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Biochemistry ofS-Adenosylmethionine and Related
Compounds
Proceedings of a Conference held atthe Lake of the Ozarks (Missouri)
on October 26-29, 1981
Organized by
EARL USDIN2924 N. Oxford StreetA rlington, VA 22207
RONALD T BORCHARDTDepartment of Biochemistry
University of KansasLawrence. KS 66044
CYRUS R CREVELINGLaboratory of Bioorganic Chemistry
National Institute of Arthritis.Metabolism and Digestive Diseases
Bethesda . M D 20205
M
© The contributors, 1982Softcover repri nt of the hardcover 1st edit ion 1982
All rights reserved . No part of this publication may be reproduced ortransmitted, in any form or by any means , without permission.
First published 1982 byScientific and Medical DivisionMACMILLAN PRESS LTD .London and BasingstokeCompanies and representativesthroughout the world
ISBN 978-1-349-06345-1001 10.1007/978-1-349-06343-7
ISBN 978-1-349-06343-7 (eBook)
Contents
~~rJi&:,~~~~: : : : : : : : : : : : : : : : : : : : : : : : :: : : : : : : : ::: : : : : : : : : : : : : : : : : : : : : : : :: : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : <i~I Introduction
S-Adenosylamino acids 30 years later: 1951-1981 . GiulioCantoni
2 Protein Methylation
3
Biological function and mechanism of cytochrome c methylation . Woon Ki Paikand Jamal Farooqui. 13
Turnover of methyl groups in histones . Klaus Hempel 23
Methylation of ribosomal proteins L3 and LI I in Escherichia coli.CharlesColsonand Jacques Lhoest. 31
Enzymatic carboxyl methyl esterification of proteins: Studies on sickleerythrocyte membrane. Sangduk Kim. Jai-Youl Ro, Caterina Manna and VictorG. Glushko. 39
Inh ibition of protein carboxyl methyl esterification by 5'-methyithioadenosine.Patrizia Galletti, Adriana Oliva, Caterina Manna, Diego lngrosso and MariaCarteni-Farina. 49
The protein-carboxyl rnethylating-demethylating system: Modulation of proteinfunction. Claude Gagnon. 55
Protein carboxymethylation in mur ine neuroblastoma; Effect of methyl-transferase inhibitors. Bernard L Mirk in and Robert F O'Dea. 65
Carboxylethylation of rat pancreatic acinar cell zymogen granule membraneproteins. Seymour Heisler and Herman Lambert. 71
Protein methylation in the yeast Saccharomyces cerevisiae. Eric Costers, FrancoiseHespel, Jacques Lhoest and Charles Colson. 75
Why is ribosomal protein LI I of Escherichia coli methylated? Jacques Lhoest,Francoise Hespel, Jean F Lontie, Eugenio Andrade, Colette Digneffe, CharlesColson. 79
The complex nature of methyl-accepting chemotaxis proteins of enteric bacteria.GeraldL Hazelbauer, Peter Engstrom and Shigeaki Harayama. 83
iii
Regulation of the level of methylation of a protein involved in bacterialchemotaxis . Roy A Black , Ann C Hobson and Julius Adler. 91
Methylation of receptors in chemotaxis of bacteria. Elizabeth A Wang andDaniel E Koshland, Jr. 99
3 Phospholipid Methylation
Overviews on phospholipid methylation . Fusao Hirata. 109
The conversion of phosphatidylethanolamine to phosphatidylcholine in animalcells . Dennis E Vance, Francois Audubert and P Haydn Pritchard. 119
Conversion of phosphatidylethanolamine to phosphatidylcholine by themethylation pathway in brain, and relation with the membrane structure.R Mozzi, D Siepi, V Andreoli and G Porcellati. 129
Partial purification and properties of phosphatidylethanolaminemethyl transferase system from mouse liver microsomes . Yasuhlto Tanaka . 139
Deacylation-reacylation and membrane phospholipid methylation. G Y Sun,L Foudin, 0 M-C Der, and K P Shieh . 143
The pharmacological inhibition of phospholipid methylation. Peter K Chiangand Sanford J Shattil. 149
Phospholipid methylation and cholinergic neurons. Jan K Blusztajn, Steven HZeisel and Richard J Wurtman. ISS
The effects of methylation inhibitors on depolarization-dependent exocytosis,phospholipid methylation, and protein carboxymethylation in clonalpheochromocytoma cells. Carolyn S Rabe and Richard McGee , Jr . 165
An activation mechanism of platelet phospholipases. Reiji Kannagi. 173
Receptor mediated regulation of phospholipid methyltransferase activity. Jose MMato, Susana Alemany, Merche Garcia Gil, Dolores Marin Cao, Isabel Varelaand Jose G Castano . 187
Inhibition of norepinephrine uptake by inhibitors of methylation . Marc K Sametand Charles 0 Rutledge. 195
Rat basophilic leukemia cell lines defective in phospholipid methyltransferaseenzymes: Reconstitution by hybridization of IgE-mediate CaH influx ,phospholipid methylation and histamine release . Reuben P Siraganian, AnneMctiivney, Fulton T Crews , Fusao Hirata and Julius Axelrod. 199
4 DNA Methylation
Biological roles of DNA methylation . An overview . Hamilton 0 Smith. 205
On the stability of DNA substituted with 5-azacytosine. Thomas W Sneider. 213
Mechanism of inhibition of DNA methyltransferase by 5-azacytosine substitutedDNA. Judith K Christman, Francine Creusot and George A cs. 223
Effects of xylosyladenine and other inhibitors of methylation on induction ofmurine erythroleukemia cells. Charles Garrell and Nicholas M Kredich. 231
The mechanism of DNA methylation by the restriction endonuclease from E.coli K Robert Yuan , Jean Burckhardt. Jane Weisemann and Daniel L Hamilton. 239
