Monday, January 23, 2012

amino acid| What is amino acid|Papers on amino acid |Research on amino acid | Publications on amino acid


1.
J Biol Chem. 2012 Jan 18. [Epub ahead of print]

Functional characterization of a novel aquaporin from Dictyostelium discoideum amoebae implies a unique gating mechanism.

Source

University of Kiel, Germany;

Abstract

The social amoeba Dictyostelium discoideum is a widely used model organism for studying basic functions of protozoan and metazoan cells, such as osmoregulation and cell motility. There is evidence from other species that cellular water channels, aquaporins (AQP ), are central to both processes. Yet, data on D. discoideum AQPs is almost absent. Despite cloning of two putative D. discoideum AQPs, WacA and AqpA, water permeability has not been shown. Further, WacA and AqpA are expressed at the late multicellular stage and in spores but not in amoebae. We cloned a novel AQP, AqpB, from amoeboidal D. discoideum cells. Wildtype AqpB was impermeable to water, glycerol, and urea when expressed in Xenopus laevis oocytes. Neither stepwise truncation of the N-terminus nor selected point mutations activated the water channel. However, mutational truncation by 12 amino acids of an extraordinary long intracellular loop induced water permeability of AqpB hinting at a novel gating mechanism. This AqpB mutant was inhibited by mercuric chloride confirming the presence of a cysteine residue in the selectivity filter as predicted by our structure model. We detected AqpB by Western blot in a glycosylated and a non-glycosylated form throughout all developmental stages. When expressed in D. discoideum amoebae, AqpB-GFP fusion constructs localized to vacuolar structures, to the plasma membrane, and to lamellipodia-like membrane protrusions. We conclude, that the localization pattern in conjunction with channel gating may be indicative of AqpB functions in osmoregulation as well as cell motility of D. discoideum.

PMID:
22262860
[PubMed - as supplied by publisher]
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2.
J Biol Chem. 2012 Jan 18. [Epub ahead of print]

An amino-acid position at the crossroads of evolution of protein function: antibiotic-sensor domain of the BlaR1 protein from Staphylococcus aureus vs. class D β-lactamases.

Source

University of Notre Dame, United States.

Abstract

The integral-membrane protein BlaR1 of Staphylococcus aureus senses the presence of β-lactam antibiotics in the milieu, transduces the information to its cytoplasmic side, where its activity unleashes the expression of a set of genes, including that for BlaR1 itself, which manifest the antibiotic-resistant phenotype. The x-ray structure of the sensor domain of this protein exhibits an uncanny similarity to those of the class D β-lactamases. The former is a membrane-bound receptor/sensor for the β-lactam antibiotics, devoid of catalytic competence for substrate turnover, whereas the latter are soluble periplasmic enzymes in Gram-negative bacteria with avid ability for β-lactam turnover. The two are clearly related to each other from an evolutionary point of view. However, the high-resolution x-ray structures for both by themselves do not reveal why one is a receptor and the other an enzyme. It is documented herein that a single amino-acid change at position 439 of the BlaR1 protein is sufficient to endow the receptor/sensor protein with modest turnover ability for cephalosporins as substrates. The x-ray structure for this mutant protein and the dynamics simulations revealed how a hydrolytic water molecule may sequester itself in the antibiotic-binding site to enable hydrolysis of the acylated species. These studies document how the nature of the residue at position 439 is critical for the fate of the protein in imparting unique functions on the same molecular template, to result in one as a receptor and in another as a catalyst.

PMID:
22262858
[PubMed - as supplied by publisher]
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3.
J Biol Chem. 2012 Jan 18. [Epub ahead of print]

A Three-dimensional Structure of Steroid 21-Hydroxylase (Cytochrome P450 21A2) with Two Substrates Reveals Locations of Disease-associated Variants.

