stress that need to be tolerated and overcome. As an opportunistic pathogen, C. neoformans faces exactly these situations during the transition from the environment to the human host, encountering nutritional constraints. Our previous and current research on amino acid biosynthetic pathways indicates that amino acid permeases are regulated by the presence of the amino acids, nitrogen and temperature. Saccharomyces cerevisiae and Candida albicans have twenty-four and twenty-seven genes encoding amino acid permeases, respectively; conversely, they are scarce in number in Basidiomycetes (C. neoformans, Coprinopsis cinerea and Ustilago maydis), where nine to ten permease genes can be found depending on the species. In this study, we have demonstrated that two amino acid permeases are essential for virulence in C. neoformans. Our data showed that C. neoformans uses two global and redundant amino acid permeases, Aap4 and Aap5 to respond correctly to thermal and oxidative stress. Double deletion of these permeases causes growth arrest in C. neoformans at 37°C and in the presence of hydrogen peroxide. The inability to uptake amino acid at a higher temperature and under oxidative stress also led to virulence attenuation in vivo. Our data showed that thermosensitivity caused by the lack of permeases Aap4 and Aap5 can be remedied by alkaline conditions (higher pH) and salinity. Permeases Aap4 and Aap5 are also required during fluconazole stress and they are the target of the plant secondary metabolite eugenol, a potent antifungal inhibitor that targets amino acid permeases. In summary, our work unravels (i

New Functions and Potential Applications of Amino Acids.

PubMed

Uneyama, Hisayuki; Kobayashi, Hisamine; Tonouchi, Naoto

Currently, several types of amino acids are being produced and used worldwide. Nevertheless, several new functions of amino acids have been recently discovered that could result in other applications. For example, oral stimulation by glutamate triggers the cephalic phase response to prepare for food digestion. Further, the stomach and intestines have specific glutamate-recognizing systems in their epithelial mucosa. Regarding clinical applications, addition of monosodium glutamate to the medicinal diet has been shown to markedly enhance gastric secretion in a vagus-dependent manner. Branched-chain amino acids (BCAAs) are the major components of muscles, and ingestion of BCAAs has been found to be effective for decreasing muscle pain. BCAAs are expected to be a solution for the serious issue of aging. Further, ingestion of specific amino acids could be beneficial. Glycine can be ingested for good night's sleep: glycine ingestion before bedtime significantly improved subjective sleep quality. Ingestion of alanine and glutamine effectively accelerates alcohol metabolism, and ingestion of cystine and theanine effectively prevents colds. Finally, amino acids could be used in a novel clinical diagnostic method: the balance of amino acids in the blood could be an indicator of the risk of diseases such as cancer. These newly discovered functions of amino acids are expected to contribute to the resolution of various issues.

Determination of the presence of hyaluronic acid in preparations containing amino acids: the molecular weight characterization.

PubMed

Bellomaria, A; Nepravishta, R; Mazzanti, U; Marchetti, M; Piccioli, P; Paci, M

2014-10-15

Several pharmaceutical preparations contain hyaluronic acid in the presence of a large variety of low molecular weight charged molecules like amino acids. In these mixtures, it is particularly difficult to determine the concentration and the molecular weight of the hyaluronic acid fragments. In fact zwitterionic compounds in high concentration behave by masking the hyaluronic acid due to the electrostatic interactions between amino acids and hyaluronic acid. In such conditions the common colorimetric test of the hyaluronic acid determination appears ineffective and in the (1)H NMR spectra the peaks of the polymer disappear completely. By a simple separation procedure the presence of hyaluronic acid was revealed by the DMAB test and (1)H NMR while its average molecular weight in the final product was determined by DOSY NMR spectroscopy alone. The latter determination is very important due to the healthy effects of some sizes of this polymer's fragments. Copyright © 2014 Elsevier B.V. All rights reserved.

On the abiotic formation of amino acids. I - HCN as a precursor of amino acids detected in extracts of lunar samples. II - Formation of HCN and amino acids from simulated mixtures of gases released from lunar samples

NASA Technical Reports Server (NTRS)

Yuasa, S.; Flory, D.; Basile, B.; Oro, J.

