DOCSLIB.ORG

July-August 2010 Volume 32 No

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

The News Magazine of the International Union of Pure and Applied Chemistry (IUPAC) CHEMISTRY International July-August 2010 Volume 32 No. 4 Analogue-Based Drug Design Understanding Climate Change Chemistry 2.0 From the Editor CHEMISTRY International hile joking over our iconic “C” logo for the 2011 International Year The News Magazine of the International Union of Pure and Wof Chemistry, a friend of mine suggested that the “C” should be Applied Chemistry (IUPAC) for Communication. “Yes,” I replied, and from there we went on debating the many communication challenges we all experience in our professional www.iupac.org/publications/ci and personal worlds. We agreed that most chemists are not at the forefront of exploiting Managing Editor: Fabienne Meyers communication opportunities readily available Production Editor: Chris Brouwer in the online world. Fortunately, we noted, Design: pubsimple there are “explorer chemists” out there who do adapt selected technologies, which then All correspondence to be addressed to: percolate into our world, bringing unforeseen Fabienne Meyers benefits to how we do things. It may be true IUPAC, c/o Department of Chemistry that other scientific communities embrace Boston University new tools much faster, but in the end, I am Metcalf Center for Science and Engineering sure we will get there. A new generation of chemists will undoubtedly 590 Commonwealth Ave. bring along new tools, some transferred from other social contexts. Boston, MA 02215, USA The discussion changed course when we realized that there are many folks, including specialists in communication, who are very inter- E-mail: [email protected] ested in the behavior of chemists and their challenges in communicat- Phone: +1 617 358 0410 ing. One key reference I recommend reading is a recent commentary Fax: +1 617 353 6466 titled “Communicating Chemistry” by Theresa Velden and Carl Lagoze, published in Nature Chemistry on 1 December 2009 (Vol 1, p. 673–678; Printed by: doi:10.1038/nchem.448), and the related white paper. Cadmus Communications, Easton, PA, USA Related to this topic, I was delighted by the suggestions from Javier Garcia-Martinez, one of our youngest members and an advocate of new Subscriptions communication opportunities. On page 4, he offers CI readers his views on Six issues of Chemistry International (ISSN 0193- Chemistry 2.0 and how new social networking tools can bring folks closer 6484) will be published bimonthly in 2010 (one to chemistry. Javier’s enthusiasm is palpable. He shares with us his favorite volume per annum) in January, March, May, July, sites and apps, and highlights the many educational opportunities. September, and November. The 2010 subscrip- To keep IUPAC moving forward, relevant, and sustainable in today’s tion rate is USD 110.00 for organizations and USD changing world, new voices and views are necessary. I believe it is impor- 50.00 for individuals. Subscription orders may be tant that we keep bringing into our community a wide range of expertise placed directly with the IUPAC Secretariat. Affiliate and folks with “outside the box” attitudes and ideas, and that we continue Members receive CI as part of their Membership to embrace global diversity. Since IUPAC functions through the hard subscription, and Members of IUPAC bodies receive work of dedicated volunteers worldwide, it is up to everyone to step in, CI free of charge. get engaged, and bring change. A perfect opportunity for involvement is upon us: IUPAC is requesting nominations for members of all divisions Reproduction of Articles and commissions (see p. 19 for details). This only happens once ever two Unless there is a footnote to the contrary, repro- years and meanwhile, for now, in an old fashioned way, you won’t find us duction or translation of articles in this issue is on Facebook, nor be able to follow us on Twitter. encouraged, provided that it is accompanied by a reference to the original in Chemistry International. Fabienne Meyers [email protected] Periodicals postage paid at Durham, NC 27709- www.iupac.org/publications/ci 9990 and additional mailing offices. POSTMASTER: Send address changes to Chemistry International, IUPAC Secretariat, PO Box 13757, Research Triangle Park, NC 27709-3757, USA. The image depicted on the cover is a reproduction of the book cover from Analogue-based Drug Discovery—see feature on page 12; reproduced with permission from Wiley-VCH. ISSN 0193-6484 Contents CHEMISTRY International July-August 2010 Volume 32 No. 4 Past President’s Column by Jung-Il Jin 2 Features Chemistry 2.0: Creating Online Communities by Javier Garcia-Martinez 4 Perspectives on Chemistry and Global Climate Change by Fulvio Zecchini and Pietro Tundo 8 Teaching about the Role of Green Chemistry by Fulvio Zecchini et al. 8 Visualizing and Understanding the Science of Climate Change by Peter Mahaffy 11 Analogue-based Drug Discovery by Janos Fischer and C. Robin Ganellin 12 IUPAC Wire IUPAC Announces Winners of the 2010 IUPAC Prizes for Young Chemists 16 IUPAC and InChI Trust