14. color atlas of biochemistry, 2 nd ed (j koolman, k h roehm)(thieme,2005) - - - pretty good

Color Atlas of Biochemistry, 2nd edition

Color Atlas ofBiochemistrySecond edition, revised and enlarged

Jan KoolmanProfessorPhilipps University MarburgInstitute of Physiologic ChemistryMarburg, Germany

Klaus-Heinrich RoehmProfessorPhilipps University MarburgInstitute of Physiologic ChemistryMarburg, Germany

215 color plates by Juergen Wirth

ThiemeStuttgart New York

All rights reserved. Usage subject to terms and conditions of license.Koolman, Color Atlas of Biochemistry, 2nd edition 2005 Thieme

IV

Library of Congress Cataloging-in-Publication Data

This book is an authorized and updated trans-lation of the 3rd German edition publishedand copyrighted 2003 by Georg Thieme Ver-lag, Stuttgart, Germany. Title of the Germanedition: Taschenatlas der Biochemie

Illustrator: Juergen Wirth, Professor of VisualCommunication, University of Applied Scien-ces, Darmstadt, Germany

Translator: Michael Robertson, BA DPhil,Augsburg, Germany

1st Dutch edition 20041st English edition 19961st French edition 19942nd French edition 19993rd French edition 20041st German edition 19942nd German edition 19971st Greek edition 19991st Indonesian edition 20021st Italian edition 19971st Japanese edition 19961st Portuguese edition 20041st Russian edition 20001st Spanish edition 2004

2005 Georg Thieme VerlagRdigerstrasse 14, 70469 Stuttgart,Germanyhttp://www.thieme.deThieme New York, 333 Seventh Avenue,New York, NY 10001 USAhttp://www.thieme.com

Cover design: Cyclus, StuttgartCover drawing: CAP cAMP bound to DNATypesetting by primustype Hurler GmbH,NotzingenPrinted in Germany by Appl, Wemding

ISBN 3-13-100372-3 (GTV)ISBN 1-58890-247-1 (TNY)

Important note: Medicine is an ever-changingscience undergoing continual development.Research and clinical experience are continu-ally expanding our knowledge, in particularour knowledge of proper treatment and drugtherapy. Insofar as this book mentions anydosage or application, readers may rest as-sured that the authors, editors, and publishershave made every effort to ensure that suchreferences are in accordance with the state ofknowledge at the time of production of thebook. Nevertheless, this does not involve, im-ply, or express any guarantee or responsibilityon the part of the publishers in respect to anydosage instructions and forms of applicationsstated in the book. Every user is requested toexamine carefully the manufacturers leafletsaccompanying each drug and to check, if nec-essary in consultation with a physician orspecialist, whether the dosage schedulesmentioned therein or the contraindicationsstated by the manufacturers differ from thestatements made in the present book. Suchexamination is particularly important withdrugs that are either rarely used or havebeen newly released on the market. Everydosage schedule or every form of applicationused is entirely at the users own risk andresponsibility. The authors and publishers re-quest every user to report to the publishersany discrepancies or inaccuracies noticed. Iferrors in this work are found after publication,errata will be posted at www.thieme.com onthe product description page.

Some of the product names, patents, and reg-istered designs referred to in this book are infact registered trademarks or proprietarynames even though specific reference to thisfact is not always made in the text. Therefore,the appearance of a name without designa-tion as proprietary is not to be construed as arepresentation by the publisher that it is inthe public domain.This book, including all parts thereof, is legallyprotected by copyright. Any use, exploitation,or commercialization outside the narrow lim-its set by copyright legislation, without thepublishers consent, is illegal and liable toprosecution. This applies in particular to pho-tostat reproduction, copying, mimeograph-ing, preparation of microfilms, and electronicdata processing and storage.


VAbout the Authors

Jan Koolman (left) was born in Lbeck, Ger-many, and grew up with the sea wind blowingoff the Baltic. The high school he attended inthe Hanseatic city of Lbeck was one thatfocused on providing a classical education,which left its mark on him. From 1963 to1969, he studied biochemistry at the Univer-sity of Tbingen. He then took his doctorate(in the discipline of chemistry) at the Univer-sity of Marburg, under the supervision of bio-chemist Peter Karlson. In Marburg, he beganto study the biochemistry of insects and otherinvertebrates. He took his postdoctoral de-gree in 1977 in the field of human medicine,and was appointed Honorary Professor in1984. His field of study today is biochemicalendocrinology. His other interests include ed-ucational methods in biochemistry. He is cur-rently Dean of Studies in the Department ofMedicine in Marburg; he is married to an artteacher.Klaus-Heinrich Rhm (right) comes fromStuttgart, Germany. After graduating fromthe School of Protestant Theology in Urachanother institution specializing in classicalstudiesand following a period working inthe field of physics, he took a diploma in bio-chemistry at the University of Tbingen,where the two authors first met. Since 1970,he has also worked in the Department ofMedicine at the University of Marburg. He

took his doctorate under the supervision ofFriedhelm Schneider, and his postdoctoral de-gree in 1980 was in the Department of Chem-istry. He has been an Honorary Professor since1986. His research group is concerned withthe structure and function of enzymes in-volved in amino acid metabolism. He is mar-ried to a biologist and has two children.Jrgen Wirth (center) studied in Berlin and atthe College of Design in Offenbach, Germany.His studies focused on free graphics and illus-tration, and his diploma topic was The devel-opment and function of scientific illustration.From 1963 to 1977, Jrgen Wirth was involvedin designing the exhibition space in theSenckenberg Museum of Natural History inFrankfurt am Main, while at the same timeworking as a freelance associate with severalpublishing companies, providing illustrationsfor schoolbooks, non-fiction titles, and scien-tific publications. He has received severalawards for book illustration and design. In1978, he was appointed to a professorship atthe College of Design in Schwbisch Gmnd,Germany, and in 1986 he became Professor ofDesign at the Academy of Design in Darm-stadt, Germany. His specialist fields includescientific graphics/information graphics andillustration methods. He is married and hasthree children.


VI

Preface

Biochemistry is a dynamic, rapidly growingfield, and the goal of this color atlas is toillustrate this fact visually. The precise boun-daries between biochemistry and relatedfields, such as cell biology, anatomy, physiol-ogy, genetics, and pharmacology, are dif cultto define and, in many cases, arbitrary. Thisoverlap is not coincidental. The object beingstudied is often the samea nerve cell or amitochondrion, for exampleand only thepoint of view differs.For a considerable period of its history, bio-chemistry was strongly influenced by chem-istry and concentrated on investigating met-abolic conversions and energy transfers. Ex-plaining the composition, structure, and me-tabolism of biologically important moleculeshas always been in the foreground. However,new aspects inherited from biochemistrysother parent, the biological sciences, arenow increasingly being added: the relation-ship between chemical structure and biolog-ical function, the pathways of informationtransfer, observance of the ways in whichbiomolecules are spatially and temporally dis-tributed in cells and organisms, and an aware-ness of evolution as a biochemical process.These new aspects of biochemistry are boundto become more and more important.Owing to space limitations, we have concen-trated here on the biochemistry of humansand mammals, although the biochemistry ofother animals, plants, and microorganisms isno less interesting. In selecting the materialfor this book, we have put the emphasis onsubjects relevant to students of human med-icine. The main purpose of the atlas is to serveas an overview and to provide visual informa-tion quickly and ef ciently. Referring to text-books can easily fill any gaps. For readersencountering biochemistry for the first time,some of the plates may look rather complex. Itmust be emphasized, therefore, that the atlasis not intended as a substitute for a compre-hensive textbook of biochemistry.As the subject matter is often dif cult to vis-ualize, symbols, models, and other graphic

elements had to be found that make compli-cated phenomena appear tangible. Thegraphics were designed conservatively, theaim being to avoid illustrations that mightlook too spectacular or exaggerated. Ourgoal was to achieve a visual and aestheticway of representing scientific facts that wouldbe simple and at the same time effective forteaching purposes. Use of graphics softwarehelped to maintain consistency in the use ofshapes, colors, dimensions, and labels, in par-ticular. Formulae and other repetitive ele-ments and structures could be handled easilyand precisely with the assistance of the com-puter.Color-coding has been used throughout to aidthe reader, and the key to this is given in twospecial color plates on the front and rear in-side covers. For example, in molecular modelseach of the more important atoms has a par-ticular color: gray for carbon, white for hydro-gen, blue for nitrogen, red for oxygen, and soon. The different classes of biomolecules arealso distinguished by color: proteins are al-ways shown in brown tones, carbohydrates inviolet, lipids in yellow, DNA in blue, and RNAin green. In addition, specific symbols areused for the important coenzymes, such asATP and NAD+. The compartments in whichbiochemical processes take place are color-coded as well. For example, the cytoplasm isshown in yellow, while the extracellular spaceis shaded in blue. Arrows indicating a chem-ical reaction are always black and those rep-resenting a transport process are gray.In terms of the visual clarity of its presenta-tion, biochemistry has still to catch up withanatomy and physiology. In this book, wesometimes use simplified ball-and-stick mod-els instead of the classical chemical formulae.In addition, a number of compounds are rep-resented by space-filling models. In thesecases, we have tried to be as realistic as pos-sible. The models of small molecules arebased on conformations calculated by com-puter-based molecular modeling. In illustrat-ing macromolecules, we used structural infor-


VIIPreface

mation obtained by X-ray crystallographythat is stored in the Protein Data Bank. Innaming enzymes, we have followed the of -cial nomenclature recommended by theIUBMB. For quick identification, EC numbers(in italics) are included with enzyme names.To help students assess the relevance of thematerial (while preparing for an examination,for example), we have included symbols onthe text pages next to the section headings toindicate how important each topic is. A filledcircle stands for basic knowledge, a half-filled circle indicates standard knowledge,and an empty circle stands for in-depthknowledge. Of course, this classificationonly reflects our subjective views.This second edition was carefully revised anda significant number of new plates wereadded to cover new developments.