1984-01-01

Two studies on the abiotic formation of amino acids are presented. The first study demonstrates the role of hydrogen cyanide as a precursor of amino acids detected in extracts of lunar samples. The formation of several amino acids, including glycine, alanine, aspartic acid, and glutamic acid, under conditions similar to those used for the analysis of lunar samples is demonstrated. The second study investigates the formation of hydrogen cyanide as well as amino acids from lunar-sample gas mixtures under electrical discharge conditions. These results extend the possibility of synthesis of amino acids to planetary bodies with primordial atmospheres less reducing than a mixture of methane, ammonia, hydrogen and water.

40 CFR 721.2584 - Dodecanoic acid, 12-amino-.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Dodecanoic acid, 12-amino-. 721.2584... Substances § 721.2584 Dodecanoic acid, 12-amino-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as dodecanoic acid, 12-amino- (PMN P-98-0823; CAS No. 693...

40 CFR 721.2584 - Dodecanoic acid, 12-amino-.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Dodecanoic acid, 12-amino-. 721.2584... Substances § 721.2584 Dodecanoic acid, 12-amino-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as dodecanoic acid, 12-amino- (PMN P-98-0823; CAS No. 693...

The impact of liquid preloads varying in macronutrient content on postprandial kinetics of amino acids relative to appetite in healthy adults.

PubMed

Korompokis, Konstantinos; Östman, Elin; Dougkas, Anestis

2016-12-01

The underlying mechanisms for the effect of proteins on appetite regulation, especially in presence of variable macronutrient composition, are not fully elucidated. The present study investigated the absorption kinetics of proteins after co-ingestion with the other macronutrients and examined the impact of circulating amino acids on appetite and satiety-related gut hormones. A randomized, within-subjects, 2-level full factorial design was implemented, where thirty six healthy subjects consumed seven preloads with similar energy density (3.1 kJ/g) and volume (670 mL) but with varying macronutrient content. The energy from protein (%) and the CHO:fat ratio were the two factors combined in three levels of 9, 24, 40 and 0.4, 2, 3.6 respectively. Blood and appetite parameters were evaluated until the serving of the ad libitum lunch after 210 min and the amino acid concentrations were measured in a subgroup of seven male subjects. The amino acid concentrations peaked at 90 min after all preloads and returned to the baseline values until 210 min. Protein intake affected amino acid profiles (P < 0.05), while no differences (P > 0.05) were detected between the two high protein preloads despite the different CHO:fat ratio (40%/0.4 CHO:fat and 40%/3.6 CHO:fat), indicating that neither carbohydrate nor fat influenced the profiles. Most of the amino acids were not related to appetite sensations or gut hormones (P > 0.05), while glutamate was positively associated with prospective consumption and inversely related to ghrelin (P < 0.05). Valine, leucine, isoleucine, lysine and α-aminobutyric acid were inversely associated with energy intake (P < 0.05). Overall, postprandial amino acid profiles were solely affected by protein content and were not consistently related to appetite regulation. Further investigation of glutamate's effect on appetite is needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Amino acids in modern and fossil woods

NASA Technical Reports Server (NTRS)

Lee, C.; Bada, J. L.; Peterson, E.

1976-01-01

The amino acid composition and the extent of racemization in several modern and fossil woods are reported. The method of analysis is described, and data are presented on the total amino acid concentration, the amino acid ratios, and the enantiomeric ratios in each sample. It is found that the amino acid concentration per gram of dry wood decreases with age of the sample, that the extent of racemization increases with increasing age, and that the amounts of aspartic acid, threonine, and serine decrease relative to valine with increasing age. The relative racemization rates of amino acids in wood, bone, and aqueous solution are compared, and it is shown that racemization in wood is much slower than in bone or aqueous solution. Racemization results for woods from the Kalambo Falls area of Zambia are used to calculate a minimum age of 110,000 years for the transition between the Sangoan and Acheulian industries at that site. This result is shown to be consistent with numerous radiometric dates for older Acheulian sites in Africa and to compare well with geologically inferred dates for the beginning of the Eemian and the end of the Acheulian industry in southern Africa.