Agree Upon Conditions for Collaboration 16 Denis Hamilton to Receive the First International Award for Advances in Crop Protection Chemistry 18 Nominations Requested for Members of IUPAC Divisions and Commissions 19 The Project Place Structure, Processing, and Performance of Ultra-High Molecular Weight Polyethylene 20 Young Ambassadors for Chemistry in Cyprus 21 Guidelines for Measurement of Luminescence Spectra and Quantum Yields of Inorganic Compounds, Metal Complexes, and Materials 21 Technical Guidelines for Isotope Abundances and Atomic Weight Measurements 22 Analytical Chemistry in Action by Brynn Hibbert, secretary of Division V 22 Terminology for Chain Polymerization 24 Provisional Recommendations IUPAC seeks your comments 25 Making an imPACt IUPAC/CITAC Guide: Selection and Use of Proficiency Testing Schemes for a Limited Number of Participants—Chemical Analytical Laboratories 26 The IUPAC-NIST Solubility Data Series: A Guide to Preparation and Use of Compilations and Evaluations 26 Electrochemical Nucleic Acid–Based Biosensors: Concepts, Terms, and Methodology 27 Stamps International, 3 Bookworm Japanese Versions of the IUPAC Red Book and Green Book Available 28 Nanotechnology for the Energy Challenge reviewed by Alan Smith 28 The Future of the Chemical Industry reviewed by Michael J. Droescher 29 Conference Call IUPAC–ACS Collaboration Summit by Katherine Bowman and Francisco Gomez 30 Environmental Best Practices by Maciej Góra 32 Advanced Polymeric Materials by Werner Mormann and Michael Hess 33 Heterocyclic Chemistry by Lisa McElwee-White 35 Where 2B & Y 36 Mark Your Calendar 38 Past President’s Column changes urged by the less patient reformist The IUPAC groups as the guardian of history and tradition, resist- Presidency—A Happy ing the temptation for hasty change as a democratic negotiator restraining himself Recollection from expressing his personal philosophy and by Jung-Il Jin opinions he importance and responsi- In a short time, I learned that the IUPAC president bility of the IUPAC presidency should maintain a relatively flexible stance whenever Tand the multiplicity of its func- he or she has to consider any controversy. A president tions are greater than one might with a charismatic personality and viewpoint can be imagine. Yet, these are rightfully less desirable than one with a practical mind. My own reflected in the status of its position. principle on taking any leadership position, regard- In my term as president, I was helped less of rank, is not simply to be satisfied by the honor and aided by a large group of capa- of being in the leader’s chair but, through diligent ble and dedicated people: members involvement and devotion, to do my best to elevate of the Executive Committee, Bureau, the position. and staff, as well as the IUPAC Officers. A tour of the IUPAC website <www.iupac.org> makes apparent the diversity of the Union’s services After assuming the office of president, it immedi- and operations—and the structural complexity of the ately became evident that frequent and effective com- organization. Then, there are the differing circum- munication among and between the various branches stances and opinions of the NAOs, the diversity of of IUPAC and its constituent members is essential opinions on various technical matters. These are made for the big machine of IUPAC to operate effectively. I more difficult by the inevitable communication barri- quickly became aware that communications between ers that exist in any large international organization. IUPAC and the NAOs and ANAOs needed significant The president’s term of office can make it stressful improvements. To this end, the Membership Relations to make progress and reach goals in his/her limited Committee was formed earlier within the Bureau and period of service. Fortunately, in my case at least, this already is functioning. Moreover, the Council Meetings, feeling disappeared relatively quickly because of the held every two years, do not provide sufficient oppor- good advice provided by the superior analytical minds tunity for sharing ideas and deep discussions among of the IUPAC officers and staff. Among them, the sec- IUPAC and NAO representatives. Such opportunities retary general and the executive director occupy the inevitably will help focus more of IUPAC’s and the most important and demanding positions. To keep NAOs’ attention to areas of mutual concern. the president constantly supplied with information, While the IUPAC presidency carries much pres- advice, and opinions, is only part of their jobs. tige, it also requires considerable work and effort to The wisdom of one’s predecessors is another invalu- respond to the opinions, and needs, of the local units. able asset for the president. But besides these, the Frequently, constituents would like to see IUPAC lead- president should keep his or her eyes and ears wide ership make faster decisions and take firm actions open might they miss any suggestions or complaints without delay.
Recommended publications
  • Significance and Implications of Vitamin B-12 Reaction Shema- ETH ZURICH VARIANT: Mechanisms and Insights