DNA methylation in Escherichia coli. M G Marinus. 249
iv
Organization of the trmD gene in E. coli K 12. Anders S Bystrom andGlenn R Bjork . 255
Methylation at specific sites in integrated adenovirus DNA plays a role in generegulation . W Doerfler. L Vardimon.T Kuhlmann and I Kruczek. 259
Effect of DNA methylation in vitro on the expression of SV40 and VSPV.D Simon. I Tischer, H Wagner, E Werner and H Kroger. 267
Effect of N'-merhyladenine (m6a) content in DNA on spontaneous reversion innon-glucosylated phage T2gt" : Evidence for base analog mutagen activity.Stanley Hattman, Anna Iannotti and Samuel Schlagman . 275
Inhibitory model of methylation in carcinogen modified DNA.A Pfohl-Leszkowicz, R P P Fuchs, G Dirheimer and C E Salas. 279
The effect of the chronic administration of liver carcinogens and tumorpromoters on the hepatic levels of S-adenosylmethionine in rats . Lionel APoirier, Narayan Shivapurkar, Camille L Hyde and Yves B Mikol. 283
5 r- and mRNA Methylation
Effects of cycloleucine on mitochondrial RNA. Donald T Dubin, Christine MGreen and Daniel L Prince. 289
Effect of dimethylation of two adjacent adenines on the structure of 16S RNA .PH van Knippenberg and R van Charldorp. 297
Post-translational methylations of ribosomal proteins in Escherichia coli.Jean-Herve Alix. 303
Ribosomal RNA methylation and resistance to the antibiotic thiostrepton.Jill Thompson and Eric Cundliffe. 309
Methylation of snRNAs and 18S rRNA of Novikoff hepatoma. Yong C Choi,Ramachandra Reddy and Harris Busch. 313
Small RNPs in eucaryotic cells . J P Hendrick, S M Mount, J Rinke. S L Wolin,M D Rosa. E Gottlieb, M R Lerner and J A Steitz. 321
Messenger RNA methylation in plants. S Muthukrishnan. 329
Partial purification of the mRNA (guanine-7-) methyltransferase from wheatgerm. C Locht, H Bouchet and J Delcour. 337
Wheat germ mRNA capping and methylating enzymes. Jerry M Keith . DianaGaler and Larry Westreich , 341
Evidence for a role of methylation in the processing of avian retrovirus RNA. CMart in Stoltzfus and Richard W Dane. 345
6 tRNA Methylation
tRNA methylation: On the role of modified nucleosides in transfer-RNA.Helga Kersten. 357
Formation and function of modified nucleosides in bacterial transfer RNA.G R Bjork. A S Bystrom. T G Hagervall, K J Hjalmarsson, K Kjellin-Straby andPH R Lindstrom. 371
A study of the kinetic mechanisms of two enzymes involved in the metabolismof adenosylmethionine. Lee Shugart. 379
v
The ribothymidine content of mammalian elongator tRNAs modulates ternarycomplex ribosomal A site binding . Din Pow Ma , William C Merrick andBruce A Roe. 385
Studies of transfer RNA methylation in cell transformation. Francesco Salvatore,Paola Izzo , Cinzia Traboni, Franca Esposito and Filiberto Cimino. 389
Genetic control of tRNA methylation in inbred mice. Mark Dizik and ElsieWainfan. 399
Methyl-accepting tRNA from mammary tumors . Phoebe S Leboy and Carlos ESalas . 405
Modified nucleosides from transfer ribonucleic acid as tumor markers. FilibertoCimino. Francesco Costanzo. Tommaso Russo, Alfredo Colonna. Franca Espositoand Francesco Salvatore. 409
Relation between polyam ine level and nucleic acid methylation in vivo.W Kersten and M Mach. 413
Methylene-tetrahydrofolate dependent biosynthesis of ribothymidine intransfer-RNA. Jesse C Rabinowitz . 417
7 Small Molecule Methylation
Methylation of small molecules: An overview. Walter Lovenberg. 427
Norepinephrine N-methyltransferase in brain . Ray W Fuller. 437
Biochemical consequences of adrenal phenylethanolamine N-methyltransferase(PNMT) inhibition. Robert G Pendleton. 445
Conformational aspects of binding of substrates and inhibitors ofphenylethanolamine N-meth yltransferase (PNMT). Gary L Grunewald andMichael F Rafferty. 453
The use of phenylethanolamine N-methyltransferase inhibitors in elucidating therole of brain epinephrine in the control of cardiovascular function.Nina Y Liang. Richard E Tessel, Ronald T Borchardt. William C Vincek andGary L Grunewald. 457
Regulatory aspects of S-adenosylmethionine in the periphery and CNS . Dona LWong and Roland D Ciaranello. 461
Aryl N-methyltransferase: Ring methylation of tryptamine. Ellen Sue Lyon andWilliam B Jakoby. 469
Enzymatic O-methylation of norepinephrine: Studies on the site of methylationby high pressure liquid chromatography. Dhiren R Thakker, Kenneth L Kirk andCyrus R Creveling. 473
Relationships between the cellular localization and the physiological function ofcatechol-Ovmethyltransferase. C R Crevelingand B K Hartman . 479
Immunocytochemical localization of catechol-O-methyltransferase in normal andcancerous breast tissues. Michael C Lowe, AfafM Amin and Cyrus R Creveling. 487
Implications of SAM in estrogen metabolism. Giorgio Stramentlnoli, Carlo DiPadova, Maria Gualanoand Mario Frezza. 491
Genetic, cellular, and biochemical analyses of the yeast 1::.24_ sterol
methyltransferase. Mark T McCammon, Colleen A Mcl.ean-Bowen andLeo W Parks . 499
vi
Methylation of nonpolar lipids: Identification and characterization. MartinZatz, Steinar J Engelsen, Yoel Kloog, Peter A Dudley and Sanford PMarkey . 509
I-Methylnicotinamide metabolism in cultured cells. GeorgeS Johnson. 513
