DOCSLIB.ORG

Of the Same Glycine Residue by Arginine and Glutamic Acid Residues

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Of the Same Glycine Residue by Arginine and Glutamic Acid Residues VOL. 48, 1962 GENETICS: HENNING AND YANOFSKY 1497 of their data with ours indicates that the phenomenon described herein is most likely due to the combination of ma-i + and ry+ subunits. We have also observed reactivation of "inactive" xanthine dehydrogenase of wild-type Drosophila. II Forrest, H. S., E. W. Hanly, and J. M. Lagowski, Genetics, 56, 1455 (1961). 12Horowitz, N., personal communication. 13 Hadorn, E., and I. Schwink, Nature, 177, 940 (1956); Glassman, E., Dros. Inform. Service, 31, 121 (1957). '4Glassman, E., and W. Pinkerton, Science, 131, 1810 (1960). AMINO ACID REPLACEMENTS ASSOCIATED WITH REVERSION AND RECOMBINA TION WITHIN THE A GENE* BY ULF HENNINGt AND CHARLES YANOFSKY DEPARTMENT OF BIOLOGICAL SCIENCES, STANFORD UNIVERSITY, STANFORD, CALIFORNIA Communicated by V. C. Twitty, July 26, 1962 Studies with the A protein of the tryptophan synthetase of Escherichia coli have established that mutationally altered sites that are located at or near the same position in the A gene lead to amino acid substitutions in the same tryptic peptide of the A protein." 2 It has also been shown that two mutants, strains A23 and A46, with alterations extremely close to one another on the genetic map, form A proteins that are distinguishable from the wild-type A protein by the replacement of the same glycine residue by arginine and glutamic acid residues, respectively.1 2 It was concluded from these findings that the mutational alteration characteristic of each of the mutants involved a different nucleotide in the same amino acid coding unit in the A gene. 1 2 Mutants A23 and A46 revert spontaneously to tryptophan independence. Some of the strains obtained, termed full revertants, are phenotypically indistinguishable from the wild type, while others, termed partial revertants, grow slowly without tryptophan supplementation. The mutations resulting in partial reversion may occur at the same site as the original mutation (primary site reversion), or at a second site in the A gene.3' 4 The present report is concerned with a study of a primary site partial revertant and several full revertants of mutant A46, and full revertants derived from two iden- tical mutants, A23 and A28. The results obtained demonstrate that any one of four different amino acids can occupy a certain position in the A protein and the protein will be functional. It is also shown that recombinants obtained from crosses between some of the strains form A proteins with different amino acids at a particular position in the A protein than the amino acids present at the same position in the A proteins of the parental strains. Materials and Methods.-Bacterial strains: Mutants A23, A28, and A46, ob- tained by penicillin selection6 following ultraviolet irradiation of E. coli K-12, have been described in detail elsewhere." 2, 7 The full and partial revertants studied were spontaneous revertants.3, 5 Genetic procedures: The methods employed for the preparation of transducing lysates of phage Plkc and for transduction with this phage have been described Downloaded by guest on September 28, 2021 1498 GENETICS: HENNING AND YANOFSKY PROC. N. A. S. by Lennox.8 In order to virtually exclude the carry-over of transducing phage with the wild-type tryptophan region, all lysates were prepared with phage that was grown on the donor strain. The use of cys- tryp- recipients for recombina- tional analyses has been discussed previously.7 Isolation of peptides and amino acid analyses: The procedures used for the isolation of the A protein,9 as well as the methods used for the digestion of the protein with trypsin and chymotrypsin,1' the isolation of peptides,2"1' and the analysis of peptides have been described previously." 