We are grateful to many readers for theircomments and valuable criticisms during thepreparation of this book. Of course, we wouldalso welcome further comments and sugges-tions from our readers.

August 2004

Jan Koolman,Klaus-Heinrich RhmMarburg

Jrgen WirthDarmstadt


Contents

Introduction . . . . . . . . . . . . . . . . . . . . 1

BasicsChemistryPeriodic table. . . . . . . . . . . . . . . . . . . . 2Bonds . . . . . . . . . . . . . . . . . . . . . . . . . 4Molecular structure . . . . . . . . . . . . . . . 6Isomerism . . . . . . . . . . . . . . . . . . . . . . 8Biomolecules I . . . . . . . . . . . . . . . . . . . 10Biomolecules II . . . . . . . . . . . . . . . . . . 12Chemical reactions. . . . . . . . . . . . . . . . 14

Physical ChemistryEnergetics . . . . . . . . . . . . . . . . . . . . . . 16Equilibriums . . . . . . . . . . . . . . . . . . . . 18Enthalpy and entropy. . . . . . . . . . . . . . 20Reaction kinetics . . . . . . . . . . . . . . . . . 22Catalysis . . . . . . . . . . . . . . . . . . . . . . . 24Water as a solvent . . . . . . . . . . . . . . . . 26Hydrophobic interactions . . . . . . . . . . . 28Acids and bases . . . . . . . . . . . . . . . . . . 30Redox processes. . . . . . . . . . . . . . . . . . 32

BiomoleculesCarbohydratesOverview. . . . . . . . . . . . . . . . . . . . . . . 34Chemistry of sugars . . . . . . . . . . . . . . . 36Monosaccharides and disaccharides . . . 38Polysaccharides: overview . . . . . . . . . . 40Plant polysaccharides. . . . . . . . . . . . . . 42Glycosaminoglycans and glycoproteins . 44

LipidsOverview. . . . . . . . . . . . . . . . . . . . . . . 46Fatty acids and fats . . . . . . . . . . . . . . . 48Phospholipids and glycolipids . . . . . . . 50Isoprenoids . . . . . . . . . . . . . . . . . . . . . 52Steroid structure . . . . . . . . . . . . . . . . . 54Steroids: overview . . . . . . . . . . . . . . . . 56

Amino AcidsChemistry and properties. . . . . . . . . . . 58Proteinogenic amino acids . . . . . . . . . . 60Non-proteinogenic amino acids . . . . . . 62

Peptides and ProteinsOverview. . . . . . . . . . . . . . . . . . . . . . . 64Peptide bonds . . . . . . . . . . . . . . . . . . . 66Secondary structures . . . . . . . . . . . . . . 68

Structural proteins . . . . . . . . . . . . . . . . 70Globular proteins . . . . . . . . . . . . . . . . . 72Protein folding . . . . . . . . . . . . . . . . . . . 74Molecular models: insulin. . . . . . . . . . . 76Isolation and analysis of proteins . . . . . 78

Nucleotides and Nucleic AcidsBases and nucleotides. . . . . . . . . . . . . . 80RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . 82DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . 84Molecular models: DNA and RNA . . . . . 86

MetabolismEnzymesBasics. . . . . . . . . . . . . . . . . . . . . . . . . . 88Enzyme catalysis . . . . . . . . . . . . . . . . . 90Enzyme kinetics I . . . . . . . . . . . . . . . . . 92Enzyme kinetics II . . . . . . . . . . . . . . . . 94Inhibitors . . . . . . . . . . . . . . . . . . . . . . . 96Lactate dehydrogenase: structure . . . . . 98Lactate dehydrogenase: mechanism . . . 100Enzymatic analysis . . . . . . . . . . . . . . . . 102Coenzymes 1 . . . . . . . . . . . . . . . . . . . . 104Coenzymes 2 . . . . . . . . . . . . . . . . . . . . 106Coenzymes 3 . . . . . . . . . . . . . . . . . . . . 108Activated metabolites . . . . . . . . . . . . . . 110

Metabolic RegulationIntermediary metabolism . . . . . . . . . . . 112Regulatory mechanisms . . . . . . . . . . . . 114Allosteric regulation . . . . . . . . . . . . . . . 116Transcription control . . . . . . . . . . . . . . 118Hormonal control . . . . . . . . . . . . . . . . . 120

Energy MetabolismATP . . . . . . . . . . . . . . . . . . . . . . . . . . . 122Energetic coupling . . . . . . . . . . . . . . . . 124Energy conservation at membranes. . . . 126Photosynthesis: light reactions . . . . . . . 128Photosynthesis: dark reactions . . . . . . . 130Molecular models: membrane proteins . 132Oxoacid dehydrogenases. . . . . . . . . . . . 134Tricarboxylic acid cycle: reactions . . . . . 136Tricarboxylic acid cycle: functions . . . . . 138Respiratory chain . . . . . . . . . . . . . . . . . 140ATP synthesis . . . . . . . . . . . . . . . . . . . . 142Regulation . . . . . . . . . . . . . . . . . . . . . . 144Respiration and fermentation . . . . . . . . 146Fermentations . . . . . . . . . . . . . . . . . . . 148

VIII


Carbohydrate MetabolismGlycolysis . . . . . . . . . . . . . . . . . . . . . . . 150Pentose phosphate pathway . . . . . . . . . 152Gluconeogenesis. . . . . . . . . . . . . . . . . . 154Glycogen metabolism . . . . . . . . . . . . . . 156Regulation . . . . . . . . . . . . . . . . . . . . . . 158Diabetes mellitus . . . . . . . . . . . . . . . . . 160

Lipid MetabolismOverview . . . . . . . . . . . . . . . . . . . . . . . 162Fatty acid degradation . . . . . . . . . . . . . 164Minor pathways of fatty aciddegradation . . . . . . . . . . . . . . . . . . . . . 166Fatty acid synthesis . . . . . . . . . . . . . . . 168Biosynthesis of complex lipids . . . . . . . 170Biosynthesis of cholesterol . . . . . . . . . . 172

Protein MetabolismProtein metabolism: overview . . . . . . . 174Proteolysis . . . . . . . . . . . . . . . . . . . . . . 176Transamination and deamination . . . . . 178Amino acid degradation . . . . . . . . . . . . 180Urea cycle . . . . . . . . . . . . . . . . . . . . . . 182Amino acid biosynthesis . . . . . . . . . . . . 184

Nucleotide MetabolismNucleotide degradation. . . . . . . . . . . . . 186Purine and pyrimidine biosynthesis . . . 188Nucleotide biosynthesis . . . . . . . . . . . . 190

Porphyrin MetabolismHeme biosynthesis . . . . . . . . . . . . . . . . 192Heme degradation . . . . . . . . . . . . . . . . 194

OrganellesBasicsStructure of cells . . . . . . . . . . . . . . . . . 196Cell fractionation . . . . . . . . . . . . . . . . . 198Centrifugation . . . . . . . . . . . . . . . . . . . 200Cell components and cytoplasm . . . . . . 202

CytoskeletonComponents . . . . . . . . . . . . . . . . . . . . . 204Structure and functions . . . . . . . . . . . . 206

Nucleus . . . . . . . . . . . . . . . . . . . . . . . . 208

MitochondriaStructure and functions . . . . . . . . . . . . 210Transport systems . . . . . . . . . . . . . . . . 212

Biological MembranesStructure and components . . . . . . . . . . 214Functions and composition . . . . . . . . . . 216Transport processes . . . . . . . . . . . . . . . 218Transport proteins . . . . . . . . . . . . . . . . 220Ion channels. . . . . . . . . . . . . . . . . . . . . 222Membrane receptors . . . . . . . . . . . . . . 224

Endoplasmic Reticulum and Golgi ApparatusER: structure and function. . . . . . . . . . 226Protein sorting . . . . . . . . . . . . . . . . . . 228Protein synthesis and maturation . . . . 230Protein maturation . . . . . . . . . . . . . . . 232