Source

Vanderbilt University, United States;

Abstract

Steroid 21-hydroxylase (cytochrome P450 21A2, CYP21A2) deficiency accounts for ~95% of individuals with congenital adrenal hyperplasia (CAH), a common autosomal recessive metabolic disorder of adrenal steroidogenesis. The effects ofamino acid mutations on CYP21A2 activity lead to impairment of the synthesis of cortisol and aldosterone and the excessive production of androgens. In order to understand the structural and molecular basis of this group of diseases, the bovine CYP21A2 crystal structure complexed with the substrate 17-hydroxyprogesterone (17OHP) was determined to 3.0 Å resolution. An intriguing result from this structure is that there are two molecules of 17OHP bound to the enzyme; the distal one being located at the entrance of the substrate access channel and the proximal one bound in the active site. The substrate binding features not only locate the key substrate recognition residues around the heme but also along the substrate access channel. In addition, orientation of the skeleton of the proximal molecule is toward the interior of the enzyme away from the substrate access channel. The 17OHP complex of CYP21A2 provides good relationship between the crystal structure, clinical data, and genetic mutants documented in the literature, thereby enhancing our understanding of CAH. In addition, the location of certain CYP21A2 mutations provides general understanding of structure/function relationships in P450s.

PMID:
22262854
[PubMed - as supplied by publisher]
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4.
J Biol Chem. 2012 Jan 19. [Epub ahead of print]

The substrate specificity of the two mitochondrial ornithine carriers can be swapped by a single mutation in the substrate binding site.

Source

University of Bari, Italy;

Abstract

Mitochondrial carriers are a large family of proteins that transport specific metabolites across the inner mitochondrial membrane. Sequence and structure analysis has indicated that these transporters have substrate binding sites in a similar location of the central cavity consisting of three major contact points. Here we have characterized mutations of the proposed substrate binding site in the human ornithine carriers ORC1 and ORC2 by carrying out transport assays with a set of different substrates. The different substrate specificities of the two isoforms, that share 87% identical amino acids, were essentially swapped by exchanging a single residue located at position 179 that is arginine in ORC1 and glutamine in ORC2. Altogether the substrate specificity changes demonstrate that R179 and E180 of contact point II bind the Cα carboxylate and amino group of the substrates, respectively. Residue E77 of contact point I most likely interacts with the terminal amino group of the substrate side chain. Furthermore, it is likely that all three contact points are involved in the substrate-induced conformational changes required for substrate translocation because R179 is probably connected with R275 of contact point III through W224 by cation-π interactions. Mutations at position 179 also affected the turnover number of the ornithine carrier severely, implying that substrate binding to residue 179 is a rate-limiting step of the catalytic transport cycle. Given that R179 is located in the vicinity of the matrix gate, it is concluded that it is a key residue in the opening of the carrier to the matrix side.

PMID:
22262851
[PubMed - as supplied by publisher]
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5.
J Biol Chem. 2012 Jan 18. [Epub ahead of print]

Essential roles of Raf/ERK/MAPK pathway, YY1, and Ca+2 influx in the growth arrest of human vascular smooth muscle cells by bilirubin.

Source

Beth Israel Deaconess Medical Center, Harvard Medical School, United States;

Abstract

The biological effects of bilirubin, still poorly understood, are concentration-dependent ranging from cell protection to toxicity. Here we present data that at high nontoxic physiological concentrations bilirubin inhibits growth of proliferating human coronary artery smooth muscle cells by three events. It impairs the activation of Raf/ERK/MAPK pathway and the cellular Raf and cyclin D1 content that results in retinoblastoma protein hypo-phosphorylation on amino acidsSer608 and Ser780. These events impede the release of YY1 to the nuclei and its availability to regulate the expression of genes and to support cellular proliferation. Moreover, altered calcium influx and calpain II protease activation leads to proteolytical degradation of transcription factor YY1. We conclude that in the serum stimulated human vascular smooth muscle primary cell cultures (hVSMC) bilirubin favors growth arrest and we propose that this activity is regulated by its interaction with the Raf/ERK/MAPK pathway, effect on cyclin D1 and Raf content, altered Rb profile of hypo-phosphorylation, calcium influx, and YY1 proteolysis. We propose that these activities together culminate in diminished 5S and 45S ribosomal RNA synthesis and cell growth arrest. The observations provide important mechanistic insight into the molecular mechanisms underlying the transition of human vascular smooth muscle cells from proliferative to contractile phenotype and the role of bilirubin in this transition.

