DOCSLIB.ORG

Isoleucine-Mediated Regulation of Genome Replication in Various Mammalian Cell Lines1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Isoleucine-Mediated Regulation of Genome Replication in Various Mammalian Cell Lines1 [CANCER RESEARCH 31, 46—51, January 1971] Isoleucine-mediated Regulation of Genome Replication in Various Mammalian Cell Lines1 R. A. Tobey and K. D. Ley2 Biomedical ResearchGroup, Los Alamos Scientific Laboratory, University of California, Los Alamos, New Mexico 87544 SUMMARY medium (1 5). In the absence of sufficient quantities of isoleucine and glutamine, the cells initially in S, G@, and M When suspension cultures of Chinese hamster cells (line continued traverse of the cell cycle and accumulated in @, CHO) are grown in isoleucine-deficient F-l0 medium but cells in G1 were unable to initiate DNA synthesis and supplemented with dialyzed sera, the entire population of cells resume cell-cycle traverse in synchrony. Deliberate omission of @ accumulates in a state of arrest within 24 to 36 hr. Merely other amino acids from the F-l0 medium resulted in a random by the adding back of isoleucine, the entire population distribution of cells throughout the cell cycle ( 15). It was initiates DNA synthesis and subsequently divides in suggested, therefore, that isoleucine and glutamine played a synchrony. This phenomenon is not readily observed in cells role in regulation of CHO cell genome replication. It was also infected with pleuropneumonia-like organisms . Cultures of shown that resuspension of exponentially growing cells in mouse L and Syrian hamster BHK2 1 cells also accumulate in medium deficient in both isoleucine and glutamine provided a @ G1 under conditions in which isoleucine is specifically rapid and convenient means of producing cells in arrest depleted from the culture medium, and, upon addition of without the attendant risk of partial exhaustion of other @ isoleucine, synthesis of DNA and resumption of cell-cycle nutrients that occurs during arrest in high-density cultures. traverse commence in synchrony. These results suggest that In this report, we present evidence indicating that a isoleucine-mediated regulation of genome replication may be a reversible state of G1 arrest in cultures of Chinese hamster generalized phenomenon in mammalian cells. Speculations are cells may be rapidly produced by merely removing isoleucine presented regarding possible roles for isoleucine (or its from the medium. Further evidence is provided to derivatives) in initiation of genome replication. demonstrate that this isoleucine-mediated regulation of genome replication can be demonstrated in cell lines of Syrian INTRODUCTION hamster and mouse origin as well, provided that isoleucine is specifically depleted from the culture medium and the cells are For facilitation of the study of mechanisms regulating not infected with PPLO.3 mammalian genome replication, it is essential to provide large quantities of cells under conditions in which the entire population can be induced to initiate DNA synthesis in MATERIALS AND METHODS synchrony. We had previously described a system of this type in which Chinese hamster cells (line CHO) accumulated in G1 A hypodiploid (modal chromosome number of 21) line of in suspension cultures that were grown to high cell densities in Chinese hamster cells (line CHO) was grown in F-10 medium F-b medium (21). Evidence that the cells were in G1 was supplemented with 10% calf and 5% fetal calf sera, penicillin, provided by (a) autoradiographic studies, which indicated that and streptomycin. The original F-b formulation (9) has been these stationary phase cells did not incorporate labeled modified in this laboratory by omitting FeSO4 , CuSO4, thymidine into DNA; (b) microfluorometric measurements, ZnSO4 , CaC12, and sodium pyruvate. Syrian hamster @ which indicated that the arrested cells contained the BHK21/Cl3 cells were obtained from Dr. Alexander Kisch and complement of DNA; and (c) data which signified that, in were grown in F-b medium. Mouse L-929 cells were grown in cultures resuspended in fresh medium, DNA synthesis always minimum essential medium (Grand Island Biological Co., preceded cell division (21). Reversal of G1 arrest was Grand Island, N. Y.) supplemented with 10% fetal calf serum, accomplished by resuspending the cells in fresh medium, penicillin, and streptomycin. In certain experiments, cells were which stimulated the cells to initiate DNA synthesis and to grown in an isoleucine-deficient medium. The media used were divide in synchrony. identical in composition to those described above except that @ Further studies indicated that accumulation in resulted they contained no isoleucine and were supplemented with from a depletion of isoleucine and glutamine from the culture dialyzed sera. The sera (10% calf and 5% fetal calf) were dialyzed against Earle's balanced salt solution, pH 7.2, at a 1 This work was performed under the auspices of the U. S. Atomic 1:10 volume for 6 days at 3°,with changes of salt solution on Energy Commission. alternate days. All of the above cells were examined routinely 2 Recipient of NIH Postdoctoral Fellowship i-F02-CA43809-01 for contamination with PPLO by the method of Chanock et al. from the National Cancer Institute. Received July 10, 1970; accepted September 18, 1970. 