DOCSLIB.ORG

The Biological Laboratory

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Biological Laboratory LONG ISLAND BIOLOGICAL ASSOCIATION ANNUAL REPORT OF THE BIOLOGICAL LABORATORY COLD SPRING HARBOR LONG ISLAND, NEW YORK 1939 LONG ISLAND BIOLOGICAL ASSOCIATION INCORPORATED 1924 ANNUAL REPORT OF THE BIOLOGICAL LABORATORY FOUNDED 1890 FIFTIETH YEAR 1939 SCIENTIFIC ADVISORY COMMITTEE J. H. Bodine, Chairman,State University of Iowa Harold A. Abramson,College of Physicians and Surgeons, Columbia University Edgar Allen, Yale University,School of Medicine Stanley A. Cain, Universityof Tennessee Robert Chambers, WashingtonSquare College, New York University Harry A. Charipper,Washington Square College, New York University Kenneth S. Cole, College of Physiciansand Surgeons, Columbia University William H. Cole, Rutgers University Henry S. Conard, GrinnellCollege George W. Corner, Universityof Rochester, School of Medicine and Dentistry W. J. Crozier, Harvard University Charles B. Davenport, Carnegie Institution of Washington Alden B. Dawson, Harvard University S. R. Detwiler, College of Physicians and Surgeons,Columbia University Hugo Fricke, The Biological Laboratory Robert Gaunt, Washington Square College, New York University A. J. Grout, Newfane, Vt. Ross G. Harrison, Yale University Hans 0. Haterius, Wayne University, College of Medicine S.I. Kornhauser, University of Louisville Medical School Duncan A. Maclnnes, The Rockefeller Institute for Medical Research fHarold Mestre, Bard College Stuart Mudd, University of Pennsylvania, School of Medicine Hans Mueller, Massachusetts Institute of Technology J.S. Nicholas, Yale University W. J. V. Osterhout, The Rockefeller Institute for Medical Research Eric Ponder, The Biological Laboratory Asa A. Schaeffer, Temple University Herman T. Spieth, College of the City of New York 'Charles R. Stockard, Cornell University Medical College W. W. Swingle, Princeton University Ivon R. Taylor, Brown University Harold C. Urey, Columbia University H. E. Walter, Brown University ADVISORY COMMITTEE ON BIOPHYSICS AND PHYSIOLOGY W. J. V. Osterhout, Chairman J. H. Bodine W. J. Crozier t Deceased 2 THE LONG ISLAND BIOLOGICAL ASSOCIATION President Vice-President and Treasurer Arthur W. Page Marshall Field Vice-President Secretary W. J. V. Osterhout Charles B. Davenport BOARD OF DIRECTORS To serve until 1943 Charles M. Bleecker Cold Spring Harbor, N. Y. Marshall Field Huntington, N. Y. Ross G. Harrison Yale University Wilton Lloyd-Smith Huntington, N. Y. Arthur W. Page Cold Spring Harbor, N. Y. William K. Vanderbilt Centerport, N. Y. H. E. Walter Brown University To serve until 1942 Robert Chambers New York University S. R. Detwiler College of Physicians and Surgeons John Schiff Oyster Bay, N. Y. Henry C. Taylor Cold Spring Harbor, N. Y. Harold C. Urey Columbia University Willis D. Wood Huntington, N. Y. To serve until 1941 C. B. Davenport Carnegie Institution of Washington Henry Hicks Westbury, N. Y. Stuart Mudd University of Pennsylvania, Medical School Robert Cushman Murphy American Museum of Natural History Acosta Nichols Oyster Bay, N. Y. Eric Ponder The Biological Laboratory John K. Roosevelt Glen Cove, N. Y. To serve until 1940 W. H. Cole Rutgers University W. J. Crozier Harvard University Oliver B. James Cold Spring Harbor, N. Y. Mrs. Van Santvoord Merle-Smith Oyster