    Significance and Implications of Vitamin B-12 Reaction Shema- ETH ZURICH VARIANT: Mechanisms and Insights

    Taylor University Pillars at Taylor University Student Scholarship: Chemistry Chemistry and Biochemistry Fall 2019 Significance and Implications of Vitamin B-12 Reaction Shema- ETH ZURICH VARIANT: Mechanisms and Insights David Joshua Ferguson Follow this and additional works at: https://pillars.taylor.edu/chemistry-student Part of the Analytical Chemistry Commons, Inorganic Chemistry Commons, Organic Chemistry Commons, Other Chemistry Commons, and the Physical Chemistry Commons CHEMISTRY THESIS SIGNIFICANCE AND IMPLICATIONS OF VITAMIN B-12 REACTION SCHEMA- ETH ZURICH VARIANT: MECHANISMS AND INSIGHTS DAVID JOSHUA FERGUSON 2019 2 Table of Contents: Chapter 1 6 Chapter 2 17 Chapter 3 40 Chapter 4 59 Chapter 5 82 Chapter 6 118 Chapter 7 122 Appendix References 3 Chapter 1 A. INTRODUCTION. Vitamin B-12 otherwise known as cyanocobalamin is a compound with synthetic elegance. Considering how it is composed of an aromatic macrocyclic corrin there are key features of this molecule that are observed either in its synthesis of in the biochemical reactions it plays a role in whether they be isomerization reactions or transfer reactions. In this paper the focus for the discussion will be on the history, chemical significance and total synthesis of vitamin B12. Even more so the paper will be concentrated one of the two variants of the vitamin B-12 synthesis, namely the ETH Zurich variant spearheaded by Albert Eschenmoser.Examining the structure as a whole it is observed that a large portion of the vitamin B12 is a corrin structure with a cobalt ion in the center of the macrocyclic part, and that same cobalt ion has cyanide ligands.
  • The Direct Effects of the Angiotensin-Converting Enzyme

