Interpretive Guide for Amino Acids
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Hydroxylation of the Eukaryotic Ribosomal Decoding Center Affects Translational Accuracy
Hydroxylation of the eukaryotic ribosomal decoding center affects translational accuracy Christoph Loenarza,1, Rok Sekirnika,2, Armin Thalhammera,2, Wei Gea, Ekaterina Spivakovskya, Mukram M. Mackeena,b,3, Michael A. McDonougha, Matthew E. Cockmanc, Benedikt M. Kesslerb, Peter J. Ratcliffec, Alexander Wolfa,4, and Christopher J. Schofielda,1 aChemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford OX1 3TA, United Kingdom; bTarget Discovery Institute, University of Oxford, Oxford OX3 7FZ, United Kingdom; and cCentre for Cellular and Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom Edited by William G. Kaelin, Jr., Harvard Medical School, Boston, MA, and approved January 24, 2014 (received for review July 31, 2013) The mechanisms by which gene expression is regulated by oxygen Enzyme-catalyzed hydroxylation of intracellularly localized are of considerable interest from basic science and therapeutic proteins was once thought to be rare, but accumulating recent perspectives. Using mass spectrometric analyses of Saccharomyces evidence suggests it is widespread (11). Motivated by these cerevisiae ribosomes, we found that the amino acid residue in findings, we investigated whether the translation of mRNA to closest proximity to the decoding center, Pro-64 of the 40S subunit protein is affected by oxygen-dependent modifications. A rapidly ribosomal protein Rps23p (RPS23 Pro-62 in humans) undergoes growing eukaryotic cell devotes most of its resources to the tran- posttranslational hydroxylation. We identify RPS23 hydroxylases scription, splicing, and transport of ribosomal proteins and rRNA as a highly conserved eukaryotic subfamily of Fe(II) and 2-oxoglu- (12). We therefore reasoned that ribosomal modification is a tarate dependent oxygenases; their catalytic domain is closely re- candidate mechanism for the regulation of protein expression. -
N-Acyl Taurines Are Endogenous Lipid Messengers That Improve Glucose Homeostasis
N-acyl taurines are endogenous lipid messengers that improve glucose homeostasis Trisha J. Grevengoeda, Samuel A. J. Trammella, Michele K. McKinneyb,c, Natalia Petersena, Rebecca L. Cardoned, Jens S. Svenningsena, Daisuke Ogasawarab,c, Christina C. Nexøe-Larsene, Filip K. Knopa,e,f,g, Thue W. Schwartza, Richard G. Kibbeyd, Benjamin F. Cravattb,c,1, and Matthew P. Gilluma,1 aNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; bDepartment of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037; cDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037; dDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06519; eCenter for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark; fDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; and gClinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte, 2820 Hellerup, Denmark Contributed by Benjamin F. Cravatt, October 17, 2019 (sent for review September 19, 2019; reviewed by George Kunos and Richard Lehner) Fatty acid amide hydrolase (FAAH) degrades 2 major classes of involvement in the endocannabinoid system may have, to date, bioactive fatty acid amides, the N-acylethanolamines (NAEs) and overshadowed the study of NATs, the physiological functions N-acyl taurines (NATs), in central and peripheral tissues. A functional of which remain poorly understood despite their bioactivity and polymorphism in the human FAAH gene is linked to obesity and dysregulation in disease states (20–22). mice lacking FAAH show altered metabolic states, but whether these NATs have been identified by liquid chromatography-tandem phenotypesarecausedbyelevationsinNAEsorNATsisunknown. -
Cloning and Expression of a Cdna Encoding the Transporter of Taurine
Proc. Natl. Acad. Sci. USA Vol. 89, pp. 12145-12149, December 1992 Biochemistry Cloning and expression of a cDNA encoding the transporter of taurine and /8-alanine in mouse brain (neurotransmitters/membrane protein/moecular cloning) QING-RONG Liu, BEATRIZ L6PEZ-CORCUERA, HANNAH NELSON, SREEKALA MANDIYAN, AND NATHAN NELSON* Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110 Communicated by Leon A. Heppel, September 8, 1992 (receivedfor review July 30, 1992) ABSTRACT A taurine/fl-alanine transporter was cloned hippocampus induced an increase in chloride permeability of from a mouse brain cDNA library by screening with a partial the cellular membranes (16, 17). Responses to all of those cDNA probe of the glycine transporter at low stringency. The substances were blocked by external strychnine, indicating deduced amino acid sequence predicts 590 amino acids with that they interacted with the same system. However, no typical characteristics of the sodium-dependent neurotrans- specific receptors for taurine or f-alanine could be identified. mitter transporters such as sequence homology and membrane Moreover, /3-alanine and taurine uptake systems could be topography. However, the calculated isoelectric point of the shared by other neurotransmitters. It was reported that a taurine/fi-alanine transporter is more acidic (pI = 5.98) than low-affinity GABA transporter accumulates taurine and those (pI > 8.0) ofother cloned neurotransmitter transporters. f3-alanine (18). The taurine transporter takes up /3-alanine Xenopus oocytes Injected with cRNA of the cloned transporter with high efficiency in neuronal and astroglial cells in culture. expressed uptake activities with K. = 4.5 FM for taurine and In this communication we report on the cloning and expres- K. -