Lysosomes. . . . . . . . . . . . . . . . . . . . . . 234

Molecular GeneticsOverview . . . . . . . . . . . . . . . . . . . . . . 236Genome . . . . . . . . . . . . . . . . . . . . . . . 238Replication . . . . . . . . . . . . . . . . . . . . . 240Transcription. . . . . . . . . . . . . . . . . . . . 242Transcriptional control . . . . . . . . . . . . 244RNA maturation . . . . . . . . . . . . . . . . . 246Amino acid activation . . . . . . . . . . . . . 248Translation I: initiation . . . . . . . . . . . . 250Translation II: elongation andtermination. . . . . . . . . . . . . . . . . . . . . 252Antibiotics . . . . . . . . . . . . . . . . . . . . . 254Mutation and repair . . . . . . . . . . . . . . 256

Genetic engineeringDNA cloning . . . . . . . . . . . . . . . . . . . . 258DNA sequencing . . . . . . . . . . . . . . . . . 260PCR and protein expression . . . . . . . . . 262Genetic engineering in medicine . . . . . 264

Tissues and organsDigestionOverview . . . . . . . . . . . . . . . . . . . . . . 266Digestive secretions. . . . . . . . . . . . . . . 268Digestive processes . . . . . . . . . . . . . . . 270Resorption . . . . . . . . . . . . . . . . . . . . . 272

BloodComposition and functions . . . . . . . . . 274Plasma proteins. . . . . . . . . . . . . . . . . . 276Lipoproteins . . . . . . . . . . . . . . . . . . . . 278Hemoglobin . . . . . . . . . . . . . . . . . . . . 280Gas transport . . . . . . . . . . . . . . . . . . . 282Erythrocyte metabolism . . . . . . . . . . . 284Iron metabolism . . . . . . . . . . . . . . . . . 286Acidbase balance . . . . . . . . . . . . . . . . 288Blood clotting . . . . . . . . . . . . . . . . . . . 290Fibrinolysis, blood groups . . . . . . . . . . 292

Immune systemImmune response . . . . . . . . . . . . . . . . 294T-cell activation. . . . . . . . . . . . . . . . . . 296Complement system . . . . . . . . . . . . . . 298Antibodies . . . . . . . . . . . . . . . . . . . . . 300Antibody biosynthesis . . . . . . . . . . . . . 302Monoclonal antibodies, immunoassay . 304

IXContents


LiverFunctions. . . . . . . . . . . . . . . . . . . . . . . 306Buffer function in organ metabolism . . 308Carbohydrate metabolism . . . . . . . . . . 310Lipid metabolism . . . . . . . . . . . . . . . . . 312Bile acids . . . . . . . . . . . . . . . . . . . . . . . 314Biotransformations . . . . . . . . . . . . . . . 316Cytochrome P450 systems . . . . . . . . . . 318Ethanol metabolism . . . . . . . . . . . . . . . 320

KidneyFunctions. . . . . . . . . . . . . . . . . . . . . . . 322Urine. . . . . . . . . . . . . . . . . . . . . . . . . . 324Functions in the acidbase balance. . . . 326Electrolyte and water recycling . . . . . . 328Renal hormones. . . . . . . . . . . . . . . . . . 330

MuscleMuscle contraction . . . . . . . . . . . . . . . 332Control of muscle contraction. . . . . . . . 334Muscle metabolism I . . . . . . . . . . . . . . 336Muscle metabolism II . . . . . . . . . . . . . . 338

Connective tissueBone and teeth . . . . . . . . . . . . . . . . . . 340Calcium metabolism . . . . . . . . . . . . . . 342Collagens . . . . . . . . . . . . . . . . . . . . . . . 344Extracellular matrix . . . . . . . . . . . . . . . 346

Brain and Sensory OrgansSignal transmission in the CNS . . . . . . . 348Resting potential and action potential. . 350Neurotransmitters . . . . . . . . . . . . . . . . 352Receptors for neurotransmitters . . . . . . 354Metabolism . . . . . . . . . . . . . . . . . . . . . 356Sight . . . . . . . . . . . . . . . . . . . . . . . . . . 358

NutritionNutrientsOrganic substances . . . . . . . . . . . . . . . 360Minerals and trace elements . . . . . . . . 362

VitaminsLipid-soluble vitamins . . . . . . . . . . . . . 364Water-soluble vitamins I . . . . . . . . . . . 366Water-soluble vitamins II . . . . . . . . . . . 368

HormonesHormonal systemBasics . . . . . . . . . . . . . . . . . . . . . . . . . 370Plasma levels and hormone hierarchy. . 372

Lipophilic hormones. . . . . . . . . . . . . . . 374Metabolism of steroid hormones . . . . . 376Mechanism of action . . . . . . . . . . . . . . 378

Hydrophilic hormones . . . . . . . . . . . . . 380Metabolism of peptide hormones . . . . . 382Mechanisms of action . . . . . . . . . . . . . . 384Second messengers. . . . . . . . . . . . . . . . 386Signal cascades. . . . . . . . . . . . . . . . . . . 388

Other signaling substancesEicosanoids . . . . . . . . . . . . . . . . . . . . . 390Cytokines . . . . . . . . . . . . . . . . . . . . . . . 392

Growth and developmentCell proliferationCell cycle . . . . . . . . . . . . . . . . . . . . . . . 394Apoptosis . . . . . . . . . . . . . . . . . . . . . . . 396Oncogenes . . . . . . . . . . . . . . . . . . . . . . 398Tumors . . . . . . . . . . . . . . . . . . . . . . . . 400Cytostatic drugs . . . . . . . . . . . . . . . . . . 402

Viruses . . . . . . . . . . . . . . . . . . . . . . . . . 404

Metabolic charts . . . . . . . . . . . . . . . . . . 406Calvin cycle . . . . . . . . . . . . . . . . . . . . . 407Carbohydrate metabolism. . . . . . . . . . . 408Biosynthesis of fats andmembrane liquids . . . . . . . . . . . . . . . . 409Synthesis of ketone bodies and steroids 410Degradation of fats and phospholipids . 411Biosynthesis of the essentialamino acids . . . . . . . . . . . . . . . . . . . . . 412Biosynthesis of the non-essentialamino acids . . . . . . . . . . . . . . . . . . . . . 413Amino acid degradation I . . . . . . . . . . . 414Amino acid degradation II. . . . . . . . . . . 415Ammonia metabolism. . . . . . . . . . . . . . 416Biosynthesis of purine nucleotides . . . . 417Biosynthesis of the pyrimidine nucleotidesand C1 metabolism . . . . . . . . . . . . . . . . 418Nucleotide degradation. . . . . . . . . . . . . 419

Annotated enzyme list . . . . . . . . . . . . . 420

Abbreviations . . . . . . . . . . . . . . . . . . . . 431

Quantities and units . . . . . . . . . . . . . . . 433

Further reading . . . . . . . . . . . . . . . . . . 434

Source credits. . . . . . . . . . . . . . . . . . . . 435

Index . . . . . . . . . . . . . . . . . . . . . . . . . . 437

Key to color-coding:see front and rear inside covers

X Contents


Introduction

This paperback atlas is intended for studentsof medicine and the biological sciences. Itprovides an introduction to biochemistry,but with its modular structure it can also beused as a reference book for more detailedinformation. The 216 color plates provideknowledge in the field of biochemistry, ac-companied by detailed information in thetext on the facing page. The degree of dif -culty of the subject-matter is indicated bysymbols in the text:

stands for basic biochemical knowledge indicates standard biochemical knowl-

edge means specialist biochemical knowledge.

Some general rules used in the structure ofthe illustrations are summed up in two ex-planatory plates inside the front and backcovers. Keywords, definitions, explanationsof unfamiliar concepts and chemical formulascan be found using the index. The book startswith a few basics in biochemistry (pp. 233).There is a brief explanation of the conceptsand principles of chemistry (pp. 215). Theseinclude the periodic table of the elements,chemical bonds, the general rules governingmolecular structure, and the structures of im-portant classes of compounds. Several basicconcepts of physical chemistry are also essen-tial for an understanding of biochemicalprocesses. Pages 1633 therefore discuss thevarious forms of energy and their intercon-version, reaction kinetics and catalysis, theproperties of water, acids and bases, and re-dox processes.

These basic concepts are followed by a sec-tion on the structure of the important biomo-lecules (pp. 3487). This part of the book isarranged according to the different classes ofmetabolites. It discusses carbohydrates, lipids,amino acids, peptides and proteins, nucleoti-des, and nucleic acids.

The next part presents the reactionsinvolved in the interconversion of thesecompoundsthe part of biochemistry that iscommonly referred to as metabolism(pp. 88195). The section starts with a dis-cussion of the enzymes and coenzymes, anddiscusses the mechanisms of metabolic regu-lation and the so-called energy metabolism.After this, the central metabolic pathwaysare presented, once again arranged accordingto the class of metabolite (pp.150195).