    The Direct Effects of the Angiotensin-Converting Enzyme

    European Journal of Endocrinology (2006) 154 355–361 ISSN 0804-4643 EXPERIMENTAL STUDY The direct effects of the angiotensin-converting enzyme inhibitors, zofenoprilat and enalaprilat, on isolated human pancreatic islets Roberto Lupi, Silvia Del Guerra, Marco Bugliani, Ugo Boggi1, Franco Mosca1, Scilla Torri, Stefano Del Prato and Piero Marchetti Metabolic Unit, Department of Endocrinology and Metabolism, University of Pisa, Ospedale Cisanello, via Paradisa 2, 56100 Pisa, Italy and 1Transplant Unit, Department of Oncology, University of Pisa, Pisa, Italy, Menarini Ricerche SpA, Florence, Italy (Correspondence should be addressed to P Marchetti; Email: [email protected]) Abstract Objective: Data from prospective studies suggest a significant reduction in the risk of new diabetes from drug therapies containing angiotensin-converting enzyme (ACE) inhibitors. Since the renin–angio- tensin system (RAS) has been found locally in several tissues and cells, including pancreatic islets, we hypothesized that the positive metabolic effects of ACE inhibitors may be due to a beneficial action of these compounds on insulin-secreting b-cells. Design and methods: Isolated human pancreatic islets were studied after 24 h of incubation with 22.2 mmol/l glucose, with or without the presence in the incubation medium of 0.5–6.0 mmol/l zofe- noprilat or enalaprilat, ACE inhibitor drugs which differ by the presence of a sulphydryl or a carboxyl group in their structural formula. Functional and molecular studies were then performed to assess insulin secretion, redox balance, mRNA and protein expression. Results: Angiotensinogen, ACE and angiotensin type 1 receptor mRNA expression increased in islets cultured in high glucose; this was similarly prevented by the presence of either ACE inhibitor.
  • Magnesium-Protoporphyrin Chelatase of Rhodobacter

    Magnesium-Protoporphyrin Chelatase of Rhodobacter

    Proc. Natl. Acad. Sci. USA Vol. 92, pp. 1941-1944, March 1995 Biochemistry Magnesium-protoporphyrin chelatase of Rhodobacter sphaeroides: Reconstitution of activity by combining the products of the bchH, -I, and -D genes expressed in Escherichia coli (protoporphyrin IX/tetrapyrrole/chlorophyll/bacteriochlorophyll/photosynthesis) LUCIEN C. D. GIBSON*, ROBERT D. WILLOWSt, C. GAMINI KANNANGARAt, DITER VON WETTSTEINt, AND C. NEIL HUNTER* *Krebs Institute for Biomolecular Research and Robert Hill Institute for Photosynthesis, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, United Kingdom; and tCarlsberg Laboratory, Department of Physiology, Gamle Carlsberg Vej 10, DK-2500 Copenhagen Valby, Denmark Contributed by Diter von Wettstein, November 14, 1994 ABSTRACT Magnesium-protoporphyrin chelatase lies at Escherichia coli and demonstrate that the extracts of the E. coli the branch point of the heme and (bacterio)chlorophyll bio- transformants can convert Mg-protoporphyrin IX to Mg- synthetic pathways. In this work, the photosynthetic bacte- protoporphyrin monomethyl ester (20, 21). Apart from posi- rium Rhodobacter sphaeroides has been used as a model system tively identifying bchM as the gene encoding the Mg- for the study of this reaction. The bchH and the bchI and -D protoporphyrin methyltransferase, this work opens up the genes from R. sphaeroides were expressed in Escherichia coli. possibility of extending this approach to other parts of the When cell-free extracts from strains expressing BchH, BchI, pathway. In this paper, we report the expression of the genes and BchD were combined, the mixture was able to catalyze the bchH, -I, and -D from R. sphaeroides in E. coli: extracts from insertion of Mg into protoporphyrin IX in an ATP-dependent these transformants, when combined in vitro, are highly active manner.
  • 1 INTRODUCTION Corroles Are Tetrapyrrolic Molecules, Maintaining

    1 INTRODUCTION Corroles Are Tetrapyrrolic Molecules, Maintaining

    1 Chapter 1 INTRODUCTION Corroles are tetrapyrrolic molecules, maintaining the skeletal structure of corrin, with its three meso carbon positions and one direct pyrrole-pyrrole linkage, and possessing the aromaticity of porphyrins (see figure 1.1). First reported by Johnson and Kay in 1965[1], corroles were the end product of a many step synthetic scheme, finally being formed by the photocyclization of a,c-biladienes. While this last step was simple, with 20-60% yields, the route to a,c-biladienes was far from easy. Indeed, the overall reaction from readily available starting materials to corrole was a multi-step synthesis, with poor yields in many of the reactions. Thus, while corroles have been known for more than 40 years, research in the field was slow to progress. It wasn’t until the discovery of new synthetic methods for corroles developed in 1999 by different groups working independently that research in this area really started to expand[2]. This is not to say, however, that the field of corrole research was non-existent prior to the development of the new methodologies. While it was slow growing after the initial publication, it was far from stagnant, and many of the interesting properties of corroles were investigated by different groups. Among these properties is their ability to stabilize unusually high formal oxidation states of metal ions, such as iron(IV), cobalt(IV), and cobalt(V)[3, 4]. In fact, one particular corrole available through a method developed by Zeev 2 N N H N N H H N N N N a b N N H H H N N c Figure 1.1.
  • Angiotensin-Converting Enzyme (ACE) Inhibitors