2 Results. Characteristics of strain A46PR9 and the full revertants derived from mu- tants A46, A23, and A28: The characteristics of the revertant strains examined in this study are summarized in Table 1. With the exception of partial revertant A46PR9, the strains are indistinguishable from the wild type. As reported pre- viously,3 the A protein of strain A46PR9 is only about 1/1,000 as active as the wild- type strain in the physiologically important reaction, the conversion of indolegly- cerol phosphate to tryptophan. The A proteins of all the revertants studied TABLE 1 CHARACTERISTICS OF REVERTANTS OF MUTANTS A23 AND A46 Generation Accumulation Specific activity time, of of Strain Colony size* minutes* indoleglycerol A protein: wild type - 70-72 - 2 A46 auxotroph auxotroph +t 31t A46PR9 2/3 of wild type 84 + 91 A46FR1 = wild type 70-72 - 2.2 A46FR2 = wild type 70-72 - 2.1 A23 auxotroph auxotroph + t 23 t A23FR1 = wild type 70 - 2.1 A23FR2 = wild type 70 - 1.9 A28FR1 = wild type 70 - 1.9 * On glucose-minimal medium at 370C. t Grown on limiting amounts of indole (2.5 jig/nml). I In the conversion of indole to tryptophan. have the same electrophoretic mobility as the wild-type protein in polyacrylamide gel"2 at pH 9.5.13 The A46 protein is more negatively charged under the same conditions. This behavior is consistent with the amino acid substitution in this protein, glycine to glutamic acid. The charge of the A23 protein could not be determined in polyacrylamide gel, presumably because of its extreme lability.'3 The A23 protein would be expected to be more positively charged than the wild- type protein. The mobilities of the revertant proteins suggest that in each case a charged amino acid was replaced by an amino acid with a side chain that is not charged at pH 9.5. Examination of the A46PR9, A46FR1, and A4f6FR2 tryptic peptides corresponding to the tryptic peptide altered in mutant A46: Tryptic peptide TP3 was isolated from digests of the A46PR9, A46FR1, and A46FR2 proteins. The amino acid composi- tion of these three peptides is compared with the composition of the corresponding wild-type and A46 peptides in Table 2. The analyses show that one glutamic acid or glutamine residue present in the A46 peptide is replaced by a valine residue in the peptide from A46PR9, by an alanine residue in the peptide from A46FR1, and by a glycine residue in the peptide isolated frcm A46FR2. As described pre- viously,2 chymotryptic hydrolysis of peptide TP3 gives three peptides, designated Downloaded by guest on September 28, 2021 VOL. 48, 1962 GENETICS: HENNING AND YANOFSKY 1499 TP3C1, TP3C2, and TP3C3. These - three peptides were isolated from chy- O . Oj O motryptic digests of TP3 from the par- tial revertant and the two full revertants of A46. The amino acid analyses of these R+g R. peptides (Table 2) showed that in all cases peptide TP3C1 contained the amino - acid substitution. Since both glutamic coRoO° acid and glutamine residues were present ¢a in TP3C1 from the A protein of mutant 0 A46, it was not possible to decide from ¢ the analyses alone whether the glutamic W e A acid residue or the glutamine residue was >- ¢ E replaced in the peptides from the revert- - eq ,^ V_ oooo0 0 C eq ants. It had been deduced" 2 from pre- : ..H - vious experiments that the glycine in g, TP3C1 from the wild-type protein was Z ¢ >, t replaced by arginine in peptide TP3C1 00° --4 °s 4 from strain A23. Since the glycine in the be wild-type peptide is also replaced by glu- tamic acid in peptide TP3C1 from mutant 2 0 A46, it was assumed that glycine, argin- v) ine, and glutamic acid occupy the same w position in these different proteins. Ex- Q a) periments using carboxypeptidase diges- ¢¢d tion of the TP3C1 peptide from the vari- z ous proteins have now verified this as- COO. sumption.15 The same studies have Eq , shown that the valine, alanine, and gly- a cine residues of the A46PR9, A46FR1, v Q"coE, 0-4co- o0o co aco 0 3 and A46FR2 peptides occupy the same * position, in each case replacing the glu- ° tamic acid residue of the A46 peptide evN _ q (Fig. 1). Examination of the A23FR1, A23FR2, oa)O and A28FR1 chymotryptic peptides cor- E ID s, W.0 0 responding to the chymotryptic peptide ct "am*0 altered in mutant A23: Peptide TP3C1 S.0 is present in chymotryptic digests of the -- Cq-q -4 - a) A protein and thus can be isolated with- 0Eq Go<- out prior digestion of the protein with CD trypsin. This peptide was isolated from B C Cq-4 M -- - chymotryptic digests of the A proteins of '50 0 3 the three full revertants derived from 0 °,t. strains A23 and A28. The results of the 0 *~~0a)~~~ 0 'v-C)~ a) amino acid analyses of the three peptides E Q08° C0)~ .0 Z- a are given in Table 2. In the A protein of W >b* F. Downloaded by guest on September 28, 2021 1500 GENETICS: HENNING AND YANOFSKY PROC. N. A. S. C TP3Cl C 11 2-5 6 7 8 9 -TyrjAsp-(Pro2, Ala2)-Leu-G1uNH2-Gly-Phe Gly- UGG 4 (wild type) UAG UGC -Glu- -Arg- (A46) (A23, A28) I X/IX UUG UCG UGG UGG UUC UGG -Val- -Ala- -Gly- -Gly- -Ser- -Gly- (A46PR9) (A46FR1) (A46FR2) (A23FR1) (A23FR2) (A28FR1) FIG. 1.-The amino acid substitutions at position 8 in peptide TP3Cl and the corresponding RNA coding triplets.". 20 C indicates bonds attacked by chymotrypsin. The nucleotide sequence for glutamic acid has been assigned arbitrarily. The other sequences are based on the assumption that each mutational change involves a single nucleotide substitution. Partial amino acid se- quence data is based on unpublished studies of Carlton and Yanofsky. strains A23FR1 and A28FR1 the arginine residue characteristic of the A23 or A28 peptides is replaced by a glycine residue, while the arginine is replaced by serine in the peptide obtained from the protein of A23FR2.