The Impact of Single Amino Acids on Growth and Volatile Aroma Production by Saccharomyces cerevisiae Strains

PubMed Central

Fairbairn, Samantha; McKinnon, Alexander; Musarurwa, Hannibal T.; Ferreira, António C.; Bauer, Florian F.

2017-01-01

Nitrogen availability and utilization by Saccharomyces cerevisiae significantly influence fermentation kinetics and the production of volatile compounds important for wine aroma. Amino acids are the most important nitrogen source and have been classified based on how well they support growth. This study evaluated the effect of single amino acids on growth kinetics and major volatile production of two phenotypically different commercial wine yeast strains in synthetic grape must. Four growth parameters, lag phase, maximum growth rate, total biomass formation and time to complete fermentation were evaluated. In contrast with previous findings, in fermentative conditions, phenylalanine and valine supported growth well and asparagine supported it poorly. The four parameters showed good correlations for most amino acid treatments, with some notable exceptions. Single amino acid treatments resulted in the predictable production of aromatic compounds, with a linear correlation between amino acid concentration and the concentration of aromatic compounds that are directly derived from these amino acids. With the increased complexity of nitrogen sources, linear correlations were lost and aroma production became unpredictable. However, even in complex medium minor changes in amino acid concentration continued to directly impact the formation of aromatic compounds, suggesting that the relative concentration of individual amino acids remains a predictor of aromatic outputs, independently of the complexity of metabolic interactions between carbon and nitrogen metabolism and between amino acid degradation and utilization pathways. PMID:29312237

The Impact of Single Amino Acids on Growth and Volatile Aroma Production by Saccharomyces cerevisiae Strains.

PubMed

Fairbairn, Samantha; McKinnon, Alexander; Musarurwa, Hannibal T; Ferreira, António C; Bauer, Florian F

2017-01-01

Nitrogen availability and utilization by Saccharomyces cerevisiae significantly influence fermentation kinetics and the production of volatile compounds important for wine aroma. Amino acids are the most important nitrogen source and have been classified based on how well they support growth. This study evaluated the effect of single amino acids on growth kinetics and major volatile production of two phenotypically different commercial wine yeast strains in synthetic grape must. Four growth parameters, lag phase, maximum growth rate, total biomass formation and time to complete fermentation were evaluated. In contrast with previous findings, in fermentative conditions, phenylalanine and valine supported growth well and asparagine supported it poorly. The four parameters showed good correlations for most amino acid treatments, with some notable exceptions. Single amino acid treatments resulted in the predictable production of aromatic compounds, with a linear correlation between amino acid concentration and the concentration of aromatic compounds that are directly derived from these amino acids. With the increased complexity of nitrogen sources, linear correlations were lost and aroma production became unpredictable. However, even in complex medium minor changes in amino acid concentration continued to directly impact the formation of aromatic compounds, suggesting that the relative concentration of individual amino acids remains a predictor of aromatic outputs, independently of the complexity of metabolic interactions between carbon and nitrogen metabolism and between amino acid degradation and utilization pathways.

Amino acid catabolism and generation of volatiles by lactic acid bacteria.

PubMed

Tavaria, F K; Dahl, S; Carballo, F J; Malcata, F X

2002-10-01

Twelve isolates of lactic acid bacteria, belonging to the Lactobacillus, Lactococcus, Leuconostoc, and Enterococcus genera, were previously isolated from 180-d-old Serra da Estrela cheese, a traditional Portuguese cheese manufactured from raw milk and coagulated with a plant rennet. These isolates were subsequently tested for their ability to catabolize free amino acids, when incubated independently with each amino acid in free form or with a mixture thereof. Attempts were made in both situations to correlate the rates of free amino acid uptake with the numbers of viable cells. When incubated individually, leucine, valine, glycine, aspartic acid, serine, threonine, lysine, glutamic acid, and alanine were degraded by all strains considered; arginine tended to build up, probably because of transamination of other amino acids. When incubated together, the degradation of free amino acids by each strain was dependent on pH (with an optimum pH around 6.0). The volatiles detected in ripened Serra da Estrela cheese originated mainly from leucine, phenylalanine, alanine, and valine, whereas in vitro they originated mainly from valine, phenylalanine, serine, leucine, alanine, and threonine. The wild strains tested offer a great potential for flavor generation, which might justify their inclusion in a tentative starter/nonstarter culture for that and similar cheeses.

Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids

PubMed Central

Ilardo, Melissa; Meringer, Markus; Freeland, Stephen; Rasulev, Bakhtiyor; Cleaves II, H. James

2015-01-01

Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. We defined an adaptive set of amino acids as one whose members thoroughly cover relevant physico-chemical properties, or “chemistry space.” Using this metric, we compared the encoded amino acid alphabet to random sets of amino acids. These random sets were drawn from a computationally generated compound library containing 1913 alternative amino acids that lie within the molecular weight range of the encoded amino acids. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. Further analysis of more adaptive sets reveals common features and anomalies, and we explore their implications for synthetic biology. We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set. PMID:25802223

Regulation of intestinal health by branched-chain amino acids.

PubMed

Zhou, Hua; Yu, Bing; Gao, Jun; Htoo, John Khun; Chen, Daiwen

2018-01-01

Besides its primary role in the digestion and absorption of nutrients, the intestine also interacts with a complex external milieu, and is the first defense line against noxious pathogens and antigens. Dysfunction of the intestinal barrier is associated with enhanced intestinal permeability and development of various gastrointestinal diseases. The branched-chain amino acids (BCAAs) are important nutrients, which are the essential substrates for protein biosynthesis. Recently, emerging evidence showed that BCAAs are involved in maintaining intestinal barrier function. It has been reported that dietary supplementation with BCAAs promotes intestinal development, enhances enterocyte proliferation, increases intestinal absorption of amino acids (AA) and glucose, and improves the immune defenses of piglets. The underlying mechanism of these effects is mediated by regulating expression of genes and proteins associate with various signaling pathways. In addition, BCAAs promote the production of beneficial bacteria in the intestine of mice. Compelling evidence supports the notion that BCAAs play important roles in both nutrition and intestinal health. Therefore, as functional amino acids with various physiological effects, BCAAs hold key roles in promoting intestinal development and health in animals and humans. © 2017 Japanese Society of Animal Science.

Metabolomics method to comprehensively analyze amino acids in different domains.

PubMed

Gu, Haiwei; Du, Jianhai; Carnevale Neto, Fausto; Carroll, Patrick A; Turner, Sally J; Chiorean, E Gabriela; Eisenman, Robert N; Raftery, Daniel

2015-04-21

Amino acids play essential roles in both metabolism and the proteome. Many studies have profiled free amino acids (FAAs) or proteins; however, few have connected the measurement of FAA with individual amino acids in the proteome. In this study, we developed a metabolomics method to comprehensively analyze amino acids in different domains, using two examples of different sample types and disease models. We first examined the responses of FAAs and insoluble-proteome amino acids (IPAAs) to the Myc oncogene in Tet21N human neuroblastoma cells. The metabolic and proteomic amino acid profiles were quite different, even under the same Myc condition, and their combination provided a better understanding of the biological status. In addition, amino acids were measured in 3 domains (FAAs, free and soluble-proteome amino acids (FSPAAs), and IPAAs) to study changes in serum amino acid profiles related to colon cancer. A penalized logistic regression model based on the amino acids from the three domains had better sensitivity and specificity than that from each individual domain. To the best of our knowledge, this is the first study to perform a combined analysis of amino acids in different domains, and indicates the useful biological information available from a metabolomics analysis of the protein pellet. This study lays the foundation for further quantitative tracking of the distribution of amino acids in different domains, with opportunities for better diagnosis and mechanistic studies of various diseases.

Extraterrestrial Amino Acids in Ureilites Including Almahata Sitta