PMID:
22262839
[PubMed - as supplied by publisher]
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6.
J Immunol. 2012 Jan 18. [Epub ahead of print]

A Proposed Algorithm Predictive for Cytotoxic T Cell Alloreactivity.

Source

Europdonor Foundation, Leiden 2333 BZ, The Netherlands.

Abstract

Previously, we showed that with an increasing number of amino acid differences in single HLA class I-mismatched molecules, the probability of T cell alloreactivity decreases. It is unlikely that every amino acid difference will affect T cell alloreactivity in a similar way; we hypothesized that the effect of an amino acid difference may be dependent on its position and/or physicochemical properties. We selected 131 patient/donor pairs with either a single HLA-A or -C mismatch in the graft-versus-host direction and that were compatible for HLA-B, -DRB1, and -DQB1. The alloreactive CTL precursor (CTLp) frequency was determined and associated with the amino acid differences between the single HLA class I mismatches. In the β sheet, only amino acids that are noncompatible in their physicochemical properties affect T cell alloreactivity, whereas in the α helices, both compatible and noncompatible amino acids affect CTLp outcome. Positions 62, 63, 73, 76, 77, 80, 99, 116, 138, 144, 147, and 163 were bivariately associated with CTLp outcome, irrespective of the total number of amino acid differences. In multivariate analysis, positions 62, 63, 73, 80, 116, 138, 144, and 163 were found to be most predictive for negative CTLp outcome. These results formed the basis for a weighted predictive mismatch score; pairs with the highest mismatch scores are estimated to be 13 times more likely to have a negative CTLp. This new algorithm may be a tool in donor selection for hematopoietic stem cell transplantation.

PMID:
22262656
[PubMed - as supplied by publisher]
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7.
Chemistry. 2012 Jan 19. doi: 10.1002/chem.201102816. [Epub ahead of print]

Dinucleosides with Non-Natural Backbones: A New Class of Ribonuclease A and Angiogenin Inhibitors.

Source

Department of Pharmaceutical Sciences, University of Tennessee, 847 Monroe, Johnson Bldg, Room 331, Memphis, Tennessee 38163 (USA).

Abstract

Ribonuclease A (RNase A) serves as a convenient model enzyme in the identification and development of inhibitors of proteins that are members of the ribonuclease superfamily. This is principally because the biological activity of these proteins, such as angiogenin, is linked to their catalytic ribonucleolytic activity. In an attempt to inhibit the biological activity of angiogenin, which involves new blood vessel formation, we employed different dinucleosides with varied non-natural backbones. These compounds were synthesized by coupling aminonucleosides with dicarboxylic acids andamino- and carboxynucleosides with an amino acid. These molecules show competitive inhibition with inhibition constant (K(i) ) values of (59±3) and (155±5) μM for RNase A. The compounds were also found to inhibit angiogenin in a competitive fashion with corresponding K(i) values in the micromolar range. The presence of an additional polar group attached to the backbone of dinucleosides was found to be responsible for the tight binding with both proteins. The specificity of different ribonucleolytic subsites were found to be altered because of the incorporation of a non-natural backbone in between the two nucleosidic moieties. In spite of the replacement of the phosphate group by non-natural linkers, these molecules were found to selectively interact with the ribonucleolytic site residues of angiogenin, whereas the cell binding site and nuclear translocation site residues remain unperturbed. Docked conformations of the synthesized compounds with RNase A and angiogenin suggest a binding preference for the thymine-adenine pair over the thymine-thymine pair.

Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:
22262583
[PubMed - as supplied by publisher]
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8.
Wiley Interdiscip Rev RNA. 2012 Jan 19. doi: 10.1002/wrna.1108. [Epub ahead of print]

Roles of tRNA in cell wall biosynthesis.