Load more

Recommended publications
  • Amino Acid Recognition by Aminoacyl-Trna Synthetases
    www.nature.com/scientificreports OPEN The structural basis of the genetic code: amino acid recognition by aminoacyl‑tRNA synthetases Florian Kaiser1,2,4*, Sarah Krautwurst3,4, Sebastian Salentin1, V. Joachim Haupt1,2, Christoph Leberecht3, Sebastian Bittrich3, Dirk Labudde3 & Michael Schroeder1 Storage and directed transfer of information is the key requirement for the development of life. Yet any information stored on our genes is useless without its correct interpretation. The genetic code defnes the rule set to decode this information. Aminoacyl-tRNA synthetases are at the heart of this process. We extensively characterize how these enzymes distinguish all natural amino acids based on the computational analysis of crystallographic structure data. The results of this meta-analysis show that the correct read-out of genetic information is a delicate interplay between the composition of the binding site, non-covalent interactions, error correction mechanisms, and steric efects. One of the most profound open questions in biology is how the genetic code was established. While proteins are encoded by nucleic acid blueprints, decoding this information in turn requires proteins. Te emergence of this self-referencing system poses a chicken-or-egg dilemma and its origin is still heavily debated 1,2. Aminoacyl-tRNA synthetases (aaRSs) implement the correct assignment of amino acids to their codons and are thus inherently connected to the emergence of genetic coding. Tese enzymes link tRNA molecules with their amino acid cargo and are consequently vital for protein biosynthesis. Beside the correct recognition of tRNA features3, highly specifc non-covalent interactions in the binding sites of aaRSs are required to correctly detect the designated amino acid4–7 and to prevent errors in biosynthesis5,8.
    [Show full text]
  • Targeting Glycine Reuptake in Alcohol Seeking and Relapse
    JPET Fast Forward. Published on January 24, 2018 as DOI: 10.1124/jpet.117.244822 This article has not been copyedited and formatted. The final version may differ from this version. TITLE PAGE Targeting Glycine Reuptake in Alcohol Seeking and Relapse Valentina Vengeliene, Martin Roßmanith, Tatiane T. Takahashi, Daniela Alberati, Berthold Behl, Anton Bespalov, Rainer Spanagel Downloaded from The primary laboratory of origin: Institute of Psychopharmacology, Central Institute of jpet.aspetjournals.org Mental Health, Faculty of Medicine Mannheim, Heidelberg University, Germany; at ASPET Journals on September 30, 2021 VV, MR, TTT, RS: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, Heidelberg University, Germany; DA: Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, CH-4070 Basel, Switzerland; BB, AB: Department of Neuroscience Research, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany; AB: Department of Psychopharmacology, Pavlov Medical University, St Petersburg, Russia JPET #244822 JPET Fast Forward. Published on January 24, 2018 as DOI: 10.1124/jpet.117.244822 This article has not been copyedited and formatted. The final version may differ from this version. RUNNING TITLE GlyT1 in Alcohol Seeking and Relapse Corresponding author with complete address: Valentina Vengeliene, Institute of Psychopharmacology, Central Institute of Mental Health (CIMH), J5, 68159 Mannheim, Germany Email: [email protected], phone: +49-621-17036261; fax: +49-621- Downloaded from 17036255 jpet.aspetjournals.org The number of text pages: 33 Number of tables: 0 Number of figures: 6 Number of references: 44 at ASPET Journals on September 30, 2021 Number of words in the Abstract: 153 Number of words in the Introduction: 729 Number of words in the Discussion: 999 A recommended section assignment to guide the listing in the table of content: Drug Discovery and Translational Medicine 2 JPET #244822 JPET Fast Forward.