    Angiotensin-Converting Enzyme (ACE) Inhibitors

    Angiotensin-Converting Enzyme (ACE) Inhibitors Summary Blood pressure reduction is similar for the ACE inhibitors class, with no clinically meaningful differences between agents. Side effects are infrequent with ACE inhibitors, and are usually mild in severity; the most commonly occurring include cough and hypotension. Captopril and lisinopril do not require hepatic conversion to active metabolites and may be preferred in patients with severe hepatic impairment. Captopril differs from other oral ACE inhibitors in its rapid onset and shorter duration of action, which requires it to be given 2-3 times per day; enalaprilat, an injectable ACE inhibitor also has a rapid onset and shorter duration of action. Pharmacology Angiotensin Converting Enzyme Inhibitors (ACE inhibitors) block the conversion of angiotensin I to angiotensin II through competitive inhibition of the angiotensin converting enzyme. Angiotensin is formed via the renin-angiotensin-aldosterone system (RAAS), an enzymatic cascade that leads to the proteolytic cleavage of angiotensin I by ACEs to angiotensin II. RAAS impacts cardiovascular, renal and adrenal functions via the regulation of systemic blood pressure and electrolyte and fluid balance. Reduction in plasma levels of angiotensin II, a potent vasoconstrictor and negative feedback mediator for renin activity, by ACE inhibitors leads to increased plasma renin activity and decreased blood pressure, vasopressin secretion, sympathetic activation and cell growth. Decreases in plasma angiotensin II levels also results in a reduction in aldosterone secretion, with a subsequent decrease in sodium and water retention.[51035][51036][50907][51037][24005] ACE is found in both the plasma and tissue, but the concentration appears to be greater in tissue (primarily vascular endothelial cells, but also present in other organs including the heart).
  • ABSTRACT ZHANG, SHAOFEI. Synthesis Of

    ABSTRACT ZHANG, SHAOFEI. Synthesis Of

    ABSTRACT ZHANG, SHAOFEI. Synthesis of Bacteriochlorins and the Full Skeleton of Bacteriochlorophylls. (Under the direction of Professor Jonathan S. Lindsey.) Bacteriochlorins, the core macrocycle ring of natural bacteriochlorophylls, are characterized by their ability to absorb near infrared light (700 – 900 nm), which makes them attractive candidates in variety of photophysical studies and applications. The previously established de novo synthesis, which relies on the acid-catalyzed self-condensation of dihydrodipyrrin–acetal, provides access towards diverse bacteriochlorins, but has its limitations. This dissertation describes the development of new strategies for bacteriochlorin synthesis. Firstly, a route towards previously unknown tetra-alkyl bacteriochlorins (e.g., alkyl = Me, or –CH2CO2Me) is established (Ch. 2). Secondly, explorations of synthetic approaches to unsymmetrically substituted bacteriochlorins through electrocyclic reactions of linear tetrapyrrole intermediates are described. Four new unsymmetrically substituted bacteriochlorins and one new tetradehydrocorrin were produced, albeit in low yields (Ch. 3). Thirdly, a new method to construct bacteriochlorin macrocycle with concomitant Nazarov cyclization to form the annulated isocyclic ring, is established. Five new bacteriochlorins, which are closely anlogues of bacteriochlorophyll a, bearing various substituents (alkyl/alkyl, aryl, and alkyl/ester) at positions 2 and 3 and 132 carboalkoxy groups (R = Me or Et) were constructed in 37−61% yield from the bilin analogues
  • Cheminformatics for Genome-Scale Metabolic Reconstructions