Bay, N. Y. W. J. V. Osterhout Rockefeller Institute tCharles R. Stockard Cornell Medical College W. W. Swingle Princeton University t Deceased Members of the Long Island Biological Association Founders By contribution of atleast $5,000 in money or property fMrs. Eugene Blackford John & Mary Markle Foundation Carnegie Corporation fWilliam J. Matheson Mrs. Ethel Clyde Mrs. Van Santvoord Merle-Smith f Henry W. deForest J. P. Morgan Mrs. Leonard Elmhirst Acosta Nichols Marshall Field Mrs. Acosta Nichols f Dr. Walter B. James Arthur W. Page Mrs. Walter B. James Rockefeller Foundation -Walter Jennings John M. Schiff fjohn D. Jones --Mortimer L. Schiff Mrs. Otto H. Kahn William K. Vanderbilt Russell C. Leffingwell Wawepex Society Wilton Lloyd-Smith fCol. T. S. Williams fRobert B. Woodward Patrons By contribution of at least $500 flames C. Ayer -Anton G. Hodenpyl fFrank L. Babbott Mrs. Walter Jennings fEugene Blackford --Frank S. Jones Charles M. Bleecker f Oliver L. Jones Miss Rosina Boardman Alfred Ephraim Kornfeld 'Nicholas F. Brady 'Miss Mabelle F. Lane John Chase Russell C. Leffingwell fThomas Cochran Gerald M. Livingston W. R. Coe Mrs. Wilton Lloyd-Smith Paul D. Cravath Van Santvoord Merle-Smith Charles B. Davenport A. G. Milbank Mrs. Charles B. Davenport -Ogden L. Mills John W. Davis fWilliam H. Nichols, Jr. Mrs. Henry W. deForest Mrs. George Nichols fRobert deForest --Henry F. Noyes Mrs. Robert W. deForest Isaac R. Oeland 'Cleveland H. Dodge Frederick B. Pratt fF. N. Doubleday fGeorge D. Pratt W. E. Erhart fHarold I. Pratt S. A. Everitt Herbert L. Pratt f Edward Floyd-Jones --Cornelia Prime Childs Frick Victor Rakowsky Hugo Fricke f Oran W. Rice f Edward S. Harkness John K. Roosevelt fMrs. E. H. Harriman fW. Emlen Roosevelt 'Reginald G. Harris fMrs. W. Emlen Roosevelt 1- A. Augustus Healy Walter J. Salmon August Heckscher Carl J. Schmidlapp t Deceased 4 Donald Scott fWalter J. Whipple 'Clarence W. Seamans William C. Whitney Foundation Howard C. Smith George Whitney Henry L. Stimson --Mrs. Timothy S. Williams Henry C. Taylor Willis D. Wood fLouis C. Tiffany Mrs. Willis D. Wood SustainingMembers David Aboff Alexander Forbes Harold A. Abramson Childs Frick Winthrop W. Aldrich Ralph W. Gerard Justin M. Andrews Susan A. Green Anonymous Frederick S. Hammett Annette L. Bacon D. S. Hart line Frank Balduzzi Henry Hicks E. Farrar Bateson Miner C. Hill H. A. Baylis Hudson Hoagland Frederick Bernheim Gail H. Holliday Charles M. Bleecker Davenport Hooker T. Bache Bleecker G. Beekman Hoppin Edward D. Blum Mrs. S. C. W. Hoppin Harold F. Blum Clarence A. Horn Dean Burk Harrison R. Hunt Edward S. Castle 0. L. Inman Mc Keen Cattell Oliver B. James John Chase Mrs. Walter B. James Edward D. Churchill Herbert H. Jasper George L. Clark Mrs. Walter Jennings Mrs. Ethel Clyde Everett C. Jessup Barnett Cohen Alfred Kornfeld William H. Cole S.I. Kornhauser Gilbert Colgate, Jr. Anna Lansing Henry S. Conard Joseph Lilienthal, Jr. Paul Cushman Gerald Livingston C. E. Cutting Wilton Lloyd-Smith Charles B. Davenport Lewis G. Longsworth Hallowell Davis William S. Lord John W. Davis Duncan A. Maclnnes F. Trubee Davison Mrs. Van Santvoord Merle-Smith Henry P. Davison fHarold Mestre H. C. Denturk Leonor Michaelis Abigail C. Dimon A. M. Monnier Ferdinand Eberstadt Louis de B. Moore Charles Edge Mrs. Louis de B. Moore Mrs. Leonard K. Elmhirst Henry S. Morgan