3The abbreviation used is: PPLO, pleuropneumonia-like organism. 46 CANCER RESEARCH VOL. 31 Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1971 American Association for Cancer Research. Isoleucine Regulation of Genome Replication (1), with the modified technique of House and Waddell (12) for preparation of yeast extract. No PPLO were detected in any of these lines during the course of these experiments. A culture of CHO cells was deliberately infected with the PPLO Mycoplasma hyorhinis (kindly provided by Dr. Elliot Levine). This culture (designated PPLO-CHO) became persistently infected and, whenever plated on the agar z described above, gave rise to PPLO colonies. 0 Cell concentrations were determined in monodisperse C) populations of CHO and L-cells to a precision of 1% or better 4 with an electronic particle counter, as described previously 0 w (19). The fraction of cells incorporating thymidine-methyl-3 H 0 > (6 Ci/mmole,SchwarzBioResearch,Inc.,Orangeburg,N.Y.) 0 was measured autoradiographically and scored as described previously (21). 0 0 ‘U -I RESULTS For conclusive demonstration of the primary role of isoleucine in reversibly inducing a state of G1 arrest, it is necessary to provide evidence for the pheomenon in cultures maintained in medium singly deficient in isoleucine. Consequently, CHO cells from an exponentially growing culture were washed and resuspended in isoleucine-deficient F-lO medium containing twice the normal concentration of glutamine to prevent glutamine from becoming depleted, HOURS supplemented with dialyzed serum, in a spinner flask. As was Chart 1. Reversal of G1 arrest in cultures of CHO cells maintained shown elsewhere (1 5), there was an immediate reduction in in isoleucine-deficient F-i0 medium. Cultures were grown for 48 hr rate of division, with the cell number increasing by 33% (the in isoleucine-deficient medium containing 2 times the normal approximate number of cells initially in 5, G2 , and M) during glutamine concentration and dialyzed serum, then, at t 0, cells were the first 18 hr after transfer to isoleucine-deficient medium; resuspended in fresh complete medium (A), or to the cultures in thereafter, the cell concentration remained constant, and the deficient medium were added back either 2 times the normal fraction of cells incorporating thymidine-3 H into DNA concentration of isoleucine and glutamine (B) or 2 times the normal dropped essentially to 0. Upon resuspension of these cells in isoleucine concentration only (C). Thymidine-methyl-3 H was added to all cultures at t = 0 to a final concentration of 0.05 zCi/ml, and fresh complete medium (Chart 1A) or after addition to the samples were removed at intervals for autoradiographic determination isoleucine-deficient cultures of either isoleucine and glutamine of the labeled fraction. In this and subsequent charts, labeled or (Chart lB) or isoleucine only (Chart lC), the entire population divided fraction represents N/N0 —1. •, fraction labeled with of cells first initiated DNA synthesis (measured by thymidine-3 H; 0, the divided fraction. autoradiographic determination of the fraction of cells labeled with thymidine-3 H, the label being added at t 0) and then contamination on isoleucine-specific synchrony induction was divided in synchrony. In this and later figures, “labeledor determined by growing infected cells to high density in divided fraction― represents N/N0 —1. The rate at which the complete medium or by resuspending PPLO-CHO cells in cells entered S and subsequently divided is essentially the same isoleucine-deficient medium supplemented with dialyzed serum in all 3 cultures in Chart 1. The time course and rates of entry (Chart 2A). Also shown in Chart 2A is a noninfected control into S and mitosis in Chart 1 are comparable to values culture grown to high density in complete medium. The obtained in suspension cultures of CHO cells prepared by growth pattern of infected cells in isoleucine-deficient medium mitotic selection, in which it is known that the initial was similar to that observed in noninfected cultures in population occupied less than 1% of the total cell cycle (5, 6, complete medium (1 5), but the infected cells grown in 18, 20, 22) or an initial Engelberg (4) synchrony index of complete medium exhibited 2 grossly different properties 0.97. These results clearly indicate that, in suspension cultures from their noninfected counterparts. The maximum cell of CHO cells, it is possible to arrest cells in G1 and then to concentration in the infected culture was only slightly more induce initiation of genome replication merely by the sole than half that observed in the uninfected culture, and the addition of isoleucine in the medium. PPLO-CHO cells survived much shorter periods in stationary In view of the high incidence of contamination of common phase. Coincident with the fall in cell count was a cell lines with PPLO and documented evidence for proportionate increase in number of cells permeable to trypan competition between cells and PPLO for nutrients [for a blue, which indicates cell death.