Significance of Urinary Hydroxyproline in Man
SIGNIFICANCE OF URINARY HYDROXYPROLINE IN MAN Darwin J. Prockop, Albert Sjoerdsma J Clin Invest. 1961;40(5):843-849. https://doi.org/10.1172/JCI104318. Find the latest version: https://jci.me/104318/pdf SIGNIFICANCE OF URINARY HYDROXYPROLINE IN MAN By DARWIN J. PROCKOP AND ALBERT SJOERDSMA (From the Section of Experimental Therapeutics, National Heart Institute, Bethesda, Md.) (Submitted for publication September 27, 1960; accepted January 12, 1961) Since nearly all of the hydroxyproline of the of Marfan's syndrome (2) reflect a rapid rate of body is found in collagen, it has been suggested collagen degradation. (1, 2) that the urinary excretion of this imino An incidental discovery in the study was that acid may be an important index of collagen me- the increase in urinary hydroxyproline after in- tabolism. The origin of urinary hydroxyproline, gestion of gelatin represents an increased excre- however, is not definitely established. The iso- tion of hydroxyproline peptides. This appears to topic studies of Stetten (3) in rats indirectly sug- be the first demonstration that significant amounts gested that most of the free and peptide hydroxy- of peptides can be excreted following ingestion of proline in the body arises from the breakdown of a protein. collagen, since she found that hydroxyproline-N'5 was not significantly incorporated into collagen. MATERIALS AND METHODS Ziff, Kibrick, Dresner and Gribetz (1), on the The 8 subjects utilized in the study were hospitalized other hand, observed an increased excretion of for periods of 3 to 12 weeks; 3 were patients with Mar- hydroxyproline when it was added to the diet of fan's syndrome, 2 of whom were previously shown to have elevated excretions of hydroxyproline (2). -
Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine As Causal Trait for Type 2 Diabetes
nutrients Article Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes Susanne Jäger 1,2,* , Rafael Cuadrat 1,2, Clemens Wittenbecher 1,2,3, Anna Floegel 4, Per Hoffmann 5,6, Cornelia Prehn 7 , Jerzy Adamski 2,7,8,9 , Tobias Pischon 10,11,12 and Matthias B. Schulze 1,2,13 1 Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany; [email protected] (R.C.); [email protected] (C.W.); [email protected] (M.B.S.) 2 German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; [email protected] 3 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA 4 Leibniz Institute for Prevention Research and Epidemiology-BIPS, 28359 Bremen, Germany; fl[email protected] 5 Human Genomics Research Group, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland; per.hoff[email protected] 6 Institute of Human Genetics, Division of Genomics, Life & Brain Research Centre, University Hospital of Bonn, 53105 Bonn, Germany 7 Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany; [email protected] 8 Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan, Germany 9 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, -
H-Tyrosine-Glycine-Phenylalanine-Glycine-Glycine-OH for the Treatment of Chronic Idiopathic Myelofibrosis
European Medicines Agency Pre-authorisation Evaluation of Medicines for Human Use Document Date: London, 5 October 2009 Doc.Ref.: EMEA/COMP/1579/2003 Rev.1 Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in March 2009 on request of the Sponsor. Committee for Orphan Medicinal Products Public summary of positive opinion for orphan designation of H-Tyrosine-Glycine-Phenylalanine-Glycine-Glycine-OH for the treatment of chronic idiopathic myelofibrosis On 20 October 2003, orphan designation (EU/3/03/167) was granted by the European Commission to Abiogen Pharma S.p.A, Italy, for H-Tyrosine-Glycine-Phenylalanine-Glycine-Glycine-OH for the treatment of chronic idiopathic myelofibrosis. What is chronic idiopathic myelofibrosis? Chronic idiopathic myelofibrosis is a disease in which cancer cells are found in the blood and in the bone marrow. The bone marrow is the spongy tissue inside the large bones in the body. Normally the bone marrow makes cells called “blasts” that mature into several different types of blood cells that have specific functions in the body. These include red cells, white cells and platelets. Red blood cells carry oxygen and other materials to all tissues of the body. White blood cells fight infection. Platelets make the blood clot. When myelofibrosis develops, the bone marrow produces large number of abnormal blood cells. In chronic idiopathic myelofibrosis the abnormal population of cells produce substances that alter the growth media of bone marrow and makes bone marrow very dense and rigid. As the abnormal bone marrow environment is no more adequate for the cells, some migrate to other sites where proliferation and maturation take place. -