Wallace 0. Fenn J. P. Morgan Marshall Field Junius S. Morgan, Jr. Ernst Fischer Laurence S. Moyer Deceased 5 Stuart Mudd Phyllis Stanley Hans Mueller Joseph H. Stickler Acosta Nichols Henry L. Stimson George Nichols Harley L. Stowell Charles Packard F. H. Swett Arthur W. Page George F. Sykes G. H. Parker T. Campbell Takami Frederick B. Pratt Masaharu Tange fHarold I. Pratt Henry C. Taylor Henry S. Pratt Ivon R. Taylor Richardson Pratt James B. Taylor C. Ladd Prosser Isabel H. Tuthill Otto Rahn Mrs. John Upston Walter M. Rankin William K. Vanderbilt Nicolas Rashevsky Emilia M. Vicari Oscar W. Richards Roy A. Waggener Harry C. Robb Mrs. Roy A. Waggener Louis A. Robb George Wald John K. Roosevelt H. E. Walter Alfred Sapone Wawepex Society Asa A. Schaeffer Mrs. Charles H. Welles John M. Schiff Helen M. Wells Carl Schmidlapp Herman Wientjes Francis 0. Schmitt Alice W. Wilcox Julius Schwartz Bess M. Williams Schwartz Brothers Willis D. Wood Donald Scott W. Wilton Wood Ida Sit ler Sewall Wright Carl C. Spiedel Mrs. Sewall Wright Young Brothers The following, though not members of the Long Island Biological Association, have contributed to the Land and Endowment Fund: E. Le Grand Beers Acosta Nichols, Jr. Albert De Silver 'George Lane Nichols J. G. Dettmer C. J. Peabody William G. Loew James H. Post John Hill Morgan f W. A. Putnam Herman Stutzer t Deceased 6 WOMEN'S COMMITTEE PresidentMrs. Van Santvoord Merle-Smith Vice-PresidentMrs. F. Huntington Babcock SecretaryMrs. Fairman R. Dick Chairman, House CommitteeMrs. Percy H. Jennings Chairman, Membership CommitteeMrs. Russell C. Leffingwell Benefactors (By contribution or $100 or more) Mrs. F. Huntington Babcock Mrs. Walter Jennings Mr. George T. Bowdoin Mrs. Van Santvoord Merle-Smith Mrs. G. Beekman Hoppin Mrs. Acosta Nichols Mrs. Roland Redmond Sustaining Members (By contribution of $10or more) Mrs.Francis D. Bartow Mrs. Henry James Mrs.Wyllys R. Betts Mrs. Oliver B. James Mrs.Kenneth S. Boardman Mrs. Walter B. James Mrs.George T. Bowdoin Mrs. Percy H. Jennings Mrs.Trowbridge Calloway Mrs. Otto Kahn Mr.C. T. Church Mrs. Hugh Knowlton Mrs.C. T. Church Mrs. Russell C. Leffingwell Mrs.Henry P. Davison Mrs. Ray Morris Mrs.Henry L. deForest Mrs. George Nichols Mrs.Henry W. deForest Mrs. Paul Pennoyer Mrs.Robert W. deForest Miss Isabel Peters Mrs.Alvin Devereux Mrs. Harold I. Pratt Mrs.A. H. Diebold Mrs. Lansing P. Reed Mrs.Frank N. Doubleday Mrs. Gordon Rentschler Mrs.John Foster Dulles Mrs. Philip J. Roosevelt Mrs.Walter Farwell Mrs. Theodore Roosevelt Mrs.GeorgeS.Franklin Mrs. Stanley M. Rumbough Mrs.Childs Frick Mrs. Donald Scott Mrs.William B. Given Mrs. E. R. Stettinius Mrs.Winston Hagen Mrs. Henry L. Stimson Mrs.Paul Hammond Mrs. Frances M. Weld -Mrs.D. F. Houston Miss Bess M. Williams Mrs. WillisD. Wood I Deceased 7 Members (By contribution of $5) Mrs.Charles E. Ames Miss Elizabeth V. T. Jones Mrs.Henry Anderson Mrs. Frederick R. King Mrs.J. Howland Auchincloss Mrs. Victor W. Knauth Mrs.Daniel Bacon Mrs. Wilton Lloyd-Smith Mrs.Arthur Ballantine Mrs. Graham Lusk Mrs.August Belmont Mrs. Henry J. Mali Mrs.Harry Benkard Mrs. Robert B. Meyer Mrs.Charles Bleecker Mrs. Francis T. Nichols Mrs.T. Bache Bleecker Mrs. J. W. T. Nichols MissRosina Boardman Mrs. William H. Nichols, Jr. Mrs.Herbert Bodman Mrs. D. Chester Noyes Mrs.George E. Brower Mrs. D. Grennell Noyes Mrs.Henry E.