Source

Department of Microbiology, Ohio State University, Columbus, OH, USA.

Abstract

Recent research into various aspects of bacterial metabolism such as cell wall and antibiotic synthesis, degradation pathways, cellular stress, and amino acid biosynthesis has elucidated roles of aminoacyl-transfer ribonucleic acid (aa-tRNA) outside of translation. Although the two enzyme families responsible for cell wall modifications, aminoacyl-phosphatidylglycerol synthases (aaPGSs) and Fem, were discovered some time ago, they have recently become of intense interest for their roles in the antimicrobial resistance of pathogenic microorganisms. The addition of positively charged amino acids to phosphatidylglycerol (PG) by aaPGSs neutralizes the lipid bilayer making the bacteria less susceptible to positively charged antimicrobial agents. Fem transferases utilize aa-tRNA to form peptide bridges that link strands of peptidoglycan. These bridges vary among the bacterial species in which they are present and play a role in resistance to antibiotics that target the cell wall. Additionally, the formation of truncated peptides results in shorter peptide bridges and loss of branched linkages which makes bacteria more susceptible to antimicrobials. A greater understanding of the structure and substrate specificity of this diverse enzymatic family is necessary to aid current efforts in designing potential bactericidal agents. These two enzyme families are linked only by the substrate with which they modify the cell wall, aa-tRNA; their structure, cell wall modification processes and the physiological changes they impart on the bacterium differ greatly. WIREs RNA 2012. doi: 10.1002/wrna.1108 For further resources related to this article, please visit the WIREs website.

Copyright © 2012 John Wiley & Sons, Ltd.

PMID:
22262511
[PubMed - as supplied by publisher]
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9.
Mol Biol Cell. 2012 Jan 19. [Epub ahead of print]

The first luminal loop confers insulin responsiveness to the glucose transporter 4.

Source

Boston University School of Medicine, Boston, MA 02118.

Abstract

GLUT4 is the major glucose transporter which is regulated by insulin and is alone responsible for the effect of insulin on post-prandial blood glucose clearance. However, the nature of the insulin sensitivity of GLUT4 remains unknown. Here, we have replaced the first luminal loop of cellugyrin, the four-transmembrane protein that does not respond to insulin, with that of GLUT4. The chimera protein is targeted to the intracellular insulin-responsive vesicles and is translocated to the plasma membrane upon insulin stimulation. The faithful targeting of the chimera depends on the expression of the sorting receptor sortilin, that interacts with the unique amino acid residues in the first luminal loop of GLUT4. Thus, the first luminal loop may confer insulin responsiveness to the GLUT4 molecule.

PMID:
22262463
[PubMed - as supplied by publisher]
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10.
Methods Mol Biol. 2012;844:223-35.

Arginine and macrophage activation.

Source

Macrophage Biology Group, Institute for Research in Biomedicine (IRB Barcelona), and Departament de Fisiologia i Immunologia, Universitat de Barcelona, Barcelona, 08028, Spain.

Abstract

In order to perform their functions, macrophages must be activated either by Th1-type cytokines, such as interferon-gamma which is called classical activation or M1, or by Th2-type cytokines, such as IL-4, IL-10, IL-13, etc. referred as alternative activation or M2. In all of these conditions, macrophages require the uptake of exogenous arginine to meet their metabolic demands. Depending on the intracellular availability of this amino acid, the activities of these cells are differentially modulated. In this regard, macrophage activation requires this amino acid for the synthesis of proteins, production of nitric oxide via classical activation, and production of polyamines and proline through alternative activation. Therefore, the study of the arginine transport for amino acid system transporters may be a key regulatory step for physiological responses in macrophages. In this chapter, we present simple and direct methods to determine the mRNA expression and activity of arginine transporters. Moreover, we describe a direct method to measure the arginine catabolism using thin-layer chromatography.

PMID:
22262446
[PubMed - in process]
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11.
Angew Chem Int Ed Engl. 2012 Jan 19. doi: 10.1002/anie.201105016. [Epub ahead of print]

Reprogramming the Genetic Code: From Triplet to Quadruplet Codes.