    [Show full text]
  • A Review of Dietary (Phyto)Nutrients for Glutathione Support
    nutrients Review A Review of Dietary (Phyto)Nutrients for Glutathione Support Deanna M. Minich 1,* and Benjamin I. Brown 2 1 Human Nutrition and Functional Medicine Graduate Program, University of Western States, 2900 NE 132nd Ave, Portland, OR 97230, USA 2 BCNH College of Nutrition and Health, 116–118 Finchley Road, London NW3 5HT, UK * Correspondence: [email protected] Received: 8 July 2019; Accepted: 23 August 2019; Published: 3 September 2019 Abstract: Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.
    [Show full text]
  • Amino Acid Chemistry
    Handout 4 Amino Acid and Protein Chemistry ANSC 619 PHYSIOLOGICAL CHEMISTRY OF LIVESTOCK SPECIES Amino Acid Chemistry I. Chemistry of amino acids A. General amino acid structure + HN3- 1. All amino acids are carboxylic acids, i.e., they have a –COOH group at the #1 carbon. 2. All amino acids contain an amino group at the #2 carbon (may amino acids have a second amino group). 3. All amino acids are zwitterions – they contain both positive and negative charges at physiological pH. II. Essential and nonessential amino acids A. Nonessential amino acids: can make the carbon skeleton 1. From glycolysis. 2. From the TCA cycle. B. Nonessential if it can be made from an essential amino acid. 1. Amino acid "sparing". 2. May still be essential under some conditions. C. Essential amino acids 1. Branched chain amino acids (isoleucine, leucine and valine) 2. Lysine 3. Methionine 4. Phenyalanine 5. Threonine 6. Tryptophan 1 Handout 4 Amino Acid and Protein Chemistry D. Essential during rapid growth or for optimal health 1. Arginine 2. Histidine E. Nonessential amino acids 1. Alanine (from pyruvate) 2. Aspartate, asparagine (from oxaloacetate) 3. Cysteine (from serine and methionine) 4. Glutamate, glutamine (from α-ketoglutarate) 5. Glycine (from serine) 6. Proline (from glutamate) 7. Serine (from 3-phosphoglycerate) 8. Tyrosine (from phenylalanine) E. Nonessential and not required for protein synthesis 1. Hydroxyproline (made postranslationally from proline) 2. Hydroxylysine (made postranslationally from lysine) III. Acidic, basic, polar, and hydrophobic amino acids A. Acidic amino acids: amino acids that can donate a hydrogen ion (proton) and thereby decrease pH in an aqueous solution 1.
    [Show full text]
  • L -Glutamic Acid (G1251)
    L-Glutamic acid Product Number G 1251 Store at Room Temperature Product Description Precautions and Disclaimer Molecular Formula: C5H9NO4 For Laboratory Use Only. Not for drug, household or Molecular Weight: 147.1 other uses. CAS Number: 56-86-0 pI: 3.081 Preparation Instructions 1 pKa: 2.10 (α-COOH), 9.47 (α-NH2), 4.07 (ϕ-COOH) This product is soluble in 1 M HCl (100 mg/ml), with 2 Specific Rotation: D +31.4 ° (6 N HCl, 22.4 °C) heat as needed, yielding a clear, colorless solution. Synonyms: (S)-2-aminoglutaric acid, (S)-2- The solubility in water at 25 °C has been reported to aminopentanedioic acid, 1-aminopropane-1,3- be 8.6 mg/ml.2 dicarboxylic acid, Glu2 Storage/Stability L-Glutamic acid is one of the two amino acids that Aqueous glutamic acid solutions will form contains a carboxylic acid group in its side chains. pyrrolidonecarboxylic acid slowly at room temperature Glutamic acid is commonly referred to as "glutamate", and more rapidly at 100 °C.9 because its carboxylic acid side chain will be deprotonated and thus negatively charged in its References anionic form at physiological pH. In amino acid 1. Molecular Biology LabFax, Brown, T. A., ed., BIOS metabolism, glutamate is formed from the transfer of Scientific Publishers Ltd. (Oxford, UK: 1991), p. amino groups from amino acids to α-ketoglutarate. It 29. thus acts as an intermediary between ammonia and 2. The Merck Index, 12th ed., Entry# 4477. the amino acids in vivo. Glutamate is converted to 3. Biochemistry, 3rd ed., Stryer, L., W.