8 Mechanism of Enzymatic Methyl Transfer 521
Alkyltransferases: Mechanistic studies and mechanism -based specific inhibitors.James K Coward. 523
Critical factors in the catalysis of transmethylation . a SoL Wong andR L Schowen. 533
Further stereochemical studies on methyl transfer reactions. Heinz G Floss andRonald Woodard. 539
9 Polyamines
Biosynthesis and accumulation of decarboxylated S-adenosylmethionine.Anthony E Pegg, Hannu Poso and Richard A Bennett. 547
Aspsects of polyamine metabolism in relationship to S-adenosylmethioninemetabolism revealed by the use of n-difluoromethylornithine, an effectiveinhibitor of putrescine biosynthesis. Pierre S Mamont, Charles Darzin andJoseph Wagner. 557
Polyamine synthesis and metabolism in normal and virus-infected protoplastsand chloroplasts. Seymour S Cohen. Robert Balint, Ram K Sindhu andD Marcu. 567
The biosynthesis of spermidine as a key regulatory step in the hormonalinduction of milk-protein synthesis in the organ culture of the mouse mammarygland . Takami aka, Nobuyuki Teradaand John W Perry. 577
Alterations in methylation affect polyamine biosynthesis in mouse brain.Raffele Porta. Robert A Schatz and Otto Z Sellinger. 581
10 S-Adenosylmethionine and S-Adenosylhomocysteine
Regulation of S-adenosylmethionine and S-adenosylhomocysteine levels inisolated rat liver. John A Duerre. 595
Adenosylmethionine metabolism in mammalian spermatozoa. H GuyWilliams-Ashman. Richard Hatch and Jerome Seidenfeld. 603
Metabolism of exogenously administered SAM, Mania Galli-Kienle, PaoloGiu/idori, Emilia Catto and GiorgioStramentinoli. 613
Interaction of S-adenosylmethionine with methylenetetrahydrofolate reductase.S Colette Daubner,Elisa C Krapfand Rowena G Matthews. 617
I-Amino-I-cyclopropanecarboxylic acid synthase, a unique SAM-utilizingenzyme. Ronald W Woodward. 621
Concerning the non specificity of methylation inhibitors. Thomas P Zimmerman,Gerald Walberg, Claus J Schmitges, Lowrie M Beacham, Gail S Duncan andRobert D Deeprose. 627
Recent results on biological activities of natural and synthetic analogues ofS-adenosylhomocysteine. F Lawrence. M Vedel, A Raies, P Blanchard. D Shire,J Hildesheim, M Robert-Giro and E Lederer. 637
vii
Adenosine dialdehyde: A potent inhibitor of S-adenosylhomocysteine hydrolase.Ronald T Borchardt. Usha G Patel and Ronnda L Bartel. 645
Inhibition of Rous sarcoma virus mediated cellular transformation by analoguesof S-adenosylhomocysteine. Henry 0 Stone. Jr.. Mark F Frana andRonald T Borchardt. 653
Inactivation of S-adenosylhomocysteine hydrolase: Mechanism and occurrencein vivo in disorders of purine nucleoside catabolism. Michael S Hershfield,W Curtis Small. Ramaswamy Premakumar, Aldo S Bagnara and Joan E Fetter. 657
Inactivation of S-adenosylhomocysteine hydrolase by9-p-D-arabinofuranosyladenine (ara-A) in intact cells. Svein Helland andPer Magne Ueland. 667
Selection of mutant murine lymphoid cells partially deficient inS-adenosylhomocysteine hydrolase. Naoyuki Kamatani, Eric H Willis andDennis A Carson. 671
Hypermethylation in the MSO-epileptogenic brain : Reversal by dilantin orphenobarbital. Robert A Schatz . Timothy E Wilens, Stephen B Tatter andOtto Z Sellinger. 675
Binding of S-adenosylhomocysteine to isolated rat hepatocytes and purifiedplasma membranes from rat liver. Jarle Aarbakke, Per Magne Ueland and AtieBessesen. 679
Differential properties and regulation of methionine adenosyltransferase isoformsfrom the rat. Jerald L Hoffman and Daniel M Sull ivan. 683
Alterations in the substrate specificities of tumor-derived methionineadenosyltransferase isozymes. Janice R Sufrin and J B Lombardini. 687
11 S-Methylthioadenosine
Regulation of cell growth by 5'-methylthioadenosine. Adolph J Ferro. Michael KRisco and Michael W White. 693
Transport of Y-methyltJhioadenosine in human erythrocytes. Vincenzo Zappia ,Fulvio Della Ragine, Giovanna Cacciapuoti, Marina Porcelli. Patrizia Gallettiand Maria Carteni-Farina. 701
5'-Methylthioadenosine phosphorylase as a chemotherapeutic target enzyme.T M Savarese, M Y cs« S H cs« G W Crabtree, D L Dexter, E N Spremulll,J D Stoeckler, P Calabresi and R E Parks . Jr. 709
The importance of methylth ioadenosine phosphorylase deficiency in humanmalignancy . Dennis A Carson and Naoyuki Kamatani. 715
Methylthioribose as a precursor of the carbon chain of methionine.Stanley K Shapiro. 719
Methionine synthesis from 5'-methylthioadenosine in rat liver. Peter SBacklund , Jr. and Roberts A Smith . 723
Author Index 729
Subject Index 732
viii
Preface
Chronologically it was only a relatively short time betweenthe Bethesda Transmethylation Conference (October 1978) and theLake of the Ozarks Transmethylation Conference (October 1981).But that the field has pushed forward and expanded so considerablyin this period that the Missouri conference was warranted and thatanother proceedings volume was worth publishing is demonstratednot only by the quantity but, we hope, the quality of this volume.The quantity is easily gauged by the thickness of this tome (andthere could easily have been twice as many pages if the editorshad not been so adamant both as to the number of contributors andthe space allotted to the individual contributors).