Load more

Recommended publications
  • Effect of Peptide Histidine Isoleucine on Water and Electrolyte Transport in the Human Jejunum
    Gut: first published as 10.1136/gut.25.6.624 on 1 June 1984. Downloaded from Gut, 1984, 25, 624-628 Alimentary tract and pancreas Effect of peptide histidine isoleucine on water and electrolyte transport in the human jejunum K J MORIARTY, J E HEGARTY, K TATEMOTO, V MUTT, N D CHRISTOFIDES, S R BLOOM, AND J R WOOD From the Department of Gastroenterology, St Bartholomew's Hospital, London, The Liver Unit, King's College Hospital, London, Department ofMedicine, Hammersmith Hospital, London, and Department of Biochemistry, Karolinska Institute, Stockholm, Sweden SUMMARY Peptide histidine isoleucine, a 27 amino acid peptide with close amino acid sequence homology to vasoactive intestinal peptide and secretin, is distributed throughout the mammalian intestinal tract, where it has been localised to intramural neurones. An intestinal perfusion technique has been used to study the effect of intravenous peptide histidine isoleucine (44.5 pmol/kg/min) on water and electrolyte transport from a plasma like electrolyte solution in human jejunum in vivo. Peptide histidine isoleucine infusion produced peak plasma peptide histidine isoleucine concentrations in the range 2000-3000 pmolIl, flushing, tachycardia and a reduction in diastolic blood pressure. Peptide histidine isoleucine caused a significant inhibition of net absorption of water, sodium, potassium and bicarbonate and induced a net secretion of chloride, these changes being completely reversed during the post-peptide histidine isoleucine period. These findings suggest that endogenous peptide histidine isoleucine may participate in the neurohumoral regulation of water and electrolyte transport in the human jejunum. http://gut.bmj.com/ Peptide histidine isoleucine, isolated originally from INTESTINAL PERFUSION mammalian small intestine, is a 27-amino acid After an eight hour fast, each subject swallowed a peptide having close amino acid sequence homology double lumen intestinal perfusion tube, incorpo- to vasoactive intestinal peptide and secretin.
    [Show full text]
  • Workshop 1 – Biochemistry (Chem 160)
    Workshop 1 – Biochemistry (Chem 160) 1. Draw the following peptide at pH = 7 and make sure to include the overall charge, label the N- and C-terminus, the peptide bond and the -carbon. AVDKY Give the overall charge of the peptide at pH = 3 and 12. 2. Draw a titration curve for Arg, make sure to label the different points. Determine the pI for Arg. 3. Nonpolar solute + water = solution a. What is the S of the universe, system and surroundings? The S of the universe would decrease this is why it is not spontaneous, the S of the system would increase but to a lesser extent to which the S of the surrounding would decrease S universe = S system + S surroundings 4. What is the hydrophobic effect and explain why it is thermodynamically favorable. The hydrophobic effect is when hydrophobic molecules tend to clump together burying them and placing hydrophilic molecules on the outside. The reason this is thermodynamically favorable is because it frees caged water molecules when burying clumping the hydrophobic molecules together. 5. Urea dissolves very readily in water, but the solution becomes very cold as the urea dissolves. How is this possible? Urea dissolves in water because when dissolving there is a net increase in entropy of the universe. The heat exchange, getting colder only reflects the enthalpy (H) component of the total energy change. The entropy change is high enough to offset the enthalpy component and to add up to an overall -G 6. A mutation that changes an alanine residue in the interior of a protein to valine is found to lead to a loss of activity.