(12) Patent Application Publication (10) Pub. No.: US 2007/0254315 A1 Cox Et Al
US 20070254315A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0254315 A1 Cox et al. (43) Pub. Date: Nov. 1, 2007 (54) SCREENING FOR NEUROTOXIC AMINO (60) Provisional application No. 60/494.686, filed on Aug. ACID ASSOCATED WITH NEUROLOGICAL 12, 2003. DSORDERS Publication Classification (75) Inventors: Paul A. Cox, Provo, UT (US); Sandra A. Banack, Fullerton, CA (US); Susan (51) Int. Cl. J. Murch, Cambridge (CA) GOIN 33/566 (2006.01) GOIN 33/567 (2006.01) Correspondence Address: (52) U.S. Cl. ............................................................ 435/721 PILLSBURY WINTHROP SHAW PITTMAN LLP (57) ABSTRACT ATTENTION: DOCKETING DEPARTMENT Methods for screening for neurological disorders are dis P.O BOX 105OO closed. Specifically, methods are disclosed for screening for McLean, VA 22102 (US) neurological disorders in a Subject by analyzing a tissue sample obtained from the subject for the presence of (73) Assignee: THE INSTITUTE FOR ETHNO elevated levels of neurotoxic amino acids or neurotoxic MEDICINE, Provo, UT derivatives thereof associated with neurological disorders. In particular, methods are disclosed for diagnosing a neu (21) Appl. No.: 11/760,668 rological disorder in a subject, or predicting the likelihood of developing a neurological disorder in a Subject, by deter (22) Filed: Jun. 8, 2007 mining the levels of B-N-methylamino-L-alanine (BMAA) Related U.S. Application Data in a tissue sample obtained from the subject. Methods for screening for environmental factors associated with neuro (63) Continuation of application No. 10/731,411, filed on logical disorders are disclosed. Methods for inhibiting, treat Dec. 8, 2003, now Pat. No. 7,256,002. -
Taurine and Osmoregulation: Taurine Is a Cerebral Osmoprotective Molecule in Chronic Hypernatremic Dehydration1
003 1-3998/88/2301-0035$02.00/0 PEDIATRIC RESEARCH Vol. 23, No. 1, 1988 Copyright 0 1988 International Pediatric Research Foundation, Inc. Printed in US.A. Taurine and Osmoregulation: Taurine Is a Cerebral Osmoprotective Molecule in Chronic Hypernatremic Dehydration1 HOWARD TRACHTMAN, RANDY BARBOUR, JOHN A. STURMAN, AND LAURENCE FINBERG Departments of Pediatrics and Clinical Chemistry, State University of New York, Health Science Center at Brooklyn; and the Department of Developmental Biochemistry, Institute for Basic Research in Developmental Disabilities, Staten Island, New York ABSTRACT. We studied the effect of 8-wk dietary taurine ative during more prolonged hypernatremia, namely the intra- depletion on the vulnerability to hypernatremic dehydra- cellular accumulation of osmoprotective molecules. These sol- tion in postweanling kittens. While experimental taurine utes, previously referred to as "idiogenic" (3), consist in part of depletion was not associated with increased susceptibility amino acids, taurine in particular (4). If rapid rehydration is to acute hypernatremia (1.5 M NaCl/NaHC03 35 ml/kg attempted, these molecules cannot exit from the cells quickly body weight, single injection), there was an increase in enough and cellular swelling may ensue due to the sudden mortality (five of seven versus one of seven, p = 0.05) and reversal of the osmolal gradient. seizure activity (three of seven versus none of seven, p = The present studies were designed in kittens to assess the role 0.08) in taurine-depleted compared to taurine-replete kit- of taurine as a cerebral osmoprotective molecule in CHD. These tens rendered chronically hypernatremic over 96 h. Fur- animals synthesize little taurine owing to low levels of CSAD thermore, there was a significant decrease in brain cell activity (5, 6). -
Taurine Conjugated Bile Acids in Healthy Subjects