    [Show full text]
  • COVID-19: the Disease, the Immunological Challenges, the Treatment with Pharmaceuticals and Low-Dose Ionizing Radiation
    cells Review COVID-19: The Disease, the Immunological Challenges, the Treatment with Pharmaceuticals and Low-Dose Ionizing Radiation Jihang Yu 1 , Edouard I. Azzam 1, Ashok B. Jadhav 1 and Yi Wang 1,2,* 1 Radiobiology and Health, Isotopes, Radiobiology & Environment Directorate (IRED), Canadian Nuclear Laboratories (CNL), Chalk River, ON K0J 1J0, Canada; [email protected] (J.Y.); [email protected] (E.I.A.); [email protected] (A.B.J.) 2 Department of Biochemistry Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada * Correspondence: [email protected]; Tel.: +1-613-584-3311 (ext. 42653) Abstract: The year 2020 will be carved in the history books—with the proliferation of COVID-19 over the globe and with frontline health workers and basic scientists worldwide diligently fighting to alleviate life-threatening symptoms and curb the spread of the disease. Behind the shocking prevalence of death are countless families who lost loved ones. To these families and to humanity as a whole, the tallies are not irrelevant digits, but a motivation to develop effective strategies to save lives. However, at the onset of the pandemic, not many therapeutic choices were available besides supportive oxygen, anti-inflammatory dexamethasone, and antiviral remdesivir. Low-dose radiation (LDR), at a much lower dosage than applied in cancer treatment, re-emerged after a Citation: Yu, J.; Azzam, E.I.; Jadhav, 75-year silence in its use in unresolved pneumonia, as a scientific interest with surprising effects in A.B.; Wang, Y. COVID-19: The soothing the cytokine storm and other symptoms in severe COVID-19 patients.
    [Show full text]
  • Solutions to 7.012 Problem Set 1
    MIT Biology Department 7.012: Introductory Biology - Fall 2004 Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette Gardel Solutions to 7.012 Problem Set 1 Question 1 Bob, a student taking 7.012, looks at a long-standing puddle outside his dorm window. Curious as to what was growing in the cloudy water, he takes a sample to his TA, Brad Student. He wanted to know whether the organisms in the sample were prokaryotic or eukaryotic. a) Give an example of a prokaryotic and a eukaryotic organism. Prokaryotic: Eukaryotic: All bacteria Yeast, fungi, any animial or plant b) Using a light microscope, how could he tell the difference between a prokaryotic organism and a eukaryotic one? The resolution of the light microscope would allow you to see if the cell had a true nucleus or organelles. A cell with a true nucleus and organelles would be eukaryotic. You could also determine size, but that may not be sufficient to establish whether a cell is prokaryotic or eukaryotic. c) What additional differences exist between prokaryotic and eukaryotic organisms? Any answer from above also fine here. In addition, prokaryotic and eukaryotic organisms differ at the DNA level. Eukaryotes have more complex genomes than prokaryotes do. Question 2 A new startup company hires you to help with their product development. Your task is to find a protein that interacts with a polysaccharide. a) You find a large protein that has a single binding site for the polysaccharide cellulose. Which amino acids might you expect to find in the binding pocket of the protein? What is the strongest type of interaction possible between these amino acids and the cellulose? Cellulose is a polymer of glucose and as such has many free hydroxyl groups.