The second half of the book begins with adiscussion of the functional compartmentswithin the cell, the cellular organelles (pp.196235). This is followed on pp. 236265by the current field of molecular genetics(molecular biology). A further extensive sec-tion is devoted to the biochemistry ofindividual tissues and organs (pp. 266359).Here, it has only been possible to focus on themost important organs and organ systemsthe digestive system, blood, liver, kidneys,muscles, connective and supportive tissues,and the brain.

Other topics include the biochemistry ofnutrition (pp. 360369), the structure andfunction of important hormones (pp.370393), and growth and development(pp. 394405).

The paperback atlas concludes with a seriesof schematic metabolic charts (pp.407419). These plates, which are not accom-panied by explanatory text apart from a briefintroduction on p. 406, show simplified ver-sions of the most important synthetic anddegradative pathways. The charts are mainlyintended for reference, but they can also beused to review previously learned material.The enzymes catalyzing the various reactionsare only indicated by their EC numbers. Theirnames can be found in the systematically ar-ranged and annotated enzyme list (pp.420430).

1Chemistry


Periodic table

A. Biologically important elements

There are 81 stable elements in nature. Fifteenof these are present in all living things, and afurther 810 are only found in particular or-ganisms. The illustration shows the first halfof the periodic table, containing all of the bio-logically important elements. In addition tophysical and chemical data, it also providesinformation about the distribution of the ele-ments in the living world and their abun-dance in the human body. The laws of atomicstructure underlying the periodic table arediscussed in chemistry textbooks.

More than 99% of the atoms in animalsbodies are accounted for by just four ele-mentshydrogen (H), oxygen (O), carbon (C)and nitrogen (N). Hydrogen and oxygen arethe constituents of water, which alone makesup 6070% of cell mass (see p.196). Togetherwith carbon and nitrogen, hydrogen and oxy-gen are also the major constituents of theorganic compounds on which most livingprocesses depend. Many biomolecules alsocontain sulfur (S) or phosphorus (P). Theabove macroelements are essential for all or-ganisms.

A second biologically important group ofelements, which together represent onlyabout 0.5% of the body mass, are present al-most exclusively in the form of inorganic ions.This group includes the alkali metals sodium(Na) and potassium (K), and the alkaline earthmetals magnesium (Mg) and calcium (Ca). Thehalogen chlorine (Cl) is also always ionized inthe cell. All other elements important for lifeare present in such small quantities that theyare referred to as trace elements. These in-clude transition metals such as iron (Fe), zinc(Zn), copper (Cu), cobalt (Co) and manganese(Mn). A few nonmetals, such as iodine (I) andselenium (Se), can also be classed as essentialtrace elements.

B. Electron configurations: examples

The chemical properties of atoms and thetypes of bond they form with each other aredetermined by their electron shells. The elec-tron configurations of the elements are there-fore also shown in Fig. A. Fig. B explains thesymbols and abbreviations used. More de-

tailed discussions of the subject are availablein chemistry textbooks.

The possible states of electrons are calledorbitals. These are indicated by what isknown as the principal quantum numberand by a letters, p, or d. The orbitals arefilled one by one as the number of electronsincreases. Each orbital can hold a maximum oftwo electrons, which must have oppositelydirected spins. Fig. A shows the distributionof the electrons among the orbitals for each ofthe elements. For example, the six electrons ofcarbon (B1) occupy the 1s orbital, the 2s orbi-tal, and two 2p orbitals. A filled 1s orbital hasthe same electron configuration as the noblegas helium (He). This region of the electronshell of carbon is therefore abbreviated asHe in Fig. A. Below this, the numbers ofelectrons in each of the other filled orbitals(2s and 2p in the case of carbon) are shown onthe right margin. For example, the electronshell of chlorine (B2) consists of that of neon(Ne) and seven additional electrons in 3s and3p orbitals. In iron (B3), a transition metal ofthe first series, electrons occupy the 4s orbitaleven though the 3d orbitals are still partlyempty. Many reactions of the transition met-als involve empty d orbitalse. g., redox reac-tions or the formation of complexes withbases.

Particularly stable electron arrangementsarise when the outermost shell is fully occu-pied with eight electrons (the octet rule).This applies, for example, to the noble gases,as well as to ions such as Cl (3s23p6) and Na+

(2s22p6). It is only in the cases of hydrogenand helium that two electrons are alreadysuf cient to fill the outermost 1s orbital.

2 Basics


??

?

??

1s

2s2p

3s3p

3d4s4p

4d5s5p

3d4s

4d5s

4

5

44.96

Sc21

Ar

12

47.88

Ti22

Ar

22

50.94

V23

Ar

32

52.00

Cr24

Ar

42

54.94

Mn25

Ar

52

55.85

Fe26

Ar

62

58.93

Co27

Ar

72

58.69

Ni28

Ar

82

63.55

Cu29

Ar

92

65.39

Zn30

Ar

102

3 4 5 6 7 8 9 10 11 12

1.01

H1

1

63

4.00

He2

2

6.94

Li3

19.01

Be 24

10.81

B5

21

12.01

C6

He22

14.01

N7

He23

1.4

16.00

O8

He24

25.5

19.00

F9

He25

20.18 He

Ne10

26

HeHe He

22.99 Ne

Na 111 0.03

24.31

Mg12

Ne

2

0.01

26.98 Ne

Al13

21

28.09

Si14

Ne

22

30.97 Ne

P15

23

0.22

32.07

S16

Ne

24

0.05

35.45

Cl17

Ne

25

0.03

39.95

Ar18

26

39.10 Ar

K19

1

0.06

40.08 Ar

Ca20

2

0.31

69.72

Ga31

Ar

1021

72.61

Ge32

Ar

1022

74.92

As33

Ar

1023

78.96

Se34

Ar

10

79.90

BrAr

1025

83.80

Kr36

Ar

1026

126.9

I53

Kr1025

24 35

Ne

1

2

3

4

5

1 2 13 14 15 16 17 18

30.97

P15 0.22

?

Ne

23

9.5

95.94

Mo42

Kr42

s p ds p s p

[Ne][Ar]

4

3

2

1

3

2

1

4

3

2

1

3

2

1

[He]

Alkalineearths Halogens

Alkalimetals

Noblegases

Group

Relative atomicmassChemical symbol

Atomic number

Electronconfiguration

Percent (%) ofhuman body

all/mostorganisms

Macro element Traceelement

Metal

Semi-metal

Non-metal

Noble gas

Group

Perio

d

possibly

for some

Essential for...

Borongroup

Nitrogengroup

Carbongroup

Oxygengroup

A. Biologically important elements

B. Electron configurations: examples

Helium(He, Noble gas)1s2

Neon(Ne, Noble gas)1s2 2s2 2p6

Argon(Ar, Noble gas)1s2 2s2 2p6 3s2 3p6

1. Carbon (C)[He] 2s2 2p2

2. Chlorine (Cl)[Ne] 3s2 3p5

3. Iron (Fe)[Ar] 4s2 3d6

3Chemistry


Bonds

A. Orbital hybridization and chemicalbonding

Stable, covalent bonds between nonmetalatoms are produced when orbitals (see p. 2)of the two atoms form molecular orbitals thatare occupied by one electron from each of theatoms. Thus, the four bonding electrons of thecarbon atom occupy 2s and 2p atomic orbitals(1a). The 2s orbital is spherical in shape, whilethe three 2p orbitals are shaped like dumb-bells arranged along the x, y, and z axes. Itmight therefore be assumed that carbonatoms should form at least two different typesof molecular orbital. However, this is not nor-mally the case. The reason is an effect knownas orbital hybridization. Combination of the sorbital and the three p orbitals of carbon givesrise to four equivalent, tetrahedrally arrangedsp3 atomic orbitals (sp3 hybridization). Whenthese overlap with the 1s orbitals of H atoms,four equivalent -molecular orbitals (1b) areformed. For this reason, carbon is capable offorming four bondsi. e., it has a valency offour. Single bonds between nonmetal atomsarise in the same way as the four or singlebonds in methane (CH4). For example, thehydrogen phosphate ion (HPO4

2) and theammonium ion (NH4

+) are also tetrahedralin structure (1c).

A second common type of orbital hybrid-ization involves the 2s orbital and only two ofthe three 2p orbitals (2a). This process istherefore referred to as sp2 hybridization.The result is three equivalent sp2 hybrid orbi-tals lying in one plane at an angle of 120 toone another. The remaining 2px orbital is ori-ented perpendicular to this plane. In contrastto their sp3 counterparts, sp2-hybridizedatoms form two different types of bondwhen they combine into molecular orbitals(2b). The three sp2 orbitals enter into bonds,as described above. In addition, the electronsin the two 2px orbitals, known as S electrons,combine to give an additional, elongated molecular orbital, which is located aboveand below the plane of the bonds. Bondsof this type are called double bonds. Theyconsist of a bond and a bond, and ariseonly when both of the atoms involved arecapable of sp2 hybridization. In contrast tosingle bonds, double bonds are not freely ro-

tatable, since rotation would distort the -molecular orbital. This is why all of the atomslie in one plane (2c); in addition, cistransisomerism arises in such cases (see p. 8).Double bonds that are common in biomole-cules are C=C and C=O. C=N double bonds arefound in aldimines (Schiff bases, see p.178).