Gut: first published as 10.1136/gut.24.3.249 on 1 March 1983. Downloaded from Cl1t,I98-3. 24, 2249-252 Postprandial plasma concentrations of glycine and taurine conjugated bile acids in healthy subjects K LINNET Fronti tlh,e Departmen t of (-Ctlnicll (Chew istrrv ktred(riksbe,rg, Hospital. C(openIhagen Dentllark SUMMARY Fasting and postprandial plasma concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic. and deoxvcholic acid were measured by a high pressure liquid chromatography-enzymatic assay in nine healthy subjects. The mean value of each bile acid concentration increased significantly (2 4-4.7 times) in the postprandial period. The total glycine/taurine ratio of 2.5 in the fasting state increased significantly to a maximum value of 3 3 at one to 18 hours postprandially and then declined. This shift in glycine/taurine ratio shows, that the relative increase in concentrations of glvcine conjugates exceeds the relative increase in concentrations of taurine conjugates in the early postprandial period, and supports the view that there is significant absorption of glycine conjugated bile acids from the proximal small intestine. Measurements of fasting and postprandial serum Methods concentrations of individual bile acids have so far been performed by radioimmunoassav or gas SUBJECTS chromatographv.' Before analvsis by aas The study was carried out in nine healthy http://gut.bmj.com/ chromatography the bile acids are deconjugated. so volunteers, four women and five men, with a mean that both free and conjugated bile acids are age of 24 years (interval 17-40 years). The subjects measured and no information is obtained regarding were fasted overnight, and in the morning blood the amino acid of the conjugate (glycine or taurine). -
Systemic Gut Microbial Modulation of Bile Acid Metabolism in Host Tissue Compartments
Systemic gut microbial modulation of bile acid metabolism in host tissue compartments Jonathan R. Swanna,b, Elizabeth J. Wanta, Florian M. Geiera, Konstantina Spagoua, Ian D. Wilsonc, James E. Sidawayd, Jeremy K. Nicholsona,1, and Elaine Holmesa,1 aBiomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom; bDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, The University of Reading, Reading RG6 6AP, United Kingdom; cAstraZeneca, Department of Clinical Pharmacology, Drug Metabolism and Pharmacokinetics; and dAstraZeneca, Global Safety Assessment, Cheshire SK10 4TG, United Kingdom Edited by Todd R. Klaenhammer, North Carolina State University, Raleigh, NC, and approved July 30, 2010 (received for review May 26, 2010) We elucidate the detailed effects of gut microbial depletion on the deconjugation, dehydrogenation, dehydroxylation, and sulfation bile acid sub-metabolome of multiple body compartments (liver, reactions (8) to produce secondary bile acids, which are reabsorbed kidney, heart, and blood plasma) in rats. We use a targeted ultra- and returned to the liver for further processing. performance liquid chromatography with time of flight mass-spec- Historically, bile acids have been primarily viewed as detergent trometry assay to characterize the differential primary and secondary molecules important for the absorption of dietary fats and lipid- bile acid profiles in each tissue and show a major increase in the soluble vitamins in the small intestine and the maintenance of proportion of taurine-conjugated bile acids in germ-free (GF) and cholesterol homeostasis in the liver. However, their role in the antibiotic (streptomycin/penicillin)-treated rats. Although conjugated mammalian system is much broader than this, and they are now bile acids dominate the hepatic profile (97.0 ± 1.5%) of conventional recognized as important signaling molecules with systemic endo- animals, unconjugated bile acids comprise the largest proportion of crine functions. -
Taurine-Deficient Dilated Cardiomyopathy in Dogs October 16Th, 2018
TAURINE-DEFICIENT DCM IN DOGS Taurine-Deficient Dilated Cardiomyopathy in Dogs October 16th, 2018 What is this disease? Dilated Cardiomyopathy (DCM) is a form of heart disease in which the heart muscle becomes weak and the heart becomes enlarged. This results in poor heart function, leading to exercise intolerance, collapse, pale gums, coughing, and panting. Eventually, DCM results in complete heart failure. Many dogs show no symptoms until the disease is quite advanced. DCM may be caused by a genetic predisposition in many breeds of dogs. However, the current concern is that cardiologists have been diagnosing DCM in breeds of dogs not generally genetically predisposed—especially golden retrievers. In July, the FDA issued a warning that certainly types of diets may be contributing to the development of nutritional deficiencies in dogs. The cases reported to the FDA have been patients who have developed taurine-deficient DCM. Taurine is an amino acid that dogs are normally able to synthesize from other amino acids in the their food. Many dog foods also add taurine specifically. Cardiologists noticed a trend that pets who were developing taurine-deficient DCM were mainly eating one of three categories of food: boutique, exotic-ingredient, or grain-free diets. The common link is that these diets contain one or more suspect ingredients: Legumes Potatoes Peas Red potatoes ▹ ▹ To Stay Updated... ▹ Chickpeas ▹ White potatoes ▹ Lentils ▹ Sweet potatoes LHV’s Facebook Page ▹ Soybeans ▹ Beans Facebook group “Taurine- The majority of these companies also do not employ a PhD nutritionist or a Deficient Dilated Cardiomyopathy” veterinary nutritionist, and often these foods have not been subjected to feeding trials on dogs. -
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.