    [Show full text]
  • Amino Acids Amino Acids
    Amino Acids Amino Acids What Are Amino Acids? Essential Amino Acids Non Essential Amino Acids Amino acids are the building blocks of proteins; proteins are made of amino acids. Isoleucine Arginine (conditional) When you ingest a protein your body breaks it down into the individual aminos, Leucine Glutamine (conditional) reorders them, re-folds them, and turns them into whatever is needed by the body at Lysine Tyrosine (conditional) that time. From only 20 amino acids, the body is able to make thousands of unique proteins with different functions. Methionine Cysteine (conditional) Phenylalanine Glycine (conditional) Threonine Proline (conditional) Did You Know? Tryptophan Serine (conditional) Valine Ornithine (conditional) There are 20 different types of amino acids that can be combined to make a protein. Each protein consists of 50 to 2,000 amino acids that are connected together in a specific Histidine* Alanine sequence. The sequence of the amino acids determines each protein’s unique structure Asparagine and its specific function in the body. Asparate Popular Amino Acid Supplements How Do They Benefit Our Health? Acetyl L- Carnitine: As part of its role in supporting L-Lysine: L-Lysine, an essential amino acid, is mental function, Acetyl L-Carnitine may help needed to support proper growth and bone Proteins (amino acids) are needed by your body to maintain muscles, bones, blood, as support memory, attention span and mental development. It can also support immune function. well as create enzymes, neurotransmitters and antibodies, as well as transport and performance. store molecules. N-Acetyl Cysteine: N-Acetyl Cysteine (NAC) is a L-Arginine: L-Arginine is a nonessential amino acid form of the amino acid cysteine.
    [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]
  • Valine and Isoleucine: the Next Limiting Amino Acids in Broiler Diets Vol
    Valine and Isoleucine: The next limiting amino acids in broiler diets Vol. 46 (1), April 2011, Page 59 Valine and Isoleucine: The next limiting amino acids in broiler diets Etienne Corrent (Ajinomoto Eurolysine S.A.S.) and Dr. Jörg Bartelt (Lohmann Animal Health GmbH & Co. KG) Drastic genetic changes have occurred in many commercial broiler lines during the last years with regard to performance. This genetic improvement needs a corresponding adjustment of our knowledge about amino acid nutrition in broilers. Additionally, today broiler feed formulators are not only focused on minimising the costs. They also have to take into consideration environmental issues and the impact of feed on broiler health. Reducing excess dietary crude protein (CP) is an important way of addressing these issues. The least cost formulation of the diet according to the ideal protein concept is the best way to supply an economic and a balanced amino acids feed for broiler, which can help to reduce the nitrogen excretion during the rearing period. What are the next limiting amino acids in broiler diets? To reduce dietary crude protein levels in broiler feed, it is necessary to know which indispensable amino acids become limiting in diets and what the requirement of broilers is. The usage of feed use amino acids (methionine sources, L-Lysine sources, L-Threonine) in broiler feed is well established. Depending on the requirement assumed for each amino acid, Valine, Isoleucine, Tryptophan and Arginine are generally considered as the next limiting amino acids in broiler feed. Indeed, the amino acid composition of protein differs between feedstuffs and can impact the order in which amino acids become limiting in diets.