The quality of the contents is a more subjective parameter.It is easy to demonstrate that the chapters are up-to-date : a highproportion of the references are to papers published in 1980, 1981and even 1982 (i.e., in press or in preparation). It is also possible to demonstrate that established peer reviewers have accordedtheir seal of approval to participants (Julius Axelrod and HamiltonSmith have been awarded Nobel Prizes for ' t hei r work; many otherparticipants have received other prestigious awards for their work).And it is possible to demonstrate that there is represented widespread interest and influence by citing the countries represented:Belgium, Canada, France, Germany, Italy, Japan, Netherlands, Norway, Spain, Sweden, United Kingdom, United States. Whether or notall of this was worthwhile and product worthy of the effort, thatis up to you, the reader, to decide.
We do have several regrets. We are sorry that some researchers who obviously should have participated were unable to attendbecause of other commitments - but it is almost impossible to select a date satisfactory to all of a group of overly committed researchers. We regret that it was not possible to allocate suffic-
ix
ient time or sufficient space for the participants to present allof their pertinent material. We regret that it was not possibleto allow the often heated discussions to continue longer but muchmore we regret that it was not possible to include a summary ofthe discussions in this volume. Although reporters did capturethe essence of some of the discussions, the editors decided thatit would be unfair to include some while omitting other stimulating discussions.
To hold a meeting such as the Lake of the Ozarks Conferenceon Transmethylation it is necessary to have a competent OrganizingCommittee, a good support group, an energetic local committee, andan interested roster of participants. These we had - and we shouldlike to acknowledge their help with much thanks.
EXECUTIVE COMMITTEE
Ronald T. Borchardt, Cyrus R. Creveling, Earl Usdin
ORGANIZING COMMITTEE
Above plus : Julius Axelrod, Giulio Cantoni, Roland D. Ciaranello, James K. Coward, Donald T. Dubin, Ray W. Fuller, Boyd Hartman, Fusao Hirata, Helga Kersten, Sangduk Kim, Woon Ki Paik, Anthony Pegg, Francesco Salvatore, Fritz Schlenk, Richard Schowen,Aaron J. Shatkin, Hamilton Smith, Thomas Sneider, Dennis E. Vance,Vincenzo Zappia, Thomas P. Zimmerman.
SUPPORT
The Organizing Committee gratefully acknowledges support fromthe following companies: BioResearch; Burroughs Wellcome Co.; Hoffman LaRoche, Inc. ; Lilly Research Laboratories; Macmillan Publishers, Ltd .; Merck, Sharp and Dohme Research Laboratories; New England Nuclear; Smith Kline and French Laboratories. The supportfrom the Fogarty International Center (NIH); the National Institute of Arthritis, Metabolism and Digestive Diseases; National Cancer Institute; National Institute of General Medical Sciences;National Institute of Mental Health, the University of Kansas Endowment Association; and the Center for Biomedical Research-University of Kansas is also gratefully acknowledged.
LOCAL COMMITTEE
All of the many problems associated with the running of apleasant and productive meeting were beautifully handled by thefollowing staff of volunteers from the University of Kansas:
x
Rhonda Bartel, Jay Hants, Bradley T. Keller, Nina Y. Liang, BozenaMatuszewska, James Monn, Usha G. Patel, Carol L. Pinnick, MichaelF. Rafferty, Marc K. Samet, Smiter Thakker-Varia, Patricia A.Thomas, Su Er Wu-Huskey. These Kansans were aided abetted by themore than full-time efforts of Ms. Pam Borchardt and Ms. CorneliaCreveling. Thanks, thanks, thanks.