    [Show full text]
  • Stimulation Effects of Foliar Applied Glycine and Glutamine Amino Acids
    Open Agriculture. 2019; 4: 164–172 Research Article Yaghoub Aghaye Noroozlo, Mohammad Kazem Souri*, Mojtaba Delshad Stimulation Effects of Foliar Applied Glycine and Glutamine Amino Acids on Lettuce Growth https://doi.org/10.1515/opag-2019-0016 received June 27, 2018; accepted January 20, 2019 1 Introduction Abstract: Amino acids have various roles in plant In biology, amino acids have vital roles in cell life. Amino metabolism, and exogenous application of amino acids acids are among the most important primary metabolites may have benefits and stimulation effects on plant growth within the plant cells. However, they are frequently and quality. In this study, the growth and nutrient uptake regarded as secondary metabolites, particularly in the of Romain lettuce (Lactuca sativa subvar Sahara) were case of proline, glycine and betaine amino acids. Many evaluated under spray of glycine or glutamine at different physiochemical characteristics of plant cells, tissues and concentrations of 0 (as control), 250, 500 and 1000 organs are influenced by the presence of amino acids (Rai mg.L-1, as well as a treatment of 250 mg.L-1 glycine+250 2002; Marschner 2011). They are the building units of mg.L-1 glutamine. The results showed that there was proteins, as the main component of living cells that have significant increase in leaf total chlorophyll content under vital roles in many cell metabolic reactions (Kielland 1994; Gly250+Glu250, Gly250 and Glu1000 mg.L-1treatments, and Rainbird et al. 1984; Jones and Darrah 1993). In addition, in leaf carotenoids content under 250 mg.L-1 glutamine amino acids have various important biological functions spray compared with the control plants.
    [Show full text]
  • Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors
    Neurochemical Research (2019) 44:735–750 https://doi.org/10.1007/s11064-018-02712-1 REVIEW PAPER Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors Sumit Barua1 · Jong Youl Kim1 · Jae Young Kim1 · Jae Hwan Kim4 · Jong Eun Lee1,2,3 Received: 15 October 2018 / Revised: 19 December 2018 / Accepted: 24 December 2018 / Published online: 4 January 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract The central nervous system (CNS) is the most injury-prone part of the mammalian body. Any acute or chronic, central or peripheral neurological disorder is related to abnormal biochemical and electrical signals in the brain cells. As a result, ion channels and receptors that are abundant in the nervous system and control the electrical and biochemical environment of the CNS play a vital role in neurological disease. The N-methyl-D-aspartate receptor, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor, kainate receptor, acetylcholine receptor, serotonin receptor, α2-adrenoreceptor, and acid-sensing ion channels are among the major channels and receptors known to be key components of pathophysiological events in the CNS. The primary amine agmatine, a neuromodulator synthesized in the brain by decarboxylation of L-arginine, can regu- late ion channel cascades and receptors that are related to the major CNS disorders. In our previous studies, we established that agmatine was related to the regulation of cell differentiation, nitric oxide synthesis, and murine brain endothelial cell migration, relief of chronic pain, cerebral edema, and apoptotic cell death in experimental CNS disorders.
    [Show full text]
  • Flavor Masking/Enhancement
    T,&YJJIVMRK %RMQEP*IIHW *PEZSV1EWOMRK)RLERGIQIRX 'LIQMGEP-RXIVQIHMEXI ® §%7MQTPI%QMRS%GMH [MXL'SQTPI\*YRGXMSREPMX] Glycine, also known as aminoacetic acid, is the simplest amino acid. Found naturally in many foods, glycine is also synthesized in the human body, where, among other functions, it helps improve glycogen storage, is utilized in the synthesis of hemoglobin, collagen, and glutathione, and facilitates the amelioration of high blood fat and uric acid levels. In addition to the important metabolic functions glycine &YJJIVMRKT,7XEFMPM^EXMSR performs, this versatile substance is widely used in With acidic and basic properties in the same molecule, a range of applications, such as flavor enhancers and glycine acts to buffer or stabilize the pH of those maskers, pH buffers and stabilizers, ingredients in phar- systems containing it. Many of the uses for glycine maceutical products, and as a chemical intermediate. depend on this ability. Glycine’s efficiency in stabilizing pH has resulted in %X,SQIMRE,SWXSJ%TTPMGEXMSRW its wide usage as a buffering agent in many pharma- ceutical products. Antacid and analgesic products are often formulated with glycine to stabilize the acidity *PEZSV1EWOMRK*PEZSV)RLERGIQIRX of the digestive tract and prevent hyperacidity. Glycine Glycine has a refreshingly sweet taste, and is one and a has been shown to promote the gastric absorption of half times as sweet as sugar. In addition to its sweetness, certain drugs, including aspirin. glycine also has the ability to mellow saltiness and bit- terness. The bitter after-taste of saccharin, for example, When formulated in an aluminum-zirconium is masked by glycine. Carbonated soft drinks and flavor tetrachlorohydrex complex, glycine buffers the high concentrates based on saccharin may contain up to 0.2 acidity of active ingredients in antiperspirants.