Source

Medical Research Council Laboratory of Molecular Biology, Hills Rd, Cambridge, CB2 0QH (UK).

Abstract

The genetic code of cells is near-universally triplet, and since many ribosomal mutations are lethal, changing the cellular ribosome to read nontriplet codes is challenging. Herein we review work on the incorporation of unnatural amino acidsinto proteins in response to quadruplet codons, and the creation of an orthogonal translation system in the cell that uses an evolved orthogonal ribosome to efficiently direct the incorporation of unnatural amino acids in response to quadruplet codons. Using this system multiple distinct unnatural amino acids have been incorporated and used to genetically program emergent properties into recombinant proteins. Extension of approaches to incorporate multiple unnaturalamino acids may allow the combinatorial biosynthesis of materials and therapeutics, and drive investigations into whether life with additional genetically encoded polymers can evolve to perform functions that natural biological systems cannot.

Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:
22262408
[PubMed - as supplied by publisher]
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12.
Chemistry. 2012 Jan 19. doi: 10.1002/chem.201101416. [Epub ahead of print]

Template Effects in S(N) 2 Displacements for the Preparation of Pseudopeptidic Macrocycles.

Source

Departament de Química Inorgànica i Orgànica, Universitat Jaume I 12071 Castelló (Spain), Fax: (+34) 964-728-214.

Abstract

Macrocyclisation reactions of C(2) -symmetric pseudopeptides containing central pyridine-derived spacers are affected by the presence of different anions. The selection of the proper anion gives excellent results for the preparation of the corresponding macrocyclic structures. Kinetic studies show that the presence of those anions enhances both the yield and the rate of the reaction. Computational studies at the B3LYP/6-31G* level have allowed us to rationalise the experimental results. The obtained transition states (TSs) show that the interaction between the anion and the open-chain pseudopeptidic chain has a stabilising effect. The anion stabilises the two TSs involved: the first one, which involves the formation of the initial bond between the two subunits and leads to an open-chain intermediate, and the second one, which precedes the formation of the cyclic structure. The optimum anion (Br(-) when the central spacer is derived from 2,6-bis(aminomethyl)pyridine, is able to act as a template, in that it forces the two ends of the open-chain intermediate to approach each other by forming hydrogen bonds with the two amino acid subunits present in the intermediate. This stabilises the second TS to a greater extent than the first one, and thus, favours macrocyclisation over the competing oligomerisation reactions. The computational calculations also allowed us to predict the outcome of new experiments. Accordingly, the synthesis of the pseudopeptidic macrocycle derived from 2,6-diaminopyridine was not successful under the optimised conditions previously used. Nevertheless, calculations predicted that in this case Cl(-) should be more efficient than Br(-) , and this was subsequently experimentally confirmed. Interestingly, the presence of different substituents on the constituent amino acids seems to play a minor role in the overall process.

Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:
22262400
[PubMed - as supplied by publisher]
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13.
Molecules. 2012 Jan 19;17:1025-38.

Synthesis and Preliminary Antimicrobial Activities of New Arylideneamino-1,3,4-thiadiazole-(thio/dithio)-acetamido Cephalosporanic Acids.

Source

Department of Pharmaceutical Chemistry, College of Pharmacy, University of Baghdad, Bab-Al-muadham P.O. Box 14026, 10047, Baghdad, Iraq. shakmawales@yahoo.co.uk.