Load more

Recommended publications
  • Single Molecule Enzymology À La Michaelis-Menten
    Single molecule enzymology à la Michaelis-Menten Ramon Grima1, Nils G. Walter2 and Santiago Schnell3* 1 School of Biological Sciences and SynthSys, University of Edinburgh, Edinburgh, UK 2 Department of Chemistry, University of Michigan, Ann Arbor, Michigan, USA 3 Department of Molecular & Integrative Physiology, Department of Computational Medicine & Bioinformatics, and Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, Michigan, USA * To whom the correspondence should be addressed. E-mail: [email protected] Review article accepted for publication to FEBS Journal special issue on Enzyme Kinetics and Allosteric Regulation 1 Abstract In the past one hundred years, deterministic rate equations have been successfully used to infer enzyme-catalysed reaction mechanisms and to estimate rate constants from reaction kinetics experiments conducted in vitro. In recent years, sophisticated experimental techniques have been developed that allow the measurement of enzyme- catalysed and other biopolymer-mediated reactions inside single cells at the single molecule level. Time course data obtained by these methods are considerably noisy because molecule numbers within cells are typically quite small. As a consequence, the interpretation and analysis of single cell data requires stochastic methods, rather than deterministic rate equations. Here we concisely review both experimental and theoretical techniques which enable single molecule analysis with particular emphasis on the major developments in the field of theoretical stochastic enzyme kinetics, from its inception in the mid-twentieth century to its modern day status. We discuss the differences between stochastic and deterministic rate equation models, how these depend on enzyme molecule numbers and substrate inflow into the reaction compartment and how estimation of rate constants from single cell data is possible using recently developed stochastic approaches.
    [Show full text]
  • Covalent Modification of Reduced Flavin Mononucleotide in Type-2 Isopentenyl Diphosphate Isomerase by Active-Site-Directed Inhibitors
    Covalent modification of reduced flavin mononucleotide in type-2 isopentenyl diphosphate isomerase by active-site-directed inhibitors Takuya Nagaia,1, Hideaki Unnob,1, Matthew Walter Janczakc,1, Tohru Yoshimuraa, C. Dale Poulterc,2, and Hisashi Hemmia,2 aDepartment of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan; bDivision of Chemistry and Materials Science, Graduate School of Engineering, Nagasaki University, Bunkyo-machi, Nagasaki, Nagasaki 852-8521, Japan; and cDepartment of Chemistry, University of Utah, 315 South 1400 East RM2020, Salt Lake City, UT 84112 Contributed by C. Dale Poulter, October 11, 2011 (sent for review July 9, 2011) Evidence for an unusual catalysis of protonation/deprotonation by not detect signals for putative radical intermediates (9). Attempts a reduced flavin mononucleotide cofactor is presented for type-2 to inhibit the enzyme by incubation with a cyclopropyl analogue isopentenyl diphosphate isomerase (IDI-2), which catalyzes isomer- of IPP, designed to rearrange to a homoallylic structure by a ization of the two fundamental building blocks of isoprenoid bio- radical clock mechanism, were unsuccessful (12, 13). Instead, the synthesis, isopentenyl diphosphate and dimethylallyl diphosphate. analogue was an alternate substrate that isomerized to the cor- The covalent adducts formed between irreversible mechanism- responding DMAPP derivative without a cyclopropylcarbinyl- based inhibitors, 3-methylene-4-penten-1-yl diphosphate or 3-oxi- homoallyl radical rearrangement. ranyl-3-buten-1-yl diphosphate, and the flavin cofactor were inves- Mechanism-based inhibitors of IDI-1, which are activated by tigated by X-ray crystallography and UV-visible spectroscopy. Both protonation of epoxide and diene moieties in these compounds, the crystal structures of IDI-2 binding the flavin-inhibitor adduct – and the UV-visible spectra of the adducts indicate that the covalent also inactivate IDI-2 (12 15).