ParticipantsJarle AarbakkeDept. of PharmacologyInstitute of Medical BiologyUniversity of Troms~
Troms~, Norway
Jean-Herv~ AlixInst. Biol. Physico-Chim.13, rue Pierre et Marie CurieF-75005 Paris, France
Julius AxelrodNat1. Inst. of Mental HealthNIH, Bldg. 10, Room 2D45Bethesda, MD 20205
Peter S. Backlund, Jr.Nat1. Inst. of Mental HealthNIH, Bldg. 36, Room 3A19Bethesda, MD 20205
Rhonda BartelDept. of BiochemistryUniversity of KansasLawrence, KS 66045
Glenn R. BjBrkDept. of MicrobiologyUniversity of Ume~S-901 87 Ume~, Sweden
Roy BlackDept. of Biochemistry420 Henry MallUniversity of WisconsinMadison, WI 53706
Jan K. BlusztajnRoom 56-245Mass. Inst. of TechnologyCambridge, MA 02139
xi
Ronald T. BorchardtDept. of BiochemistryUniversity of KansasLawrence, KS 66045
Anders BystrBmDept. of MicrobiologyUniversity of Ume~S-90l 87 Ume~, Sweden
Giu1io L. CantoniNatl. Inst. of Mental HealthNIH, Bldg. 36, Room 3A19Bethesda, MD 20205
Dennis A. CarsonDept. of Clinical ResearchScripps Clinic & Res. Found.10666 N. Torrey Pines RoadLa Jolla, CA 92037
Peter K. ChiangDiv. of BiochemistryWalter Reed Army Inst. of Res.Washington, D.C. 20012
Yong C. ChoiDept. of PharmacologyBaylor College of Medicine1200 Moursund AvenueHouston, TX 77030
Judith ChristmanDept. of BiochemistryMt. Sinai School of Medicine1 East lOath StreetNew York, NY 10029
Filiberto Cimino1st. Chimica Bio10gica20 Faco1ta Medicina e ChirurgiaUniversita di Napoli80131 Napoli, Italy
Seymour S. CohenPharmacological Sci. Dept.Health Sciences CenterSUNY at Stony BrookStony Brook, NY 11794
Charles ColsonUnite de CytogenetiquePlace Croix du Sud, 4B-1348 Louvain-la-Neuve,Belgium
James K. CowardDept. of ChemistryRensselaer Polytechnic Inst.Troy, NY 12181
Cyrus R. Creveling4516 Amherst LaneBethesda, MD 20814
J. DelcourUniv. Catholique de LouvainPlace Croix du Sud, 5B-1348 Louvain-la-Neuve,Belgium
Walter DoerflerInst. of GeneticsUniversity of CologneWeyestal 1215000 KBln 41, West Germany
Donald T. DubinDept. of MicrobiologyRutgers Medical SchoolPiscataway, NJ 08854
John A. DuerreDept. of MicrobiologyUniv. of North DakotaGrand Forks, ND 58201
Adolph J. FerroDept. of MicrobiologyOregon State UniversityCorvallis, OR 97331
Heinz G. FlossSchool of PharmacyPurdue UniversityWest Lafayette, IN 47907
Ray W. FullerLilly Research Labs.Indianapolis, IN 46285
Claude GagnonDept. of PharmacologyLaval Univ. Faculty of MedicineSte-Foy, Quebec, Canada GlK 7P4
Patrizia GallettiDept. of BiochemistryUniv. of Naples 1st Med. SchoolVia Constantinopoli 1680138 Napoli, Italy
Marzia Galli-KienleUniv. of Milan Medical SchoolVia Vanvitelli 3220129 Milano, Italy
Gary L. GrunewaldDept. of Medicinal ChemistryUniversity of KansasLawrence, KS 66045
Stanley HattmanDept. of BiologyUniversity of RochesterRochester, NY 14627
Gerald L. HazelbauerDept. of Biochem. & BiophysicsWashington State UniversityPullman, WA 99164
Seymour HeislerNatl. Inst. of Mental HealthNIH, Bldg. 10, Room 2D47Bethesda, MD 20205
Klaus HempelInst. f. Med . StrahlenkundeVersbacher-Str. 5D8700 WUrzburg, West Germany
Michael S. HershfieldDept. of MedicineDuke Univ. Medical CenterDurham, NC 27710
J. P. HendrickDept. of Mol. Biophys. & Biochem.Yale University333 Cedar StreetNew Haven, CT 06510
xii
Francoise Hespel22/304 rue de la NeuvilleAppt. 101348 Louvain-la-Neuve,Belgium
Fusao HirataNatl. Inst. of Mental HealthNIH, Bldg. 10, Room 2D47Bethesda, MD 20205
Jerald L. HoffmanDept. of BiochemistryUniv. of Louisville Health
Sciences CenterLouisville, KY 40292
George S. JohnsonNatl. Inst. of HealthBldg. 37, Room 2E26Bethesda, MD 20205
Naoyuki KamataniDept. of Clinical Res.Scripps Clinic & Res. Fdn.10666 N. Torrey Pines RoadLa Jolla , CA 92037
Reiji KannagiHutchinson Cancer Res. Center1124 ColumbiaSeattle, WA 98104
Jerry M. KeithDept. of BiochemistryNew York Univ. Col. of Dentistry345 E. 24th StreetNew York, NY 10010
Helga KerstenInst. f. Physiol. ChemieFahrstrasse 17D-8520 Erlangen, Germany
Walter KerstenInst. f. Physiol. ChemieFahrstrasse 17D-8520 Erlangen, Germany
Sangduk KimFels Research InstituteTemple Univ. School of MedicinePhiladelphia, PA 19140
Nicholas M. KredichBox 3100Duke Univ. Medical CenterDurham, NC 27710