    [Show full text]
  • Toluene Toxicity
    Case Studies in Environmental Medicine Course: SS3061 Date: February 2001 Original Date: August 1993 Expiration Date: February 28, 2007 TOLUENE TOXICITY Environmental Alert Use of toluene is increasing, in part because of its popularity as a solvent replacement for benzene. Gasoline contains 5% to 7% toluene by weight, making toluene a common airborne contaminant in industrialized countries. Many organic solvents have great addictive potential; toluene is the most commonly abused hydrocarbon solvent, primarily through “glue sniffing.” This monograph is one in a series of self- instructional publications designed to increase the primary care provider’s knowledge of hazardous substances in the environment and to aid in the evaluation of potentially exposed patients. This course is also available on the ATSDR Web site, www.atsdr.cdc.gov/HEC/CSEM/. See page 3 for more information about continuing medical education credits, continuing nursing education units, and continuing education units. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Agency for Toxic Substances and Disease Registry Division of Toxicology and Environmental Medicine Toluene Toxicity Table of Contents ATSDR/DHEP Authors: Kim Gehle, MD, MPH; Felicia Pharagood-Wade, MD; Darlene Case Study ......................................................................................... 5 Johnson, RN, BSN, MA; Lourdes Who’s At Risk .................................................................................... 5 Rosales-Guevara, MD ATSDR/DHEP Revision Planners: Exposure Pathways ...........................................................................
    [Show full text]
  • Nucleotide Base Coding and Am1ino Acid Replacemients in Proteins* by Emil L
    VOL. 48, 1962 BIOCHEMISTRY: E. L. SAIITH 677 18 Britten, R. J., and R. B. Roberts, Science, 131, 32 (1960). '9 Crestfield, A. M., K. C. Smith, and F. WV. Allen, J. Biol. Chem., 216, 185 (1955). 20 Gamow, G., Nature, 173, 318 (1954). 21 Brenner, S., these PROCEEDINGS, 43, 687 (1957). 22 Nirenberg, M. WV., J. H. Matthaei, and 0. WV. Jones, unpublished data. 23 Crick, F. H. C., L. Barnett, S. Brenner, and R. J. Watts-Tobin, Nature, 192, 1227 (1961). 24 Levene, P. A., and R. S. Tipson, J. Biol. Ch-nn., 111, 313 (1935). 25 Gierer, A., and K. W. Mundry, Nature, 182, 1437 (1958). 2' Tsugita, A., and H. Fraenkel-Conrat, J. Mllot. Biol., in press. 27 Tsugita, A., and H. Fraenkel-Conrat, personal communication. 28 Wittmann, H. G., Naturwissenschaften, 48, 729 (1961). 29 Freese, E., in Structure and Function of Genetic Elements, Brookhaven Symposia in Biology, no. 12 (1959), p. 63. NUCLEOTIDE BASE CODING AND AM1INO ACID REPLACEMIENTS IN PROTEINS* BY EMIL L. SMITHt LABORATORY FOR STUDY OF HEREDITARY AND METABOLIC DISORDERS AND THE DEPARTMENTS OF BIOLOGICAL CHEMISTRY AND MEDICINE, UNIVERSITY OF UTAH COLLEGE OF MEDICINE Communicated by Severo Ochoa, February 14, 1962 The problem of which bases of messenger or template RNA' specify the coding of amino acids in proteins has been largely elucidated by the use of synthetic polyri- bonucleotides.2-7 For these triplet nucleotide compositions (Table 1), it is of in- terest to examine some of the presently known cases of amino acid substitutions in polypeptides or proteins of known structure.
    [Show full text]