    [Show full text]
  • Maud Menten, a Physician and Biochemist
    Maud Menten Canadian medical researcher Maud Menten (1879-1960) has been called the "grandmother of biochemistry," a "radical feminist 1920s flapper," and a "petite dynamo." Not only was she an author of Michaelis-Menten equation for enzyme kinetics (like the plot in indigo in my portrait), she invented the azo-dye coupling for alkaline phosphatase, the first example of enzyme histochemistry, still used in histochemistry imaging of tissues today (which inspired the histology background of the portrait), and she also performed the first electrophoretic separation of blood haemoglobin in 1944! Born in Port Lambton, Ontario, she studied at the University of Toronto, earning her bachelor's in 1904, and then graduated from medical school (M.B., bachelor's of medicine) in 1907. She published her first paper with Archibald Macallum, the Professor of Physiology at U of T (who went on to set up the National Research Council of Canada), on the distribution of chloride ions in nerve cells in 1906. She worked a year at the Rockefeller Institute in New York, where along with Simon Flexner, first director of the Institute, she co-authored a book on radium bromide and cancer, the first publication produced by the Institute - barely 10 years after Marie Curie had discovered radium. She completed the first of two fellowships at Western Reserve University (now Case Western Reserve University), then she earned a doctorate in medical research in 1911 at U of T. She was one of the first Canadian women to earn such an advanced medical degree. She then moved to Berlin (travelling by boat, unfazed by the recent sinking of the Titanic) to work with Leonor Michaelis.
    [Show full text]
  • Leonor Michaelis and Maud Leonora Menten Celebrating 100 Years of the Michaelis–Menten Equation
    ARTICLE-IN-A-BOX Leonor Michaelis and Maud Leonora Menten Celebrating 100 years of the Michaelis–Menten Equation Leonor Michaelis was an honoured German biochemist and Maud Leonora Menten an honoured Canadian pathologist, during the nineteenth century. Though Michaelis sustained his interest in enzymology and biochemistry, Menten moved to pathology and became a renowned pathologist later in her career. The research collaboration of Michaelis and Menten was phenomenal resulting in the celebrated ‘Michaelis–Menten Equation’. Michaelis and Menten’s classic paper titled ‘Die Kinetik der Invertin wirkung’, published in Biochemische Zeitschrift in 1913 marks its centenary this year. This seminal paper which proved vital for the teaching of enzyme kinetics, was acknowledged with so much appreciation and attention that no textbook in biology for undergraduate and graduate students across the world is complete without a discussion of the Michaelis–Menten Equation. An earlier paper by Victor Henri and Brown lacked one important insight which was reported by Michaelis and Menten: that insight was the analysis of reaction in terms of the initial rate. Michaelis and Menten introduced the concept of measuring the initial activity of the enzyme by mixing it with substrate so that product accumulation would not inhibit the activity. Leonor Michaelis (1875–1949) Leonor Michaelis was born in Berlin, Germany on January 16, 1875. He graduated from the ‘humanistic’ Koellnisches Gymnasium in 1893. This gymnasium was special as unlike the other humanistic gymnasiums, it also included chemistry and physics labs which were not in general use and it was only the keen initiative of two professors that enabled interested students learn the subjects.
    [Show full text]
  • Maud Leonora Menten
    Regulars Past Times A woman at the dawn of biochemistry Maud Leonora Menten Athel Cornish-Bowden Ask an average biochemist who was the first to realize that variant proteins could be detected by (Bioénergétique et Ingénierie electrophoresis and sedimentation, and had used this understanding to recognize different forms of des Protéines, CNRS and haemoglobin, the reply would probably refer to Linus Pauling and his work on sickle cell disease. Yet, Aix-Marseille Université, although this work was certainly important, that would be the wrong answer, because Maud Leonora France) and John Lagnado Menten, who sometimes seems to be remembered for one paper only, had this idea several years (Honorary Archivist, the before him, and used it to recognize the differences between foetal and adult haemoglobin1. She was Biochemical Society) unfortunate, however, in that her paper appeared in war time, and was eclipsed a few years later by a far more high-profile study2. In 2013 we celebrate two important centenaries not only of Director, and later the person who appointed Leonor the admission of women to the Biochemical Society (why Michaelis to his position there. With Flexner and James W. did it take so long?), but also of the publication of a paper Jobling, she wrote a book (the first monograph emanating by Maud Menten, who was one of the first women to leave from the Rockefeller Institute) on the effects of radium her mark in biochemistry, with a paper that is cited more bromide on tumours of animals, published in 1910 – often in the 21st Century than it was in the 20th.