    Cheminformatics for Genome-Scale Metabolic Reconstructions

    CHEMINFORMATICS FOR GENOME-SCALE METABOLIC RECONSTRUCTIONS John W. May European Molecular Biology Laboratory European Bioinformatics Institute University of Cambridge Homerton College A thesis submitted for the degree of Doctor of Philosophy June 2014 Declaration This thesis is the result of my own work and includes nothing which is the outcome of work done in collaboration except where specifically indicated in the text. This dissertation is not substantially the same as any I have submitted for a degree, diploma or other qualification at any other university, and no part has already been, or is currently being submitted for any degree, diploma or other qualification. This dissertation does not exceed the specified length limit of 60,000 words as defined by the Biology Degree Committee. This dissertation has been typeset using LATEX in 11 pt Palatino, one and half spaced, according to the specifications defined by the Board of Graduate Studies and the Biology Degree Committee. June 2014 John W. May to Róisín Acknowledgements This work was carried out in the Cheminformatics and Metabolism Group at the European Bioinformatics Institute (EMBL-EBI). The project was fund- ed by Unilever, the Biotechnology and Biological Sciences Research Coun- cil [BB/I532153/1], and the European Molecular Biology Laboratory. I would like to thank my supervisor, Christoph Steinbeck for his guidance and providing intellectual freedom. I am also thankful to each member of my thesis advisory committee: Gordon James, Julio Saez-Rodriguez, Kiran Patil, and Gos Micklem who gave their time, advice, and guidance. I am thankful to all members of the Cheminformatics and Metabolism Group.
  • Lisinopril (Ethics) Lisinopril Tablets 5 Mg, 10 Mg, 20 Mg

    Lisinopril (Ethics) Lisinopril Tablets 5 Mg, 10 Mg, 20 Mg

    New Zealand Data Sheet Lisinopril (Ethics) Lisinopril Tablets 5 mg, 10 mg, 20 mg 1. NAME OF THE MEDICINAL PRODUCT LISINOPRIL (Ethics) 5 mg, tablet LISINOPRIL (Ethics) 10 mg, tablet LISINOPRIL (Ethics) 20 mg, tablet 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Lisinopril (Ethics) tablets come in three strengths and contain lisinopril dihydrate equivalent to 5 mg, 10 mg or 20 mg lisinopril. 3. PHARMACEUTICAL FORM 5 mg tablet: A light pink coloured, circular, biconvex uncoated tablet. The tablet has a break line and is embossed with ‘5’ on one side and embossed with ‘BL’ on the other side. 10 mg tablet: A light pink coloured, circular, biconvex uncoated tablet. The tablet is embossed with ‘10’ on one side and embossed with ‘BL’ on the other side. 20 mg tablet: A pink, circular, biconvex uncoated tablet. The tablet is embossed with ‘20’ on one side and embossed with ‘BL’ on the other side. Lisinopril dihydrate. The chemical name for lisinopril dihydrate is N-[N-[(1S)-1-carboxy-3- phenylpropyl]-L-lysyl]-L-proline dihydrate. Its structural formula is: C21H31N3O5.2H2O, Molecular weight: 441.53, CAS No.: 83915-83-7 Lisinopril dihydrate is a white to off-white crystalline powder that is soluble in water, sparingly soluble in methanol and practically insoluble in ethanol. A synthetic peptide derivative, lisinopril dihydrate is an oral long acting angiotensin converting enzyme inhibitor. It is a lysine analogue of enalaprilat (active metabolite of enalapril). 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Lisinopril is indicated in the treatment of essential hypertension and in renovascular hypertension. It may be used alone or concomitantly with other classes of antihypertensive agents.