B. Resonance

Many molecules that have several doublebonds are much less reactive than might beexpected. The reason for this is that thedouble bonds in these structures cannot belocalized unequivocally. Their orbitals arenot confined to the space between the dou-ble-bonded atoms, but form a shared,extended S-molecular orbital. Structureswith this property are referred to as reso-nance hybrids, because it is impossible to de-scribe their actual bonding structure usingstandard formulas. One can either use whatare known as resonance structuresi. e.,idealized configurations in which electronsare assigned to specific atoms (cf. pp. 32 and66, for example)or one can use dashed linesas in Fig. B to suggest the extent of the delo-calized orbitals. (Details are discussed inchemistry textbooks.)

Resonance-stabilized systems include car-boxylate groups, as in formate; aliphatic hy-drocarbons with conjugated double bonds,such as 1,3-butadiene; and the systems knownas aromatic ring systems. The best-knownaromatic compound is benzene, which hassix delocalized electrons in its ring. Ex-tended resonance systems with 10 or more electrons absorb light within the visiblespectrum and are therefore colored. Thisgroup includes the aliphatic carotenoids (seep.132), for example, as well as the hemegroup, in which 18 electrons occupy an ex-tended molecular orbital (see p.106).

4 Basics


S Pz Py Px S Pz Py Px

C + 4 H CH4

1a 2a

1b

1c

2b

2c

H

CH

H

H

O

PO

O

OH NH

H

H

H C C

H

R

R'

H

C O

R'

R

C N

H

R

R'

HC

CC

CH

H

H

H

H

C

CC

C

CCH

H

H

H

H

H

H C

O

O

A. Orbital hybridization and chemical bonding

4 Equivalentsp3 atomicorbitals(tetrahedral)

3 Equivalentsp2 atomicorbitals(trigonal)

sp2Hybrid-ization

Bonding-molecularorbitals

sp3Hybrid-ization

1s Orbitalofhydro-genatom

sp3 Atomicorbitalsofcarbonatom

4 Bonding-molecularorbitals

5 Bonding-molecularorbitals

Formula

-Molecularorbitals

Formate 1,3-Butadiene Benzene

AldimineMethane Hydrogen phosphate AmmoniumIon

Alkene Carbonylcompound

B. Resonance

5Chemistry


Molecular structure

The physical and chemical behavior of mole-cules is largely determined by their constitu-tion (the type and number of the atoms theycontain and their bonding). Structural formu-las can therefore be used to predict not onlythe chemical reactivity of a molecule, but alsoits size and shape, and to some extent itsconformation (the spatial arrangement ofthe atoms). Some data providing the basisfor such predictions are summarized hereand on the facing page. In addition, L-dihy-droxyphenylalanine (L-dopa; see p. 352), isused as an example to show the way in whichmolecules are illustrated in this book.

A. Molecule illustrations

In traditional two-dimensional structuralformulas (A1), atoms are represented as lettersymbols and electron pairs are shown as lines.Lines between two atomic symbols symbolizetwo bonding electrons (see p. 4), and all of theother lines represent free electron pairs, suchas those that occur in O and N atoms. Freeelectrons are usually not represented explic-itly (and this is the convention used in thisbook as well). Dashed or continuous circles orarcs are used to emphasize delocalized elec-trons.

Ball-and-stick models (A2) are used to illus-trate the spatial structure of molecules. Atomsare represented as colored balls (for the colorcoding, see the inside front cover) and bonds(including multiple bonds) as gray cylinders.Although the relative bond lengths and anglescorrespond to actual conditions, the size atwhich the atoms are represented is too smallto make the model more comprehensible.

Space-filling van der Waals models (A3) areuseful for illustrating the actual shape andsize of molecules. These models representatoms as truncated balls. Their effective ex-tent is determined by what is known as thevan der Waals radius. This is calculated fromthe energetically most favorable distance be-tween atoms that are not chemically bondedto one another.

B. Bond lengths and angles

Atomic radii and distances are now usuallyexpressed in picometers (pm; 1 pm =1012 m). The old angstrom unit (, = 100 pm) is now obsolete. The length ofsingle bonds approximately corresponds tothe sum of what are known as the covalentradii of the atoms involved (see inside frontcover). Double bonds are around 1020%shorter than single bonds. In sp3-hybridizedatoms, the angle between the individualbonds is approx. 110; in sp2-hybridizedatoms it is approx. 120.

C. Bond polarity

Depending on the position of the element inthe periodic table (see p. 2), atoms havedifferent electronegativityi. e., a differenttendency to take up extra electrons. The val-ues given in C2 are on a scale between 2 and 4.The higher the value, the more electronega-tive the atom. When two atoms with verydifferent electronegativities are bound toone another, the bonding electrons are drawntoward the more electronegative atom, andthe bond is polarized. The atoms involvedthen carry positive or negative partialcharges. In C1, the van der Waals surface iscolored according to the different charge con-ditions (red = negative, blue = positive). Oxy-gen is the most strongly electronegative of thebiochemically important elements, with C=Odouble bonds being especially highly polar.

D. Hydrogen bonds

The hydrogen bond, a special type of nonco-valent bond, is extremely important in bio-chemistry. In this type of bond, hydrogenatoms of OH, NH, or SH groups (known ashydrogen bond donors) interact with freeelectrons of acceptor atoms (for example, O,N, or S). The bonding energies of hydrogenbonds (1040 kJ mol1) are much lowerthan those of covalent bonds (approx.400 kJ mol1). However, as hydrogen bondscan be very numerous in proteins and DNA,they play a key role in the stabilization ofthese molecules (see pp. 68, 84). The impor-tance of hydrogen bonds for the properties ofwater is discussed on p. 26.

6 Basics


0.9 2.1 2.5 3.0 3.5 4.0

1 2 3 4

H C N O FNa

A H B A H B A H B

120

120

120

120120

110

110 110

110 110

110

108

124pm

111

pm14

9pm

110pm

95pm

154 pm

140 pm

137 pm

100 pm

270280 pm

280 pm

290 pm

290 pm

O

C

O

C C

N

H H

H

H O

O

HH

H

H

H

HH

OH H

O O

H

H H

H

C

CH

N

N

O

H

H

R1

H

O

N

CHC

C O

R2

C C

CN C

N

NHC

NR

H

N

H

H

H NC N

CH

CCO CH3

RO

Chiral center

1. Formula illustration

2. Ball- and-stick model

3. Van der Waals model

1. Partial charges in L-dopa

2. Electronegativities

C. Bond polarity

B. Bond lengths and anglesA. Molecule illustrations

D. Hydrogen bonds

Increasing electronegativity

Positive Neutral Negative

Acid Base

Initial state

1. Principle

Donor Acceptor

Hydrogen bond

Dissociatedacid

Protonatedbase

Complete reaction

Water Proteins DNA2. Examples

7Chemistry


Isomerism

Isomers are molecules with the same compo-sition (i. e. the same molecular formula), butwith different chemical and physical proper-ties. If isomers differ in the way in which theiratoms are bonded in the molecule, they aredescribed as structural isomers (cf. citric acidand isocitric acid, D). Other forms of isomer-ism are based on different arrangements ofthe substituents of bonds (A, B) or on thepresence of chiral centers in the molecule (C).

A. cistrans isomers

Double bonds are not freely rotatable (seep. 4). If double-bonded atoms have differentsubstituents, there are two possible orienta-tions for these groups. In fumaric acid, anintermediate of the tricarboxylic acid cycle(see p.136), the carboxy groups lie on differentsides of the double bond (trans or E position).In its isomer maleic acid, which is not pro-duced in metabolic processes, the carboxygroups lie on the same side of the bond (cisor Z position). Cistrans isomers (geometricisomers) have different chemical and physicalpropertiese. g., their melting points (Fp.)and pKa values. They can only be intercon-verted by chemical reactions.

In lipid metabolism, cistrans isomerism isparticularly important. For example, doublebonds in natural fatty acids (see p. 48) usuallyhave a cis configuration. By contrast, unsatu-rated intermediates of oxidation have atrans configuration. This makes the break-down of unsaturated fatty acids more compli-cated (see p.166). Light-induced cistrans iso-merization of retinal is of central importancein the visual cycle (see p. 358).

B. Conformation

Molecular forms that arise as a result of rota-tion around freely rotatable bonds are knownas conformers. Even small molecules can havedifferent conformations in solution. In thetwo conformations of succinic acid illustratedopposite, the atoms are arranged in a similarway to fumaric acid and maleic acid. Bothforms are possible, although conformation 1is more favorable due to the greater distancebetween the COOH groups and therefore oc-curs more frequently. Biologically active mac-

romolecules such as proteins or nucleic acidsusually have well-defined (native) confor-mations, which are stabilized by interactionsin the molecule (see p. 74).