Abstract

New derivatives of 7-aminocephalosporanic acid 1-8 were synthesized by acylation of the 7-amino group of the cephem nucleus with various arylidinimino-1,3,4-thiadiazole-thio(or dithio)-acetic acid intermediates 3a-d and 5a-d, respectively, so the acyl side chains of these new cephalosporins contained a sulfide or disulfide bond. This unique combination of a Schiff base with the sulfide or disulfide bonds in the acyl side chain afforded new cephalosporins of reasonable potencies, some of which were found to possess moderate activities against the tested microorganisms. Their chemical structures were characterized by ¹H-NMR, IR spectroscopy and elemental microanalysis. Preliminary in vitro antimicrobial activities of the prepared cephalosporins were investigated using a panel of selected microorganisms. Results indicated that the newly synthesized cephalosporins containing disulfide bonds (compounds 5-8) exhibited better activities against Staphylococcus aureus and Escherichia coli. The cephalosporins cross-linked by a sulfide bond (compounds 1-4) showed a slight change in antimicrobial activities when compared with that of the reference cephalosporin (cephalexin).

PMID:
22262201
[PubMed - in process]
14.
Cell Cycle. 2012 Feb 1;11(3). [Epub ahead of print]

Spatial consequences of blocking mTOR/S6K:relevance for therapy.

Source

Institute of Medical Genetics; Medical University of Vienna; Vienna, Austria.

Abstract

Comment on: Rosner M, et al. Amino Acids 2011; In press.

PMID:
22262172
[PubMed - as supplied by publisher]
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15.
Microbiology. 2012 Jan 19. [Epub ahead of print]

The mating-related loci sexM and sexP of the zygomycetous fungus Mucor mucedo and their transcriptional regulation by trisporoid pheromones.

Source

Friedrich-Schiller-University.

Abstract

The putative mating type locus of mucoralean fungi consists of a single HMG-domain transcription factor gene, sexM or sexP, flanked by genes for an RNA helicase and a TP transporter. We used degenerated primers derived from the amino acid sequence of the RNA helicase for sequencing a fragment of this gene from Mucor mucedo. By inverse PCR this fragment was extended to obtain partial sequences of the sex loci from both mating types of Mucor mucedo. The sex loci in Mucor mucedo reflect the general picture obtained previously for Phycomyces blakesleeanus, presenting a single HMG-transcription factor gene, sexM in the minus and sexP in the plus mating type. These are located next to a gene for RNA helicase, too. Transcriptional analysis by quantitative real-time PCR showed that only transcription of sexM is considerably stimulated by adding trisporoid pheromones, thus mimicking sexual stimulation, whereas sexP is only slightly affected. These differences in regulation between sexM and sexP are supported by the observation that the promoter sequences controlling these genes show no similarities. The proteins structures themselves are considerably different. The SexM, but not the SexP protein harbours a nuclear localization sequence. The SexM protein is indeed transported to nuclei. This was shown by means of a GFP fusion construct that was used to study the localization of SexM in the yeast Saccharomyces cerevisiae. The fusion protein is highly enriched in nuclei.

PMID:
22262094
[PubMed - as supplied by publisher]
16.
Biotechnol Lett. 2012 Jan 20. [Epub ahead of print]

Biotransformation of ginsenosides Re and Rg1 into ginsenosides Rg2 and Rh1 by recombinant β-glucosidase.

Source

Department of Oriental Medicinal Material and Processing, College of Life Science, Korean Ginseng Center Most Valuable Product and Ginseng Genetic Resource Bank, Kyung-Hee University, Seocheon-dong, Giheung-gu, Yongin-si, Gyeonggi-do, 446-701, Republic of Korea, linhuk@hotmail.com.

Abstract

Ginsenosides Re and Rg1 were transformed by recombinant β-glucosidase (Bgp1) to ginsenosides Rg2 and Rh1, respectively. The bgp1 gene consists of 2,496 bp encoding 831 amino acids which have homology to the glycosyl hydrolase families 3 protein domain. Using 0.1 mg enzyme ml(-1) in 20 mM sodium phosphate buffer at 37°C and pH 7.0, the glucose moiety attached to the C-20 position of ginsenosides Re and Rg1, was removed: 1 mg ginsenoside Re ml(-1) was transformed into 0.83 mg Rg2 ml(-1) (100% molar conversion) after 2.5 h and 1 mg ginsenoside Rg1 ml(-1) was transformed into 0.6 mg ginsenoside Rh1 ml(-1) (78% molar conversion) in 15 min. Using Bgp1 enzyme, almost all initial ginsenosides Re and Rg1 were converted completely to ginsenosides Rg2 and Rh1. This is the first report of the conversion of ginsenoside Re to ginsenoside Rg2 and ginsenoside Rg1 to ginsenoside Rh1 using the recombinant β-glucosidase.