  • Enalaprilat Injection Has Been Used Concomitantly with Digitalis, Beta

    EN-2436 EN-2436 Enalaprilat Injection, USP Enalaprilat Injection, USP Rx only Rx only USE IN PREGNANCY When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, Enalaprilat Injection, USP should be discontinued as soon as possible. See WARNINGS, Fetal/Neonatal Morbidity and Mortality. DESCRIPTION Enalaprilat Injection, USP is a sterile aqueous solution for intravenous administration. Enalaprilat is an angiotensin converting enzyme inhibitor. It is chemically described as (S)-1-[N-(1-carboxy-3-phenylpropyl)-L-alanyl]-L-proline Hospira, Inc., Lake Forest, IL 60045 USA USA 60045 IL Forest, Lake Inc., Hospira, dihydrate. Its molecular formula is C18H24N2O5 • 2H2O and its structural formula is: Printed in USA USA in Printed Enalaprilat is a white to off-white, crystalline powder with a molecular weight of 384.43. It is sparingly soluble in methanol and slightly soluble in water. Each milliliter contains 1.25 mg enalaprilat (anhydrous equivalent); sodium chloride to adjust tonicity; benzyl alcohol, 9 mg, added as a preservative. May contain sodium hydroxide for pH adjustment. CLINICAL PHARMACOLOGY Enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor when administered intravenously, is the active metabolite of the orally administered pro-drug, enalapril maleate. Enalaprilat is poorly absorbed orally. Mechanism of Action Intravenous enalaprilat, or oral enalapril, after hydrolysis to enalaprilat, inhibits ACE in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion.
  • A Primitive Pathway of Porphyrin Biosynthesis and Enzymology in Desulfovibrio Vulgaris

    A Primitive Pathway of Porphyrin Biosynthesis and Enzymology in Desulfovibrio Vulgaris

    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 4853–4858, April 1998 Biochemistry A primitive pathway of porphyrin biosynthesis and enzymology in Desulfovibrio vulgaris TETSUO ISHIDA*, LING YU*, HIDEO AKUTSU†,KIYOSHI OZAWA†,SHOSUKE KAWANISHI‡,AKIRA SETO§, i TOSHIRO INUBUSHI¶, AND SEIYO SANO* Departments of *Biochemistry and §Microbiology and ¶Division of Biophysics, Molecular Neurobiology Research Center, Shiga University of Medical Science, Seta, Ohtsu, Shiga 520-21, Japan; †Department of Bioengineering, Faculty of Engineering, Yokohama National University, 156 Tokiwadai, Hodogaya-ku, Yokohama 240, Japan; and ‡Department of Public Health, Graduate School of Medicine, Kyoto University, Sakyou-ku, Kyoto 606, Japan Communicated by Rudi Schmid, University of California, San Francisco, CA, February 23, 1998 (received for review March 15, 1998) ABSTRACT Culture of Desulfovibrio vulgaris in a medium billion years ago (3). Therefore, it is important to establish the supplemented with 5-aminolevulinic acid and L-methionine- biosynthetic pathway of porphyrins in D. vulgaris, not only methyl-d3 resulted in the formation of porphyrins (sirohydro- from the biochemical point of view, but also from the view- chlorin, coproporphyrin III, and protoporphyrin IX) in which point of molecular evolution. In this paper, we describe a the methyl groups at the C-2 and C-7 positions were deuter- sequence of intermediates in the conversion of uroporphy- ated. A previously unknown hexacarboxylic acid was also rinogen III to coproporphyrinogen III and their stepwise isolated, and its structure was determined to be 12,18- enzymic conversion. didecarboxysirohydrochlorin by mass spectrometry and 1H NMR. These results indicate a primitive pathway of heme biosynthesis in D. vulgaris consisting of the following enzy- MATERIALS AND METHODS matic steps: (i) methylation of the C-2 and C-7 positions of Materials.
  • Biosynthesis of Vitamin B12: Concerning the Origin of the Methine Protons of the Corrin Nucleus (Deuterium Isotope Effects/'3C NMR Spectroscopy) A

    Biosynthesis of Vitamin B12: Concerning the Origin of the Methine Protons of the Corrin Nucleus (Deuterium Isotope Effects/'3C NMR Spectroscopy) A