    [Show full text]
  • Chemical Reactor Design
    Chemical Reactor Design Youn-Woo Lee School of Chemical and Biological Engineering Seoul National University 155-741, 599 Gwanangro, Gwanak-gu, Seoul, Korea ywlee@snu. ac.kr http://sfpl. snu. ac. kr 第7章 化學反應裝置設計 Chemical Reactor Design Reaction Mechanisms , Pathways, Bioreactions and Bioreactors Seoul National University Objective Discuss the pseudo-steady-state-hypothesis and explain how it can be used to solve reaction engineering problems Write reaction pathways for complex reactions. Explain what an enzyme is and how it acts as a catalyst. Describe Michealis-Menten enzyme kinetics and rate law along with its temperature dependence. Discss h ow t o di stin gui sh th e diff er ent t ypes of enz yme inhibition. Discuss stages of cell growth and rate laws used to describe growth. Write material balances on cells, substrates, and products in bioreactors to size chemostats and plot concentration-time trajectoriesin batch reactors. Describe how physiologically-based pharmocokinetic models can be used to model alcohol metabolism. Seoul National University 7.1 Active Intermediates and Nonelementary Rate law • Elementary rate law - the reaction order of each species is identical with the stoichiometric coefficient of that species for the reaction as written n rA kC A • Non-elementary rate law - no direct correspondence between reaction order and stoichiometry 3 / 2 CH CHO CH + CO r kC 3 4 CH 3CHO CH 3CHO k C C 3/ 2 1 H 2 Br2 H2+Br+ Br2 2HBr rHBr CHBr k2CBr Seoul National University Non-elementary Reaction Non-elementary rate laws involve a number of elementary reactions and at least one active intermediate.
    [Show full text]
  • Enzyme Kinetics at the Molecular Level∗
    GENERAL ARTICLE Enzyme Kinetics at the Molecular Level∗ Arti Dua The celebrated Michaelis–Menten (MM) expression provides a fundamental relation between the rate of enzyme cataly- sis and substrate concentration. The validity of this classical expression is, however, restricted to macroscopic amounts of enzymes and substrates and, thus, to processes with negligi- ble fluctuations. Recent experiments have measured fluctu- ations in the catalytic rate to reveal that the MM equation, though valid for bulk amounts, is not obeyed at the molecu- Arti Dua is an Associate lar level. In this review, we show how new statistical measures Professor in the Indian of fluctuations in the catalytic rate identify a regime in which Institute of Technology Madras. She is a theoretical the MM equation is always violated. This regime, character- chemist, working in the area ized by temporal correlations between enzymatic turnovers, of stochastic reaction is absent for a single enzyme and is unobservably short in the dynamics and statistical classical limit. mechanics of complex fluids. 1. Classical Enzyme Kinetics Enzymes are biological catalysts that accelerate chemical reac- tions manyfold, without getting consumed in the catalytic pro- cess. Several biological processes involving the conversion of substrates to products, thus, rely crucially on the catalytic activity of enzymes. Specific enzymes control and regulate a wide range of life-sustaining processes that vary from digestion, metabolism, absorption, and blood clotting to reproduction. While specificity Keywords depends on the detailed chemical structure of enzyme proteins, Biological catalysts, enzymes, rate kinetics, stochastic enzyme the rate at which the enzymes carry out the catalytic conversion kinetics, Michaelis–Menten depends less on their chemical structure but more on the physical mechanism, enzymatic velocity, parameters, including the amounts of enzymes, substrates, tem- molecular noise.