C. Optical isomers

Another type of isomerism arises when a mol-ecule contains a chiral center or is chiral as awhole. Chirality (from the Greek cheir, hand)leads to the appearance of structures thatbehave like image and mirror-image andthat cannot be superimposed (mirror iso-mers). The most frequent cause of chiral be-havior is the presence of an asymmetric Catomi. e., an atom with four different sub-stituents. Then there are two forms (enan-tiomers) with different configurations. Usu-ally, the two enantiomers of a molecule aredesignated as L and D forms. Clear classifica-tion of the configuration is made possible bythe R/S system (see chemistry textbooks).

Enantiomers have very similar chemicalproperties, but they rotate polarized light inopposite directions (optical activity, seepp. 36, 58). The same applies to the enantiom-ers of lactic acid. The dextrorotatory L-lacticacid occurs in animal muscle and blood, whilethe D form produced by microorganisms isfound in milk products, for example (seep.148). The Fischer projection is often usedto represent the formulas for chiral centers(cf. p. 58).

D. The aconitase reaction

Enzymes usually function stereospecifically. Inchiral substrates, they only accept one of theenantiomers, and the reaction products areusually also sterically uniform. Aconitatehydratase (aconitase) catalyzes the conver-sion of citric acid into the constitution isomerisocitric acid (see p.136). Although citric acidis not chiral, aconitase only forms one of thefour possible isomeric forms of isocitric acid(2R,3S-isocitric acid). The intermediate of thereaction, the unsaturated tricarboxylic acidaconitate, only occurs in the cis form in thereaction. The trans form of aconitate is foundas a constituent of certain plants.

8 Basics


HO

H

COO

CH3C

HO

H

COO

CH3C

53 C

3.7

-2.5

53 C

3.7

+ 2.5

2

3

1

1 1

H2O H2OC

C

OOC H

OOC CH2 COO

COO

C

C

H OH

H2C

OOC H

COO

COO

C

C

H H

H2C

OOC OH

COO

COO

C

CH3

HO H

OOC

C

CH3

H HO

D. The aconitase reaction

Citrate (prochiral) cis-Aconitate (intermediate product) (2R,3S)-Isocitrate

Aconitase 4.2.1.3trans-Aconitate occurs in plants

A. cistrans isomers

C. Optical isomers

B. Conformers

Succinic acidConformation 1

SuccinicacidConformation 2

Fumaric acidFp. 287 CpKa 3.0, 4.5

Maleic acidFp. 130 CpKa 1.9, 6.5

Not rotatable Freely rotatable

Fischer projections

D-lactic acid

Fp.

pKa value

Specificrotation

L-lactic acid

Fp.

pKa value

Specificrotation In muscle, blood In milk products

L(S) D(R)

9Chemistry


Biomolecules I

A. Important classes of compounds

Most biomolecules are derivatives of simplecompounds of the non-metals oxygen (O),hydrogen (H), nitrogen (N), sulfur (S), andphosphorus (P). The biochemically importantoxygen, nitrogen, and sulfur compounds canbe formally derived from their compoundswith hydrogen (i. e., H2O, NH3, and H2S). Inbiological systems, phosphorus is found al-most exclusively in derivatives of phosphoricacid, H3PO4.

If one or more of the hydrogen atoms of anon-metal hydride are replaced formally withanother group, Re. g., alkyl residuesthenderived compounds of the type R-XHn1,R-XHn2-R, etc., are obtained. In this way,alcohols (R-OH) and ethers (R-O-R) are de-rived from water (H2O); primary amines (R-NH2), secondary amines (R-NH-R) and terti-ary amines (R-N-RR) amines are obtainedfrom ammonia (NH3); and thiols (R-SH) andthioethers (R-S-R) arise from hydrogen sul-fide (H2S). Polar groups such as -OH and -NH2are found as substituents in many organiccompounds. As such groups are much morereactive than the hydrocarbon structures towhich they are attached, they are referred toas functional groups.

New functional groups can arise as a resultof oxidation of the compounds mentionedabove. For example, the oxidation of a thiolyields a disulfide (R-S-S-R). Double oxidationof a primary alcohol (R-CH2-OH) gives riseinitially to an aldehyde (R-C(O)-H), and thento a carboxylic acid (R-C(O)-OH). In contrast,the oxidation of a secondary alcohol yields aketone (R-C(O)-R). The carbonyl group (C=O)is characteristic of aldehydes and ketones.

The addition of an amine to the carbonylgroup of an aldehyde yieldsafter removal ofwateran aldimine (not shown; see p.178).Aldimines are intermediates in amino acidmetabolism (see p.178) and serve to bondaldehydes to amino groups in proteins (seep. 62, for example). The addition of an alcoholto the carbonyl group of an aldehyde yields ahemiacetal (R-O-C(H)OH-R). The cyclic formsof sugars are well-known examples of hemi-

acetals (see p. 36). The oxidation of hemiace-tals produces carboxylic acid esters.

Very important compounds are the carbox-ylic acids and their derivatives, which can beformally obtained by exchanging the OHgroup for another group. In fact, derivativesof this type are formed by nucleophilic sub-stitutions of activated intermediate com-pounds and the release of water (see p.14).Carboxylic acid esters (R-O-CO-R) arise fromcarboxylic acids and alcohols. This group in-cludes the fats, for example (see p. 48). Sim-ilarly, a carboxylic acid and a thiol yield athioester (R-S-CO-R). Thioesters play an ex-tremely important role in carboxylic acid me-tabolism. The best-known compound of thistype is acetyl-coenzyme A (see p.12).

Carboxylic acids and primary amines reactto form carboxylic acid amides (R-NH-CO-R).The amino acid constituents of peptides andproteins are linked by carboxylic acid amidebonds, which are therefore also known aspeptide bonds (see p. 66).

Phosphoric acid, H3PO4, is a tribasic (three-protic) acidi. e., it contains three hydroxylgroups able to donate H+ ions. At least oneof these three groups is fully dissociatedunder normal physiological conditions, whilethe other two can react with alcohols. Theresulting products are phosphoric acid mono-esters (R-O-P(O)O-OH) and diesters (R-O-P(O)O-O-R). Phosphoric acid monoesters arefound in carbohydrate metabolism, for exam-ple (see p. 36), whereas phosphoric aciddiester bonds occur in phospholipids (seep. 50) and nucleic acids (see p. 82 ).

Compounds of one acid with another arereferred to as acid anhydrides. A particularlylarge amount of energy is required for theformation of an acidanhydride bond. Phos-phoric anhydride bonds therefore play a cen-tral role in the storage and release of chemicalenergy in the cell (see p.122). Mixed anhy-drides between carboxylic acids and phos-phoric acid are also very important energy-rich metabolites in cellular metabolism.

10 Basics


O N

SP

HO

H

OH

CR

H

R'

RO

R'

O

CR R'

O

CH R'

O

PO

O

OR

H

OH

CO

H

R'R

O

CO R'

H

O

CO R'

R

O

PO

O

OH

H

O

PO

O

OR

C R'

O

O

PO

O

OR

P O

O

OH

N

H

R H

N

R''

R R'N

H

R R'

RN

CR'

H

O

SH H

SR H

SR

SR'

O

CS R'

R

N

H

H H

A. Important classes of compounds

HemiacetalCarboxylic acid amide

Phosphoricacid ester

Thioester

energy-rich bond

Water

Primaryalcohol

Ether

Oxygen

Secondaryalcohol

Amino group

Nitrogen

Primaryamine

Ammonia

Tertiaryamine

Secondaryamine

Thiol

Disulfide

Sulfur

Carboxylic acid ester

Dihydrogen phosphate

Ketone

Aldehyde

Carboxylic acid

Phosphoric acid anhydride

Mixed anhydride

Carbonyl group

Carboxyl group

Hydrogen sulfide

Sulfhydrylgroup

Phosphorus

Oxidation

Oxidation

OxidationO

H

CH

H

R'

11Chemistry


Biomolecules II

Many biomolecules are made up of smallerunits in a modular fashion, and they can bebroken down into these units again. The con-struction of these molecules usually takesplace through condensation reactions involv-ing the removal of water. Conversely, theirbreakdown functions in a hydrolytic fash-ioni. e., as a result of water uptake. Thepage opposite illustrates this modular princi-ple using the example of an important coen-zyme.

A. Acetyl CoA

Coenzyme A (see also p.106) is a nucleotidewith a complex structure (see p. 80). It servesto activate residues of carboxylic acids (acylresidues). Bonding of the carboxy group of thecarboxylic acid with the thiol group of thecoenzyme creates a thioester bond (-S-CO-R;see p.10) in which the acyl residue has a highchemical potential. It can therefore be trans-ferred to other molecules in exergonic reac-tions. This fact plays an important role in lipidmetabolism in particular (see pp.162ff.), aswell as in two reactions of the tricarboxylicacid cycle (see p.136).