Hans KdlgerRobert Koch Inst .Nordufer 201 Berlin 65, Germany
Phoebe S. LeboyDept. of Dental BiochemistryUniv . of PennsylvaniaPhiladelphia, PA 19104
Jacques LhoestUnite de CytogenetiquePlace Croix du Sud, 41348 Louvain-la-Neuve, Belgium
Nina Y. LiangDept. of Pharmacol. & Toxicol.University of KansasLawrence, KS 66045
Walter LovenbergNatl. Heart, Lung & Blood Inst.NIH, Bldg. 10, Room 7N262Bethesda, MD 20205
Ellen Sue LyonNIH, Bldg. 10, Room 9Nl09Bethesda, MD 20205
Din-Pow MaDept. of ChemistryUniversity of Oklahoma620 Parrington Oval, Rm 211Norman, OK 73019
Pierre S. MamontCtr. Recerche Merrell Int.16, rue d'Ankara67084 Strasbourg Cedex, France
M.G. MarinusDept. of PharmacologyUniv. of Mass. Medical SchoolWorcester, MA 01605
Jose M. MatoFundacion Jiminez DiazReyes Catolicos 2Madrid 3, Spain
xiii
Rowena MatthewsBiophysics Research Div.University of MichiganAnn Arbor, MI 48109
Richard McGee. Jr.Dept. of PharmacologyGeorgetown UniversityWashington. DC 20007
Bernard L. MirkinDiv. of C1in. PharmacologyUniv. of Minn. Med. SchoolBox 87. Mayo Mem. Bldg.Minneapolis. MN 55455
S. MuthukrishnanDept. of BiochemistryKansas State UniversityManhattan. KS 66506
Robert F. O'DeaDiv . of C1in. PharmacologyUniv. of Minn. Med. SchoolBox 404. Mayo Mem. Bldg.Minneapolis. MN 55455
Takami OkaLBM/NIADDKNIH. Bldg. 10, Room 9B15Bethesda. MD 20205
Woon Ki PaikFe1s Research InstituteTemple Univ. School of MedicinePhiladelphia. PA 19140
Leo W. ParksDept. of MicrobiologyOregon State UniversityCorvallis. OR 97331
Usha G. PatelDept. of BiochemistryUniversity of KansasLawrence. KS 66045
Anthony E. PeggDept. of PhysiologyHershey Medical CenterPenn. State College of Med.Hershey, PA 17033
Robert G. PendletonSmith. Kline & French Labs.P. O. Box 7929Phi1adephia. PA 19101
L.A. PoirierNational Cancer InstituteBldg. 538, Room 205EFrederick, MD 21701
Giuseppe Porce11ati1st. di Chimica Bio1ogicaUniv. di Perugia Po1ic1inicoCasella Posta1e n. 306100 Perugia. Italy
Jesse C. RabinowitzDept. of BiochemistryUniversity of CaliforniaBerkeley, CA 94720
Michael F. RaffertyDept. of Medicinal ChemistryUniversity of KansasLawrence. KS 66045
M. Robert-GeroInst. de Chimie des Sub. Nat.91190 Gif-sur-Yvette, France
Bruce A. RoeDept. of ChemistryUniv. of Oklahoma620 Parrington Oval, Rm 211Norman. OK 73019
Charles O. RutledgeDept. of Pharmaco1. & Toxico1.University of KansasLawrence. KS 66045
Carlos E. SalasDept of Dental Biochem.Univ. of Penna. School of Dental
MedicinePhiladelphia. PA 19104
Francesco Salvatore1st. Chica Biolog~ca
Univ. di Napoli 2 Fac. MedicineVia S. Pansini. 580131 Napoli. Italy
xiv
Marc K. SametDept. of Pharmacol. & Toxicol.University of KansasLawrence, KS 66045
Todd SavareseDept. of MedicineRoger Williams Genl. Hospital828 Chalkstone AvenueProvidence, RI 02908
Robert SchatzDiv. of ToxicologyNortheastern University360 Huntington AvenueBoston, MA 02115
Fritz SchlenkUniv. of Ill. at Chicago CircleChicago, IL 60680
Richard L. SchowenDept. of ChemistryUniversity of KansasLawrence, KS 66045
Otto Z. SellingerMental Health Res. InstituteUniv. of Michigan Med. CenterAnn Arbor, MI 48109
Stanley K. ShapiroDept. of Biological Sci.Univ . of Ill. at Chicago CircleChicago, IL 60680
Lee ShugartBiology DivisionOak Ridge National Lab.Oak Ridge, TN 37830
Dietrich SimonRobert Koch Inst.Nordufer 201 Berlin 65, Germany
Reuben SiraganianNIH, Bldg. 10, Room 2B12Bethesda, MD 20205
Hamilton O. SmithDept. of Mol. BioI. & GeneticsJohns Hopkins U. Medical SchoolBaltimore, MD 21205
Thomas SneiderDept. of BiochemistryColorado State UniversityFort Collins, CO 80526
Martin C. StoltzfusDept. of MicrobiologyUniversity of IowaIowa City, IA 52242
Henry O. Stone, Jr.Dept. of MicrobiologyUniversity of KansasLawrence, KS 66045
Giorgio StramentinoliBioResearch Co.20060 Liscate, Milano, Italy
Janice R. SufrinDept. of Physiol. & BiophysicsWashington Univ. School of Med.St. Louis, MO 63110
Grace Y. SunSinclair Research FarmUniversity of MissouriColumbia, MO 65201
Yasuhito TanakaDept. of ChemistryNational Inst. of Health10-35, Kamiosaki, 2-chomeShinagawa-ku, Tokyo 141, Japan
Dhiren ThakkerNIH, Bldg. 4, Room 206Bethesda, MD 20205
Jill R. ThompsonDept. of Biochem., Adrian Bldg.University of Leicester, U. K.