    Proc. Nati. Acad. Sci. USA Vol. 84, pp. 6616-6618, October 1987 Chemistry Biosynthesis of vitamin B12: Concerning the origin of the methine protons of the corrin nucleus (deuterium isotope effects/'3C NMR spectroscopy) A. IAN SCOTT, MASAHIRO KAJIWARA, AND PATRICIO J. SANTANDER Center for Biological NMR, Department of Chemistry, Texas A&M University, College Station, TX 77843 Communicated by D. H. R. Barton, June 8, 1987 ABSTRACT 13C NMR spectroscopy has been used to C-19 in cobester as discussed above (6). It is also of interest locate six deuterium atoms incorporated biosynthetically on the to note that there is no deuterium at C-10, a position known periphery of the corrin nucleus of vitamin B12 (cyanocobala- to undergo prototropic exchange under acidic conditions (9). min) derived from cells of Propionibacterium shermanii grown Confirmation and extension of the assignments were made in a medium containing 50% 21120 and 13C-enriched 6- by analysis of the spectrum of cyanocobalamin (1) obtained aminolevulinic acid. The implications of these results for the by the same procedure but in the presence of [3-13C]ALA, mechanism of vitamin B12 biosynthesis are discussed, and it is which labels a different set of carbon centers (see Fig. 3). concluded that the same oxidation level of the intermediates is Thus, in addition to an upfield a shift on C-18, p 2H shifts are maintained throughout the biosynthetic pathway, from 8- found at C-2, C-3a, C-7, C-8a, C12, C-13a, and C-18 (Table 2). aminolevulinic acid to corrin. In addition, the C12 P-methyl group has a single deuteron substituent as discerned in the double shift on C12 (from 2H Our knowledge ofthe carbon balance ofthe pathway leading to at C-13 and C12 C1H22H).
  • Catabolism of Tetrapyrroles As the Final Product of Heme Catabolism (Cf Scheme 1)

    Catabolism of Tetrapyrroles As the Final Product of Heme Catabolism (Cf Scheme 1)

    CHEMIE IN FREIBURG/CHIMIE A FRIBOURG 352 CHIMIA 48 (199~) Nr. 9 (Scl'lcmhcr) ns itu Chimia 48 (/994) 352-36/ heme (1), at the a-methene bridge (C(5)) €> Neue Sclnveizerische Chemische Gesellschaft producing CO and an unstable Felli com- /SSN 0009-4293 plex. The latter loses the metal ion to yield the green pigment protobiliverdin IXa (usually abbreviated to biliverdin (2)), which is excreted by birds and amphibia, Catabolism of Tetrapyrroles as the final product of heme catabolism (cf Scheme 1). The iron is recovered in the protein called ferritin and can be reutilized Albert Gossauer* for the biosynthesis of new heme mole- cules. As biliverdin (2) has been recog- nized to be a precursor in the biosynthesis of phycobilins [9], a similar pathway is Abstract. The enzymatic degradation of naturally occurring tetrapyrrolic pigments probably followed for the biosynthesis of (heme, chlorophylls, and vitamin B 12) is shortly reviewed. this class oflight-harvesting chromophores 1. Introduction pounds known so far are synthesized, have Scheme I. Catabolism (!{ Heme ill Mammals been already elucidated, it may be antici- In contrast to the enormous amount of pated that the study of catabolic processes work accomplished by chemists in the will attract the interest of more chemists elucidation of biosynthetic pathways of and biochemists in the near future. secondary metabolites (terpenes, steroids, alkaloids, among others), only a few at- tempts have been made until now to un- 2. Heme Catabolism derstand the mechanisms oftheirdegrada- tion in living organisms. A possible rea- It has been known for over half a cen- son for this fact is the irrational association tury that heme, the oxygen-carrier mole- of degradation (catabolism: greek Kara= cule associated with the blood pigment down) with decay and, thus, with unattrac- hemoglobin, is converted in animal cells tive dirty colors and unpleasant odors.