    [Show full text]
  • Lecture 12 (Pdf)
    Computer Modeling (Physical Chemistry) of Enzyme Catalysis, Metalloenzymes Lubomír Rulíšek, Martin Srnec Institute of Organic Chemistry and Biochemistry AS CR J. Heyrovský Institute of Physical Chemistry AS CR, Prague, Czech Republic Computer Modeling of Chemical Reactions and Enzyme Catalysis 1 Outline Physical Chemistry of Enzyme Catalysis - (Enzymatic) Reaction Rate and Order - Michaelis-Menten (and Enzyme) Kinetics Metals in Enzymology (Theoretical Bioinorganic Chemistry) - Stability Constants, Selectivity - Spin-States in Biochemistry - Crystal Field/Ligand Field Theories - DFT vs. WFT Methods (Accuracy and Pitfalls) - Relativistic Effects (Mild Introduction) 2 Computer Modeling of Chemical Reactions and Enzyme Catalysis 3 Computer Modeling of Chemical Reactions and Enzyme Catalysis Chemical reaction: A + B + C + … → {P} Typical rate equation: v = [ ] [ ] [ ] … x… reaction order with respect to A x + y + z +… overall reaction order Reaction order is not always equivalent to stoichiometry and can be determined only experimentally; allows to hypothesize reaction mechanism, Knowledge of R.O. may suggest the rate-determining step (RDS) (= RLS) Elementary Reaction: single reaction step, single transition state Reaction order is then equivalent to stoichiometry 4 Computer Modeling of Chemical Reactions and Enzyme Catalysis First order reactions The reaction rate depends on a single reactant and the x = 1 + − + Example: SN1 reaction ArN2 + X → ArX + N2, the rate equation is v = k[ArN2 ] Second order reactions x + y + … = 2 A + B + … → {P} can be e.g. v = k[A]2 or v = k[A][B] 2 Example: NO2 + CO → NO + CO2 is v = k[NO2] − − − SN2: CH3COOC2H5 + OH → CH3COO + C2H5OH is v = k[CH3COOC2H5 ][OH ] Pseudo-first order reactions If the concentration of one of the reactant stays constant [B] = [B]0 (e.g.
    [Show full text]
  • Dr Maud Menten (March 20, 1879 – July 17, 1960) Was a Canadian Physician-Scientist Who Made Significant Contributions to Enzyme Kinetics and Histochemistry
    Dr Maud Menten (March 20, 1879 – July 17, 1960) was a Canadian physician-scientist who made significant contributions to enzyme kinetics and histochemistry. Her name is associated with the famous Michaelis–Menten equation in biochemistry. Maud Menten was born in Port Lambton, Ontario and studied medicine at the University of Toronto (B.A. 1904, M.B. 1907, M.D. 1911, Ph.D., 1916). She was among the first women in Canada to earn a medical doctorate. She completed her thesis work at University of Chicago. At that time women were not allowed to do research in Canada, so she decided to do research in other countries such as the United States and Germany. In 1912 she moved to Berlin where she worked with Leonor Michaelis and co-authored their paper in Biochemische Zeitschrift which showed that the rate of an enzyme-catalyzed reaction is proportional to the amount of the enzyme-substrate complex. This relationship between reaction rate and enzyme– substrate concentration is known as the Michaelis–Menten equation. After studying with Michaelis in Germany she entered graduate school at the University of Chicago where she obtained her PhD in 1916. Her dissertation was titled "The Alkalinity of the Blood in Malignancy and Other Pathological Conditions; Together with Observations on the Relation of the Alkalinity of the Blood to Barometric Pressure". Menten worked at the University of Pittsburgh (1923–1950), becoming Assistant Professor and then Associate Professor in the School of Medicine and head of pathology at the Children's Hospital of Pittsburgh. Her final promotion to full Professor, in 1948, was at the age of 69 in the last years of her career.
    [Show full text]
  • The Course of Hermann Aron's
    MAX-PLANCK-INST I T U T F Ü R W I SSENSCHAFTSGESCH I CHTE Max Planck Institute for the History of Science 2009 PREPRINT 370 Shaul Katzir From academic physics to invention and industry: the course of Hermann Aron’s (1845–1913) career Shaul Katzir From academic physics to invention and industry: the course of Hermann Aron’s (1845-1913) career Hermann Aron had an unusual career for a German physicist of the Imperial era. He was an academic lecturer of physics, an inventor, a founder and the manager of a company for electric devices, which employed more than 1,000 employees. Born in 1845 to a modest provincial Jewish family, Aron went through leading schools of the German educational system, received a doctorate in physics and in 1876 the venia legendi - teaching privilege, with which he became a Privatdozent (lecturer) at Berlin university. However, rather than becoming a university professor - the desired goal of this career track - he turned to technology and then industry with the invention of an electricity meter and the foundation of a successful company for its development and manufacture in 1883. By 1897 he owned four sister companies in Berlin, Paris, London, and Vienna-Budapest and manufacturing factories in these cities as well as in Silesia. While in the twentieth century such a career trajectory of a university teacher was not the common case, it was even less so in the late nineteenth century in physics; in many respects it was unique. Aron’s was not the case of a newly qualified doctor hired by industry.