PMID:
22261865
[PubMed - as supplied by publisher]
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17.
Genet Med. 2011 Sep 9. doi: 10.1038/gim.0b013e31822dd91f. [Epub ahead of print]

Costello syndrome: a Ras/mitogen activated protein kinase pathway syndrome (rasopathy) resulting from HRAS germline mutations.

Source

Division of Medical Genetics, A. I. duPont Hospital for Children, Wilmington, Delaware, USA.

Abstract

Costello syndrome (OMIM# 218040) is a distinctive rare multisystem disorder comprising a characteristic coarse facial appearance, intellectual disabilities, and tumor predisposition. Although the diagnosis can be suspected clinically, confirmation requires identification of a heterozygous mutation in the proto-oncogene HRAS. In contrast to somatic oncogenic mutations in neoplasia, the Costello syndrome changes are typically introduced in the paternal germline. The predicted amino acid substitutions allow for constitutive or prolonged activation of the HRAS protein, resulting in dysregulation of the Ras/mitogen activated protein kinase pathway. Dysregulation of this signaling pathway is the disease mechanism shared among Costello syndrome and other rasopathies, including neurofibromatosis type 1, Noonan syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. The Ras/mitogen activated protein kinase pathway governs cell proliferation and differentiation, and its dysregulation affects cardiac and brain development, accounting for the significant overlap in physical and developmental differences and common medical problems among rasopathies. Unlike the genetically heterogeneous Noonan syndrome and cardio-facio-cutaneous syndrome, Costello syndrome is caused by HRAS mutations only. Patients, clinicians, and researchers may benefit from a multidisciplinary "rasopathy clinic," which serves patients with more common conditions such as Noonan syndrome and neurofibromatosis and those affected by rare conditions such as Costello syndrome.Genet Med advance online publication 9 September 2011.

PMID:
22261753
[PubMed - as supplied by publisher]
18.
Nutrition. 2012 Jan 18. [Epub ahead of print]

High-carbohydrate/low-protein-induced hyperinsulinemia does not improve protein balance in children after cardiac surgery.

Source

Pediatric Intensive Care Department, Emma Children's Hospital/Academic Medical Center, Amsterdam, Netherlands.

Abstract

OBJECTIVE:

In pediatric cardiac surgery, fluid-restricted low-protein (LoProt) diets account for cumulative protein deficits with increased morbidity. In this setting, we aimed to inhibit proteolysis by a high-carbohydrate (HiCarb)-intake-induced hyperinsulinemia and improve protein balance.

METHODS:

The effect of a HiCarb/LoProt (glucose 10 mg · kg(-1) · min(-1)/protein 0.7 g · kg(-1) · d(-1)) versus a normal-carbohydrate (NormCarb)/LoProt (glucose 7.5 mg · kg(-1) · min(-1)/protein 0.3 g · kg(-1) · d(-1)) enteral diet on whole-body protein breakdown and balance was compared in a prospective, randomized, single-blinded trial in 24 children after cardiac surgery. On the second postoperative day, plasma insulin and amino acid concentrations, protein breakdown (endogenous rate of appearance of valine), protein synthesis (non-oxidative disposal of valine), protein balance, and the rate of appearance of urea were measured by using an isotopic infusion of [1-(13)C]valine and [(15)N(2)]urea.

RESULTS:

The HiCarb/LoProt diet led to a serum insulin concentration that was three times higher than the NormCarb/LoProt diet (596 pmol/L, 80-1833, and 198 pmol/L, 76-1292, respectively, P = 0.02), without differences in plasma glucose concentrations. There were no differences in plasma amino acid concentrations, non-oxidative disposal of valine, and endogenous rate of appearance of valine between the groups, with a negative valine balance in the two groups (-0.65 μmol · kg(-1) · min(-1), -1.91 to 0.01, and -0.58 μmol · kg(-1) · min(-1), -2.32 to -0.07, respectively, P = 0.71). The serum cortisol concentration in the HiCarb/LoProt group was lower compared with the NormCarb/LoProt group (204 nmol/L, 50-544, and 532 nmol/L, 108-930, respectively, P = 0.02).