    [Show full text]
  • Inhibition of Glycine Oxidation in Cultured Fibroblasts by Isoleucine
    Pediat. Res. 7: 945-947 (1973) Glycine isoleucine hyperglycemia Inhibition of Glycine Oxidation in Cultured Fibroblasts by Isoleucine RICHARD E. HILLMAN, [1S1 LUCILLE H. SOWERS, AND JACK L. COHEN Division of Medical Genetics, Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri USA Extract Cultured fibroblasts were shown to oxidize glycine to CO2- Isoleucine (10 HIM) in- hibited glycine oxidation to CO2 by about 60% in a concentration range of from 0.025 to 10 mM glycine in fibroblasts grown from a patient with ^-ketothiolase defi- cienty. Glycine oxidation by control cell lines was not inhibited by isoleucine. These studies demonstrate an interrelation between isoleucine catabolism and glycine oxida- tion in fibroblasts cultured from a patient with the ketotic hyperglycinemia syndrome. Speculation Hyperglycinemia and hyperglycinuria seen in the "ketotic hyperglycinemia" syn- drome would appear to be secondary to accumulation of products of isoleucine catabolism. Thus, the varying levels of glycine reported in the serum and urine of these patients probably reflect differences in protein and isoleucine intake than rather primary blocks in glycine metabolism. Introduction deficiency [6], methylmalonyl-CoA mutase deficiency [8], and /?-ketothiolase deficiency [3]. a-Methyl-/3-hy- Since its original description by Childs et at. [2], the droxybutyrate was found in the patient with /?-keto- "ketotic hyperglycinemia" syndrome has been shown thiolase deficiency [3]. to be associated with three different defects in the pathway from isoleucine to succinyl-CoA. The sister of There has never been a satisfactory explanation of Childs' original patient was demonstrated to have pro- the elevated levels of glycine in serum and urine of pionyl-CoA carboxylase deficiency [4], other cases have patients with these disorders of isoleucine metabolism.
    [Show full text]
  • Amino Acid Requirements of the Free-Living Nematode Caenorhabditis Briggsae
    AMINO ACID REQUIREMENTS OF THE FREE-LIVING NEMATODE CAENORHABDITIS BRIGGSAE BY J. R. VANFLETEREN Instituut voor Dierkunde, Laboratoria voor Morfologie en Systematiek, RijksuniversiteitGent, Belgium Washed yeast ribosomes promote growth and reproduction of C. briggsae, even when supple- mented to the basal medium at dosages too low to provide the organisms with sufficient amounts of essential amino acids. Hence, a re-investigation of the amino acid requirements of C. briggsae by single and multiple omission of amino acids from the basal medium revealed unambiguously that arginine, histidine, lysine, tryptophan, phenylalanine, methionine, threonine, leucine, isoleucine and valine are not synthetized at levels to permit reproduction; they are called essential amino acids. The requirement for arginine and isoleucinehowever appears to be less clear-cut. On the contrary, evidence is presented that alanine, asparagine, cysteine, glutamate, glutamine, glycine, proline, serine and tryosine can be synthetized at adequate levels; they are called non- essential amino acids. In addition it was shown that multiple omission of the non-essential amino acids is not deleterious. This is believed to be an important step towards the development of a minimum essential medium (MEM) for growth and reproduction of C. briggsae. Sustained growth of the free-living nematode Caenorhabditis brigg.rae can be obtained on a chemically defined medium, supplemented with adequate levels of a proteinaceous growth factor. The most satisfactory, chemically defined medium hitherto reported (Buecher, Hansen & Yarwood, 1966), has been called C. brigg.iae Maintenance Medium (CbMM) and is now commercially available. CbMM is an extremely rich medium, being composed of 53 components, all present at high concentrations.
    [Show full text]
  • Safety Assessment of Α-Amino Acids As Used in Cosmetics
    Safety Assessment of α-Amino Acids as Used in Cosmetics Status: Final Report for Public Distribution Release Date: October 5, 2012 Panel Meeting Date: September 10-11, 2012 The 2012 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A. Hill, Ph.D. James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is F. Alan Andersen, Ph.D. This safety assessment was prepared by Christina L. Burnett, Scientific Analyst/Writer, and Bart Heldreth, Ph.D., Chemist CIR. © Cosmetic Ingredient Review 1101 17th Street, NW, Suite 412 Washington, DC 20036-4702 ph 202.331.0651 fax 202.331.0088 [email protected] 1 ABSTRACT The Cosmetic Ingredient Review Expert Panel (the Panel) reviewed the safety of α-amino acids, which function primarily as hair and skin conditioning agents in cosmetic products. The safety of α-amino acids as direct food additives has been well established based on extensive research through acute and chronic dietary exposures. The Panel focused its review on dermal irritation and sensitization data relevant to the use of these ingredients in topical cosmetics. The Panel concluded that α-amino acids were safe as cosmetic ingredients in the practices of use and concentration of this safety assessment. INTRODUCTION Amino acids and their salts are widely used as cosmetic ingredients, and function primarily as hair conditioning agents and skin conditioning agents (humectant and miscellaneous).