    [Show full text]
  • WILLIAM MANSFIELD CLARK August 17,1884-January 19,1964
    NATIONAL ACADEMY OF SCIENCES WILLIAM MANSFIELD C LARK 1884—1964 A Biographical Memoir by H U BERT BRADFORD V ICKERY Any opinions expressed in this memoir are those of the author(s) and do not necessarily reflect the views of the National Academy of Sciences. Biographical Memoir COPYRIGHT 1967 NATIONAL ACADEMY OF SCIENCES WASHINGTON D.C. WILLIAM MANSFIELD CLARK August 17,1884-January 19,1964 BY HUBERT BRADFORD VICKERY ILLIAM MANSFIELD CLARK, late DeLamar Professor of Phys- Wiological Chemistry in The Johns Hopkins University School of Medicine, was a biochemist to whom accuracy in the measurement of physicochemical quantities and in the state- ment of the conclusions to be drawn from them was an abiding and controlling principle. Throughout a long life of research, beginning as a student with summer work at Woods Hole, Clark devoted himself to measurements, to the design and improvement of apparatus with which the measurements were made, and to the exposition of the results in papers and books uniformly characterized by clarity of expression and thorough- ness of treatment. His book The Determination of Hydrogen Ions, the first edition of which appeared in 1920, brought about what amounted to a revolution in bacteriological labora- tories and exerted a profound influence upon all aspects of biochemistry where the measurement and control of acidity are matters of importance. With characteristic modesty, Clark denied in the preface to the first edition that he had any special qualification for writing the book. In commenting on it in later life, he wrote, "This book put in convenient form what anyone could have found in the literature if he took the trouble to search," and indeed the principles developed in it were largely based upon the fundamental work of Sorensen 2 BIOGRAPHICAL MEMOIRS and of Michaelis.
    [Show full text]
  • In Memory of Professor Leonor Michaelis in Nagoya: Great Contributions to Biochemistry in Japan in the first Half of the 20Th Century ⇑ Toshiharu (Toshi) Nagatsu
    FEBS Letters 587 (2013) 2721–2724 journal homepage: www.FEBSLetters.org In memory of Professor Leonor Michaelis in Nagoya: Great contributions to biochemistry in Japan in the first half of the 20th century ⇑ Toshiharu (Toshi) Nagatsu Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan article info abstract Article history: Leonor Michaelis spent the years of 1922–1926 as Professor of Biochemistry of the Aichi Medical Col- Received 18 March 2013 lege (now Graduate School of Medicine, Nagoya University) in Nagoya, Japan. Michaelis succeeded in Revised 15 April 2013 gathering many bright young biochemists from all over Japan into his laboratory, and made tremen- Accepted 15 April 2013 dous contributions to the promotion of biochemistry in Japan. Michaelis was invited to many places Available online 27 April 2013 in Japan to present lectures over those years. Kunio Yagi, who was Professor of Biochemistry at Edited by Athel Cornish-Bowden Nagoya University in the second half of the 20th century, succeeded in crystallizing the ‘‘Michaelis’’ enzyme–substrate complex. Historically, Michelis has had an enormous impact on biochemistry in Japan. Keywords: Michaelis Ó 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Nagoya Japan 1. Introduction The invitation for Michaelis to become Professor of Biochemis- try at the Medical School in Nagoya was also mentioned in an auto- Leonor Michaelis (1875–1949; Figs. 1 and 2) spent the years of biographical memoir of Michaelis in the NATIONAL ACADEMY OF 1922–1926 as Professor of Biochemistry of the Aichi Medical Col- SCIENCES, USA in 1958 [6].
    [Show full text]