CONCLUSION:

In children with fluid restriction after cardiac surgery, a HiCarb/LoProt diet compared with a NormCarb/LoProt diet stimulates insulin secretion but does not inhibit proteolysis further and therefore cannot be advocated for this purpose.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
22261573
[PubMed - as supplied by publisher]
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19.
Nutrition. 2012 Jan 18. [Epub ahead of print]

Plasma glutathione of HIV(+) patients responded positively and differently to dietary supplementation with cysteine or glutamine.

Source

Department of Public Health, Botucatu Medical School, UNESP-São Paulo State University, Botucatu, São Paulo, Brazil.

Abstract

OBJECTIVE:

Patients with positivity for the human immunodeficiency virus (HIV(+)) present low concentrations of antioxidant nutrients, including total glutathione (GSH) and its precursors. We investigated the responses of the sulfur-containing amino acid pathway to cysteine and glutamine (Gln) dietary supplements in patients with HIV(+) compared with healthy controls.

METHODS:

Twelve treated patients (six men and six women, 22-45 y old) and 20 healthy controls (10 men and 10 women, 20-59 y old) were randomly assigned to 7-d dietary supplements containing N-acetylcysteine (NAC; 1 g/d) or Gln (20 g/d), with a 7-d washout period ingesting their usual diet. Blood samples were drawn after an overnight fast. High-performance liquid chromatographic plasma analysis of sulfur-containing amino acids (methionine, homocysteine, cysteine, and taurine), GSH, oxidized GSH, and serine, glycine, glutamic acid, and Gln was carried out moments before and after 7-d supplementations. Statistical comparisons were undertaken between groups and between dietary supplements (P < 0.05).

RESULTS:

Patients with HIV(+) showed higher oxidized GSH and lower concentrations of GSH and all amino acidsexcept homocysteine. The HIV(+) group responded to the NAC by increased levels of sulfur-containing amino acids and GSH and equalized taurine and GSH levels in the control group. The Gln supplements also equalized the levels of GSH, Gln, and glycine in the control group.

CONCLUSION:

An increase in GSH may be attained by NAC or Gln supplementation, with NAC acting by increasing cysteine levels and Gln likely acting by replenishing the glycine pool (trial registered at http://www.clinicaltrials.gov, identifier NCT00910442).

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
22261571
[PubMed - as supplied by publisher]
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20.
Early Hum Dev. 2012 Jan 17. [Epub ahead of print]

The nutrition of preterm infants.

Source

Dipartimento di Pediatria e Neuropsichiatria Infantile, Università di Roma La Sapienza, Rome, Italy.

Abstract

Although great efforts have been made to improve neonatal nutrition in very low birthweight (VLBW) infants, many do not receive adequate nutrient intake and thus develop extrauterine growth restriction. In order to minimize the interruption of nutrients that occurs at birth, an "aggressive" nutritional approach has been proposed. Parenteral nutrition, which allows the infant's requirements for growth and development to be met, is indicated in infants for whom feeding via the enteral route is impossible, inadequate, or hazardous. In the last few years, great attention has been given to high amino acidsupply in VLBW infants from the first day of life in order to avoid catabolism, establish anabolism, achieve in utero protein accretion rates, and promote linear growth. Whenever possible, enteral feeding should commence with human milk, which is the preferred feeding method for all infants, including those born preterm. In order to meet the unique nutritional requirements of VLBW infants and preserve the singular benefit of breastfeeding, human milk should be fortified to allow adequate growth and bone mineralization. When feeding of preterm infants with human milk is impossible or extremely limited, cow-milk-based formulas for preterm infants must be used.

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