Per Magne UelandDept. of PharmacologyUniv. of Bergen School of MedicineBergen, Norway
Earl Usdin2924 N. Oxford StreetArlington, VA 22207
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Dennis E. VanceDept. of BiochemistryUniv. of British ColumbiaVancouver BC, Canada V6T 1W5
Peter H. Van KnippenbergDept. of BiochemistryState Univ. of LeidenVassenaarseweg 642333 AL Leiden, The Netherlands
Elsie WainfanNew York Blood Center310 E. 67th StreetNew York, NY 10021
Elizabeth WangBiochemistry DepartmentUniversity of CaliforniaBerkeley, CA 94720
H.G. Williams-AshmanBen May Lab. for Cancer Res.University of Chicago950 E. 59th streetChicago, IL 60637
Dona Lee WongDept. of PsychiatryStanford Univ. Medical CenterStanford, CA 94305
Ronald W. WoodardCollege of PharmacyUniversity of MichiganAnn Arbor, MI 48109
Robert YuanCancer Biology ProgramP. O. Box Bfrederick, MD 21701
Vincenzo Zappia1st. di Chimica Bio1ogicaVia Constantinopo1i 1680138 Napoli, Italy
Martin ZatzNat1. Inst. of Mental HealthNIH, Bldg. 10, Room 2D47Bethesda, MD 20205
Thomas P. ZimmermanDept. of Expt1. TherapyBurroughs We11come Labs.3030 Cornwallis RoadResearch Triangle Park, NC 27709
Abbreviations
3-deazaadenosine3-deaza aristero-
A = adenineAAF = 2-acetylaminofluoreneACC = l-amino-I-cyclopropanecar-
boxylic acidACh = acetylcholineACTH = adrenocorticotrophinAd = adenovirus or adenosylADA = adenosine deaminaseADAP = L-N3-acetyl-2,3-diamino-
propionateAdo = ADO = adenosineAdoCy = S-adenosylcysteineAdoHcy S-adenosylhomocysteineAdoMet S-adenosylmethionineAdoTba S-adenosyl-4-thiobutyric
acidAdoTpa S-adenosyl-3'-thiopro-
pylamineAdox = oxidized adenosineADP = adenosine diphosphateAdR = 2'-deoxyadenosineAH = heptane extract from alcoholALP alkaline phosphataseALT alanine aminotransferaseAME L-aspartate-B-methyl esterAMP adenosine monophosphateANS l-analino-8-naphthalene
sulfonateAPRT = adenine phosphoribosyl-
transferaseAPT = aminopropyltransferaseara-A = adenine arabinosideASV = avian sarcoma ·virusATP = adenosine triphosphateATPase = adenosine triphosphataseAUC = area under the curve5-aza-C = 5-azacytosylaza-CDR = 5-aza-CdR = 5-aza-2'-
deoxycytidine5-azaCR = 5-azacytidine
BL = basophilic leukemia (cells)bp = base pairsBSS = balanced salt solutionBUdR = 5-bromo-2'-deoxyuridine
C = cytosineC3Ado = 3-deaza-adenosinecAMP = cyclic AMP
CAP = chloramphenicolCAR = 5'-chloroadenosineCDPcholine = cytidine 5'-diphos-
phorylcholineCdR = 2'-deoxycytidineCEF = chick embryo fibroblastcGMP = cyclic GMPCh = cholineCH3H~PtGlun = 5-methyl-5,6,7,8
tetrahydropteroyl oligo-a-glutamate
CH3SAdo = S-adenosylmethylthioadenosine
CH3SAdoase = methylthioadenosinenucleoside phosphorylase
cIMP = cyclic inosine monophos-phate
CM = chloroform-methanolCMW = chloroform-methanol-watercmoSu = uridine 5'-oxyacetic
acidCNS = central nervous systemCOMT = catechol O-methyltransfer-
aseConA concavalin ACONH = 2-cyclooctylethanolamineCP = creatine phosphateCSF = cerebrospinal fluidcyt = cytoplasmic
DA = dopaminedAdo = deoxyadenosinedATP = deoxyadenosine triphos-
phateDBP = DNA binding proteindcF = 2'-deoxyformycinDCMB = 2,3-dichloro-a-methylben-
zylaminedcSAM = decarboxylated SAMdCTP = deoxycytidine triphosphateDDT = dichlorodiphenyltrichloro-
ethane3-deaza-Ado3-deaza-Ari
mycinDFMO = DFMeOrn = a-difluorome
thylornithineDG = diacylglycerol2-DG = 2-deoxy-D-glucose
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dGTP = deoxyguanosine triphos-phate
DHBA = 3,4-dihydroxybenzoic acidDHF = dihydrofolateDMSO = dimethylsulfoxideDMTA = 5'-deoxy-5'-dimethylthio
adenosineDNA = deoxynucleic acidDNAase = DNase = deoxyribonuc-
leaseDNPH = dinitrophenylhexatrieneDOC = deoxycholateDOCA = deoxycorticosteroneDOPAC = 3,4-dihydroyphenylacetic
acidDPH = diphenylhydantoinds = double strandeddTMP = deoxythymidine monophos
phatedTTP = deoxythymidine triphos
phateDZA 3-deaza-adenosine
EAA = l-a-ethylamidoaspartateEBSS = Earle's balanced salt
solutionECF = extracellular fluidECoK = E. coli KEDTA = ethylenediamine tetraac
etic acidEE = l7aethinylestradiolEGTA = ethyleneglycol-bis-(a-am
inoethyl ether)-N,N'-tetraacetic acid
EHNA = erythro-9-(2-hydroxy-3-nonyl) adenine
EM = electron microscopyEpi = epinephrine5'-ETFAR = 5'-ethylthio-2-fluoro
adenosine
2-FA = 2-fluoroadenineFAME = fatty acid methyl estersFL = Friend erythroleukemia
GAA = guanidoacetic acidGAA-P = guanidoacetic acid phos
phateGC/MS = gas chromatography/mass
spectrometryGOP guanosine diphosphateGMP = guanosine monophosphate