As discussed on p.16, the group transferpotential can be expressed quantitatively asthe change in free enthalpy (G) during hy-drolysis of the compound concerned. This isan arbitrary determination, but it providesimportant indications of the chemical energystored in such a group. In the case of acetyl-CoA, the reaction to be considered is:

Acetyl CoA + H2O acetate + CoA

In standard conditions and at pH 7, thechange in the chemical potential G (G0, seep.18) in this reaction amounts to 32 kJ mol1 and it is therefore as high as the G0of ATP hydrolysis (see p.18). In addition to theenergy-rich thioester bond, acetyl-CoA alsohas seven other hydrolyzable bonds with dif-ferent degrees of stability. These bonds, andthe fragments that arise when they are hydro-lyzed, will be discussed here in sequence.

(1) The reactive thiol group of coenzyme Ais located in the part of the molecule that isderived from cysteamine. Cysteamine is a bio-

genic amine (see p. 62) formed by decarbox-ylation of the amino acid cysteine.

(2) The amino group of cysteamine isbound to the carboxy group of another bio-genic amine via an acid amide bond (-CO-NH-). -Alanine arises through decarboxyla-tion of the amino acid aspartate, but it canalso be formed by breakdown of pyrimidinebases (see p.186).

(3) Another acid amide bond (-CO-NH-)creates the compound for the nextconstituent, pantoinate. This compound con-tains a chiral center and can therefore appearin two enantiomeric forms (see p. 8). In natu-ral coenzyme A, only one of the two forms isfound, the (R)-pantoinate. Human metabo-lism is not capable of producing pantoinateitself, and it therefore has to take up acompound of -alanine and pantoinatepantothenate (pantothenic acid)in theform of a vitamin in food (see p. 366).

(4) The hydroxy group at C-4 of pantoinateis bound to a phosphate residue by an esterbond.

The section of the molecule discussed sofar represents a functional unit. In the cell, it isproduced from pantothenate. The moleculealso occurs in a protein-bound form as 4-phosphopantetheine in the enzyme fattyacid synthase (see p.168). In coenzyme A,however, it is bound to 3,5-adenosine di-phosphate.

(5) When two phosphate residues bond,they do not form an ester, but an energy-rich phosphoric acid anhydride bond, asalso occurs in other nucleoside phosphates.By contrast, (6) and (7) are ester bonds again.

(8) The base adenine is bound to C-1 ofribose by an N-glycosidic bond (see p. 36). Inaddition to C-2 to C-4, C-1 of ribose also rep-resents a chiral center. The E-configuration isusually found in nucleotides.

12 Basics


C H 3

C

S

O

C H 2

C H 2

N

C

C H 2

H

O

C H 2

NH

C

C

O

H OH

C

C H 2

C H 3H 3C

O

P

O

OO

P

O

OO

C H 2

O

H

H H

O OH

H

N

NN

HC

N

N H 2

P

O

OO

Ribose

A. Acetyl CoA

Acetate

Cysteamine

-Alanine

Pantoinate

Phosphate

Phosphate

Phosphate

Thioester bond

Acidamidebond

Phosphoric acidester bond

Phosphoric acidanhydride bond

Van der Waals model

Adenine

Energy-rich bond

Chiral centers

Acidamide bond



N-glycosidic bond

13Chemistry


Chemical reactions

Chemical reactions are processes in whichelectrons or groups of atoms are taken upinto molecules, exchanged between mole-cules, or shifted within molecules. Illustratedhere are the most important types of reactionin organic chemistry, using simple examples.Electron shifts are indicated by red arrows.

A. Redox reactions

In redox reactions (see also p. 32), electronsare transferred from one molecule (the reduc-ing agent) to another (the oxidizing agent).One or two protons are often also transferredin the process, but the decisive criterion forthe presence of a redox reaction is the elec-tron transfer. The reducing agent is oxidizedduring the reaction, and the oxidizing agent isreduced.

Fig. A shows the oxidation of an alcoholinto an aldehyde (1) and the reduction ofthe aldehyde to alcohol (2). In the process,one hydride ion is transferred (two electronsand one proton; see p. 32), which moves tothe oxidizing agent A in reaction 1. The super-fluous proton is bound by the catalytic effectof a base B. In the reduction of the aldehyde(2), A-H serves as the reducing agent and theacid H-B is involved as the catalyst.

B. Acidbase reactions

In contrast to redox reactions, only protontransfer takes place in acidbase reactions(see also p. 30). When an acid dissociates (1),water serves as a proton acceptor (i. e., as abase). Conversely, water has the function ofan acid in the protonation of a carboxylateanion (2).

C. Additions/eliminations

A reaction in which atoms or molecules aretaken up by a multiple bond is described asaddition. The converse of additioni. e., theremoval of groups with the formation of adouble bond, is termed elimination. Whenwater is added to an alkene (1a), a proton isfirst transferred to the alkene. The unstablecarbenium cation that occurs as an intermedi-ate initially takes up water (not shown), be-fore the separation of a proton produces alco-

hol (1b). The elimination of water from thealcohol (2, dehydration) is also catalyzed byan acid and passes via the same intermediateas the addition reaction.

D. Nucleophilic substitutions

A reaction in which one functional group (seep.10) is replaced by another is termed substi-tution. Depending on the process involved, adistinction is made between nucleophilic andelectrophilic substitution reactions (seechemistry textbooks). Nucleophilic substitu-tions start with the addition of one moleculeto another, followed by elimination of the so-called leaving group.

The hydrolysis of an ester to alcohol andacid (1) and the esterification of a carboxylicacid with an alcohol (2) are shown here as anexample of the SN2 mechanism. Both reac-tions are made easier by the marked polarityof the C=O double bond. In the form of esterhydrolysis shown here, a proton is removedfrom a water molecule by the catalytic effectof the base B. The resulting strongly nucleo-philic OH ion attacks the positively chargedcarbonyl C of the ester (1a), and an unstablesp3-hybridized transition state is produced.From this, either water is eliminated (2b)and the ester re-forms, or the alcohol ROH iseliminated (1b) and the free acid results. Inesterification (2), the same steps take place inreverse.

Further information

In rearrangements (isomerizations, notshown), groups are shifted within one andthe same molecule. Examples of this in bio-chemistry include the isomerization of sugarphosphates (see p. 36) and of methylmalonyl-CoA to succinyl CoA (see p.166).

14 Basics


H B

R C O

O

OR'

H

O C

R' O

RB

B

HO

H

HO

H

BH

BH

R C O

O

OR'

H

R C

O

O H

H B

R C O

O

OR'

H

B

R C

O

O H

R' O

H

OH

H

R C

O

O H

R C

O

O H

H

OH

H

OHH

O HH

O H

H

O H

R C

O

O

R C

O

O

R C

O

O

H BBA A

H

H BBA H

A

OB

C

H

R

H

HA

R C

O

H

OC

H

R

H

H

R C

O

H

H BH

A

O C

R' O

R

HO

HB1a 1b

1a

2b

2b 2a

C C

R'

H

H

R

R C C

H

R'

H

H

B

B

HO

H

HO

H

BH

BH

R C C

H

R'

H

HOH

BH

BH

B

B

2b

1a

2a

1b

2

1

2

1

2

1

2

1

B R' O

H

BH

BR' O

HBH

1b

2a

B. Acidbase reactionsA. Redox reactions

C. Additions/eliminations

AlcoholCarbonium ion

Acid

Anion

Alcohol Aldehyde

D. Nucleophilic substitutions

Transitional state Carboxylicacid

Alcohol

Alcohol

Alkene

Ester

15Chemistry


Energetics

To obtain a better understanding of the pro-cesses involved in energy storage and conver-sion in living cells, it may be useful first torecall the physical basis for these processes.

A. Forms of work

There is essentially no difference betweenwork and energy. Both are measured in joule(J = 1 N m). An outdated unit is the calorie(1 cal = 4.187 J). Energy is defined as the abil-ity of a system to perform work. There aremany different forms of energye. g., me-chanical, chemical, and radiation energy.

A system is capable of performing workwhen matter is moving along a potential gra-dient. This abstract definition is best under-stood by an example involving mechanicalwork (A1). Due to the earths gravitationalpull, the mechanical potential energy of anobject is the greater the further the object isaway from the center of the earth. A potentialdifference (P) therefore exists between ahigher location and a lower one. In a waterfall,the water spontaneously follows this poten-tial gradient and, in doing so, is able to per-form worke. g., turning a mill.

Work and energy consist of two quantities:an intensity factor, which is a measure of thepotential differencei. e., the driving forceof the process(here it is the height differ-ence) and a capacity factor, which is a mea-sure of the quantity of the substance beingtransported (here it is the weight of thewater). In the case of electrical work (A2),the intensity factor is the voltagei. e., theelectrical potential difference between thesource of the electrical current and theground, while the capacity factor is theamount of charge that is flowing.

Chemical work and chemical energy aredefined in an analogous way. The intensityfactor here is the chemical potential of a mol-ecule or combination of molecules. This isstated as free enthalpy G (also known asGibbs free energy). When molecules spon-taneously react with one another, the result isproducts at lower potential. The difference inthe chemical potentials of the educts andproducts (the change in free enthalpy, 'G) isa measure of the driving force of the reac-tion. The capacity factor in chemical work is

the amount of matter reacting (in mol).Although absolute values for free enthalpy Gcannot be determined, G can be calculatedfrom the equilibrium constant of the reaction(see p.18).