    [Show full text]
  • The Wuhan Pneumonia Outbreak: High Isoleucine and High
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 20 February 2020 doi:10.20944/preprints202002.0289.v1 The Wuhan Pneumonia outbreak: High isoleucine and high valine plus glycine contents are features of the proteins of 2019- nCoV virus Sirui Yan1, Yulin Wan1, Ying Zhang2, Shanshan An1, Kaiqiao Yang1, Huan Xu3, Qiuyun Liu1,* 1State Key Laboratory of Biocontrol, Biomedical Center, Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China. 2Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. 3School of Electronic Information and Automation, Guilin University of Aerospace Technology, Guilin 541004, Guangxi, China. Sirui Yan and Yulin Wan made equal contributions to this work. *Corresponding author: Qiuyun Liu, Ph.D, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China. Tel: +86 (020)84110296; E-mail: [email protected] © 2020 by the author(s). Distributed under a Creative Commons CC BY license. Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 20 February 2020 doi:10.20944/preprints202002.0289.v1 Abstract The current pneumonia epidemic in China could evolve into a pandemic on a global scale if not effectively contained. The 2019-nCoV possesses a 61-amino acid open reading frame resembling SARS-CoV virulence factor - ORF6 peptide. The isoleucine content is 15.9% in ORF6 of SARS-CoV versus 16.4% of that in 2019-nCoV. Given the proton affinity in the carbonyl oxygen in isoleucine, augmented proton traffic can enhance proton-ion antiport and prompt cell swelling. As the content of essential amino acids in the open reading frame of 2019-nCoV reaches 57.4%, a starch/vitamin diet served for short period of time does not give rise to essential amino acids and halts virion production, which could be adopted as prophylactic approach of many viral infections.
    [Show full text]
  • Amino Acid Side Chain Conformation in Angiotensin II and Analogs
    Proc. Nati. Acad. Sci. USA Vol. 77, No. 1, pp. 82-86, January 1980 Biochemistry Amino acid side chain conformation in angiotensin II and analogs: Correlated results of circular dichroism and 1H nuclear magnetic resonance (peptide hormones/competitive inhibitor/N-methylation/pH titration) F. PIRIou*, K. LINTNER*, S. FERMANDJIAN*, P. FROMAGEOT*, M. C. KHOSLAt, R. R. SMEBYt, AND F. M. BUMPUSt *Service de Biochimie, D)partement de Biologie, Centre d'Etudes Nucl&aires de Saclay, P.B. No. 2, F-91190 Gif-sur-Yvette, France; and tThe Clinic Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44106 Communicated by Irvine H. Page, September 4,1979 ABSTRACT [1-Sarcosine,S-isoleucinelangiotensin II (Sar- [Sarl,11e8]Angiotensin II was shown to be a potent antagonist Arg-Val-Tyr-Ile-His-Pro-Ile) has been shown to be a potent an- of the pressor action of antiotensin II (Asp-Arg-Val-Tyr-Ile- tagonist of the pressor action of angiotensin II. With a view to increase half-life in vivo of this peptide, the amino acid residue His-Pro-Phe). However, this and other similar antagonistic at position 4 (tyrosine) or position 5 (isoleucine) was replaced peptides have short half-lives in vivo; the shortness is presum- with the corresponding N-methylated residue. This change ably due to rapid degradation by peptidases (for detailed re- drastically reduced the antagonistic properties of this analog. views, see refs. 1 and 2). With a view to render these peptides The present work was therefore undertaken to investigate the more resistant to enzymatic degradation, the residue at position effect of N-methylation on overall conformation of these pep- tides and to determine the conformational requirements for 4 (tyrosine) or position 5 (isoleucine) was replaced with the maximum agonistic or antagonistic pro rties.