GMP-E = capping enzyme-guanylatecomplex
GTP = guanosine triphosphateGTPase = guanosine triphosphatase
HAT = hypoxanthine + aminopterin+ thymidine
HAVA = a-hydrazino-o-ornithineHcy = homocysteineHEPES = N-2-hydroxylethylpipera
zine-N'-2-ethanesulfonateHIOMT = hydroxyindole Q-methyl-
transferaseHL-60 = human promyeloidhm5C = 5-hydroxymethylcytosineHMT = histamine N-methyltransfer-
aseHMTB = 2-hydroxy-4-methylthio
butyrateHPLC = high performance (or pres-
sure) liquid chromatographyH4PteGlun = oligo-y-glutamateHT = hydroxytryptamineHTC = hepatoma tissue cultureHTL = homocsteine thiolactone
5'-IAdo = 5'-iodoadenosine5'-IIno = 5'-iodoinosinea,y-imido-ATP = adenosine 5' (a-
y-imido) triphosphate5-IR-l-P = 5-iodoribose-l-phos
phate
kb = kilobaseKMTB = 2-keto-4-methylthiobutyr
ateKRM = Krebs-Ringer-MOPS medium
LMC = lymphocyte-mediated cytol-ysis
LP = lyso-phospholipidsLPC = lysophosphatidylcholineLPE = l-palmitoyl-glycerophospho-
ethanolamine
M = modification (subunit)MAA = L-a-methylamidoaspartatemam5s 2U = 5-methylaminomethyl-
2-thiouridineMAP = methyl acceptor protein(s)MAT = methionine adenosyltrans
ferasem6A = N6-methyladenine
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S = specificity (subunit)S-AdoMet = S-Ado-Met = S-adeno-
sylmethionineSAE = S-adenosylethionineSAH = S-adenosylhomocysteineSAHase = S-adenosylhomocysteine
hydrolaseSAM = S-adenosylmethionineSAM-DC = SAM decarboxylase
R = restriction (subunit)RBL = rat basophilic leukemiaRib-I-P = ribose-I-phosphateR-M = restriction and modifica-
tionRNA = ribonucleic acidRNAase = RNase = ribonucleaseRNP = ribonuceoprotein(s)rRNA = ribosomal RNARSV = Reus sarcoma virusrt = ribothyrnidine
mcmo5u = methyl ester of cmo5u POME = phosphatidyldimethyleth-MCP = methyl-accepting chemotaxis anolamine
protein(s) PE = phosphatidylethanolaminemeA methyladenine PeMT = phosphatidylethanolaminemeC = methylcytosine N-methyltransferaseMEL = murine erythroleukemia PGE = prostaglandin EMeSAdo = 5'-methylthioadenosine PI = phosphatidylinositolMet = MET = methionine Pi = inorganic phosphateMG = monoacylglycerol PKI protein kinase inhibitorMIG = l-methylguanosine PLM = phospholipid methylationMGPG = methylglyoxal bis(guanyl- PLP = pyridoxal phosphate
hydrazone) PMII = protein methylase IImit = mitochondrial PME = protein methylesterase ~MNB = murine neuroblastoma phosphatidyl-N-monomethyleth-MOPS = morpholinopropanesulfonate anolaminernRNA = m-RNA = messenger RNA PMT = phosphomethyltransferasems2i6A = N-6-(~2-isopentyl)-2- ~ phospholipid methyltrans-
methylthioadenosine feraseMSO = L-methionine-sulfoximine PMTase = phospholipid methyl-MTA = 5'-methylthioadenosine or transferase
5'-deoxy-5'-methylthioadenosine PNMT = phenylethanolamine N-meMTAase = methylthioadenosine phos- thyltransferase
phorylase PNP = purine nucleoside phos-MTAPase = 5'-methylthioadenosine phorylase
phosphorylase PPi = inorganic pyrophosphateMTR = 5-methylthioribose PS = phosphatidylserineMTR-l-p = 5-methylthioribose-l- PtdCho phosphatidylcholine
phosphate PtdEth = phosphatidylethanola-MTT = 5'-deoxy-5'-methylthiotu- mine
bercidin PVP-40T = polyvinylpyrrolidinem5u = 5-methyluridine
N-AcO-AAF = N-acetoxy-N-2-acetyl-aminofluorene
NE = norepinephrineNM = norrnetanephrineNMT = norepinephrine N-methyl-
transferaseNP = norparanephrineNucH = nucleophile
ODC = ornithine decarboxylase
PA = phosphatidic acidPAF = platelet activating factorPAGE = polyacrylamide gel elec-
trophoresisPAP = peroxidase-antiperoxidasePB = phenobarbitalPC = phosphatidylcholinePCM = protein-carboxyl methylasePOE = phosphatidyl-N,N-dirnethyl-
ethanolamine
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SAMe = S-adenosylmethionineSCMT = ~2~-sterol-C-methyltrans
feraseSDS = sodium dodecyl sulfateSHR = spontaneously hypertensive
ratsSIBA = S-isobutyryladenosineSIBI = S-isobutylinosinesnRNA = small nuclear RNAsnRNP = small nuclear RNPSP = sulfopropylSpd = spermidineSpm = spermineSS = sickle cell anemiass = single strandedSTH S-tubercidinylhomocysteines~U 4-thiouridine
TBS total (post-prandial) bilesalts
TCA = tricholoroacetic acidTG = thioguanineTHF tetrahydrofolateTLC = thin layer chromatographyTMA = thiomethyladenosinetRNA = transfer mlAtRMAmd = methyl-deficient tRNATYMV = turnip yellow mosaic
virus
VSPV = very small porcine virus
WKY = Wistar-Kyoto (rats)
XAHcy = xylosyl analog of AdoHcyXAMet = xylosyl analog of AdoMetXATP = xylosyl analog of ATP
Zc = zymosan
~ = pseudouridine
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