    [Show full text]
  • Histidine: a Systematic Review on Metabolism and Physiological Effects in Human and Different Animal Species
    nutrients Review Histidine: A Systematic Review on Metabolism and Physiological Effects in Human and Different Animal Species Joanna Moro 1, Daniel Tomé 1, Philippe Schmidely 2, Tristan-Chalvon Demersay 3 and Dalila Azzout-Marniche 1,* 1 AgroParisTech, Université Paris-Saclay, INRAE, UMR PNCA, 75005 Paris, France; [email protected] (J.M.); [email protected] (D.T.) 2 AgroParisTech, Université Paris-Saclay, INRAE, UMR0791 Mosar, 75005 Paris, France; [email protected] 3 Ajinomoto Animal Nutrition Europe, 75017 Paris, France; [email protected] * Correspondence: [email protected]; Tel.: +33-1-44087244 Received: 1 April 2020; Accepted: 8 May 2020; Published: 14 May 2020 Abstract: Histidine is an essential amino acid (EAA) in mammals, fish, and poultry. We aim to give an overview of the metabolism and physiological effects of histidine in humans and different animal species through a systematic review following the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In humans, dietary histidine may be associated with factors that improve metabolic syndrome and has an effect on ion absorption. In rats, histidine supplementation increases food intake. It also provides neuroprotection at an early stage and could protect against epileptic seizures. In chickens, histidine is particularly important as a limiting factor for carnosine synthesis, which has strong anti-oxidant effects. In fish, dietary histidine may be one of the most important factors in preventing cataracts. In ruminants, histidine is a limiting factor for milk protein synthesis and could be the first limiting AA for growth. In excess, histidine supplementation can be responsible for eating and memory disorders in humans and can induce growth retardation and metabolic dysfunction in most species.
    [Show full text]
  • 24Amino Acids, Peptides, and Proteins
    WADEMC24_1153-1199hr.qxp 16-12-2008 14:15 Page 1153 CHAPTER COOϪ a -h eli AMINO ACIDS, x ϩ PEPTIDES, AND NH3 PROTEINS Proteins are the most abundant organic molecules 24-1 in animals, playing important roles in all aspects of cell structure and function. Proteins are biopolymers of Introduction 24A-amino acids, so named because the amino group is bonded to the a carbon atom, next to the carbonyl group. The physical and chemical properties of a protein are determined by its constituent amino acids. The individual amino acid subunits are joined by amide linkages called peptide bonds. Figure 24-1 shows the general structure of an a-amino acid and a protein. α carbon atom O H2N CH C OH α-amino group R side chain an α-amino acid O O O O O H2N CH C OH H2N CH C OH H2N CH C OH H2N CH C OH H2N CH C OH CH3 CH2OH H CH2SH CH(CH3)2 alanine serine glycine cysteine valine several individual amino acids peptide bonds O O O O O NH CH C NH CH C NH CH C NH CH C NH CH C CH3 CH2OH H CH2SH CH(CH3)2 a short section of a protein a FIGURE 24-1 Structure of a general protein and its constituent amino acids. The amino acids are joined by amide linkages called peptide bonds. 1153 WADEMC24_1153-1199hr.qxp 16-12-2008 14:15 Page 1154 1154 CHAPTER 24 Amino Acids, Peptides, and Proteins TABLE 24-1 Examples of Protein Functions Class of Protein Example Function of Example structural proteins collagen, keratin strengthen tendons, skin, hair, nails enzymes DNA polymerase replicates and repairs DNA transport proteins hemoglobin transports O2 to the cells contractile proteins actin, myosin cause contraction of muscles protective proteins antibodies complex with foreign proteins hormones insulin regulates glucose metabolism toxins snake venoms incapacitate prey Proteins have an amazing range of structural and catalytic properties as a result of their varying amino acid composition.
    [Show full text]