B. Energetics and the course of processes

Everyday experience shows that water neverflows uphill spontaneously. Whether a partic-ular process can occur spontaneously or notdepends on whether the potential differencebetween the final and the initial state, P =P2 P1, is positive or negative. If P2 is smallerthan P1, then P will be negative, and theprocess will take place and perform work.Processes of this type are called exergonic(B1). If there is no potential difference, thenthe system is in equilibrium (B2). In the case ofendergonic processes, P is positive (B3).Processes of this type do not proceed sponta-neously.

Forcing endergonic processes to take placerequires the use of the principle of energeticcoupling. This effect can be illustrated by amechanical analogy (B4). When two massesM1 and M2 are connected by a rope, M1 willmove upward even though this part of theprocess is endergonic. The sum of the twopotential differences (Peff = P1 + P2) isthe determining factor in coupled processes.When Peff is negative, the entire process canproceed.

Energetic coupling makes it possible toconvert different forms of work and energyinto one another. For example, in a flashlight,an exergonic chemical reaction provides anelectrical voltage that can then be used forthe endergonic generation of light energy. Inthe luminescent organs of various animals, itis a chemical reaction that produces the light.In the musculature (see p. 336), chemical en-ergy is converted into mechanical work andheat energy. A form of storage for chemicalenergy that is used in all forms of life is aden-osine triphosphate (ATP; see p.122). Ender-gonic processes are usually driven by cou-pling to the strongly exergonic breakdownof ATP (see p.122).

16 Basics


J = Joule = N m =1 kg m2 s-2, 1 cal = 4.187 J

P

P1

P2

M1 M2

P3

P1

P2

P3

P1

P2

Peff

P

A. Forms of work

Pote

ntia

lLo

wer

Hig

her Elevated position

Lower position

1. Mechanical work 3. Chemical work

Weight

Vol

tage

Ground

Charge

Voltagesource

2. Electrical work

Quantity

Products

Educts

Cha

nge

in fr

ee e

nerg

y (

G)

Hei

ght

P < 0

Potential

1. Exergonic

P = 0 P > 0 Peff < 0

Potential

2. Equilibrium 3. Endergonic 4. Energetically coupled

Coupled processes canoccur spontaneously

Form of work

Mechanical

Electrical

Chemical

Intensity factor

Height

Voltage

Free-enthalpychange G

Unit

m

V =J C -1

J mol -1

Unit

J m -1

C

mol

Work =

Height Weight

Voltage Charge

G Quantity

Unit

J

J

J

Capacity factor

Weight

Charge

Quantity

B. Energetics and the course of processes

Process occursspontaneously

Process cannotoccur

17Physical Chemistry


Equilibriums

A. Group transfer reactions

Every chemical reaction reaches after a time astate of equilibrium in which the forward andback reactions proceed at the same speed. Thelaw of mass action describes the concentra-tions of the educts (A, B) and products (C, D) inequilibrium. The equilibrium constant K is di-rectly related to G0, the change in freeenthalpy G involved in the reaction (seep.16) under standard conditions (G0 = R T ln K). For any given concentrations, thelower equation applies. At G < 0, the reac-tion proceeds spontaneously for as long as ittakes for equilibrium to be reached (i. e., untilG = 0). At G > 0, a spontaneous reaction isno longer possible (endergonic case; seep.16). In biochemistry, G is usually relatedto pH 7, and this is indicated by the primesymbol (G0 or G).

As examples, we can look at two grouptransfer reactions (on the right). In ATP (seep.122), the terminal phosphate residue is at ahigh chemical potential. Its transfer to water(reaction a, below) is therefore strongly exer-gonic. The equilibrium of the reaction(G = 0; see p.122) is only reached whenmore than 99.9% of the originally availableATP has been hydrolyzed. ATP and similarcompounds have a high group transferpotential for phosphate residues. Quantita-tively, this is expressed as the 'G of hydrolysis(G0 = 32 kJ mol1; see p.122).

In contrast, the endergonic transfer of am-monia (NH3) to glutamate (Glu, reaction b,G0 = +14 kJ mol1) reaches equilibrium soquickly that only minimal amounts of theproduct glutamine (Gln) can be formed inthis way. The synthesis of glutamine fromthese preliminary stages is only possiblethrough energetic coupling (see pp.16, 124).

B. Redox reactions

The course of electron transfer reactions (re-dox reactions, see p.14) also follows the law ofmass action. For a single redox system (seep. 32), the Nernst equation applies (top). Theelectron transfer potential of a redox system(i. e., its tendency to give off or take up elec-trons) is given by its redox potential E (instandard conditions, E0 or E0). The lower the

redox potential of a system is, the higher thechemical potential of the transferred elec-trons. To describe reactions between two re-dox systems, the difference between thetwo systems redox potentialsis usuallyused instead of G. G and E have a simplerelationship, but opposite signs (below). Aredox reaction proceeds spontaneouslywhen E > 0, i. e. G < 0.

The right side of the illustration shows theway in which the redox potential E is depen-dent on the composition (the proportion ofthe reduced form as a %) in two biochemicallyimportant redox systems (pyruvate/lactateand NAD+/NADH+H+; see pp. 98, 104). In thestandard state (both systems reduced to 50%),electron transfer from lactate to NAD+ is notpossible, because E is negative (E = 0.13 V,red arrow). By contrast, transfer can proceedsuccessfully if the pyruvate/lactate system isreduced to 98% and NAD+/NADH is 98% oxi-dized (green arrow, E = +0.08 V).

C. Acidbase reactions

Pairs of conjugated acids and bases are alwaysinvolved in proton exchange reactions (seep. 30). The dissociation state of an acidbasepair depends on the H+ concentration. Usu-ally, it is not this concentration itself that isexpressed, but its negative decadic logarithm,the pH value. The connection between the pHvalue and the dissociation state is describedby the HendersonHasselbalch equation (be-low). As a measure of the proton transferpotential of an acidbase pair, its pKa valueis usedthe negative logarithm of the acidconstant Ka (where a stands for acid).

The stronger an acid is, the lower its pKavalue. The acid of the pair with the lower pKavalue (the stronger acidin this case aceticacid, CH3COOH) can protonate (green arrow)the base of the pair with the higher pKa (inthis case NH3), while ammonium acetate(NH4

+ and CH3COO) only forms very little

CH3COOH and NH3.

18 Basics


A + B C + D

K=

Ared Aox

a

b

HA + H2O

pH a

b

30

20

10

0

-10

-20

-30

-40

-500 20 40 60 80 100

G = - R T ln K

[C] [D]

[A] [B]

[C] [D]

[A] [B]

R = 8.314 J mol -1 K-1

G = G + R T ln

G = n F EE = EAcceptor EDonor

E = E + lnR Tn F

[Box] [Bred]

[Ared] [Aox]

A + H3O

pH = pKa + log[HA]

[A ]

G(a)

G(b)

E (a)

E (b)

NAD /NADH+H

- 0.5

- 0.4

- 0.3

-0.2

- 0.1

0.0

0 20 40 60 80 100

pKa(a)

pKa(b)

NH4 /NH3

0

2

4

6

8

10

12

14

0 20 40 60 80 100

CH3 COOH/CH3COO

Glu + NH4 Gln + H2O

ATP + H2O ADP + Pi

E = E + lnR Tn F [Ared]

[Aox]

K =[HA] [H2O]

[A ] [H3O ]

Ka=[HA]

[A ] [H ]

n = No. of electrons transferredF = Faraday constant

A. Group transfer reactions

Reaction

Law ofmass action

Only appliesin chemicalequilibrium

RelationshipbetweenG0 and K

In any conditions

G

(KJ/

mol

)

% converted

Equilibrium constantEqui-librium

Equi-librium

Measure of group transfer potential

B. Redox reactions

For a redoxsystem

For any redoxreaction

Redo

x po

tent

ial E

(V)

% reduced

Pyruvate/lactate

Standardreaction

Law of massaction

Simplified

HendersonHasselbalchequation

Definitionand sizes

% dissociated

C. Acidbase reactions

Measure of proton transfer potential

Measure of electron transfer potential



Enthalpy and entropy

The change in the free enthalpy of a chemicalreaction (i. e., its G) depends on a number offactorse. g., the concentrations of the reac-tants and the temperature (see p.18). Twofurther factors associated with molecularchanges occurring during the reaction are dis-cussed here.

A. Heat of reaction and calorimetry

All chemical reactions involve heat exchange.Reactions that release heat are calledexothermic, and those that consume heatare called endothermic. Heat exchange ismeasured as the enthalpy change H (theheat of reaction). This corresponds to theheat exchange at constant pressure. In exo-thermic reactions, the system loses heat, andH is negative. When the reaction is endo-thermic, the system gains heat, and H be-comes positive.

In many reactions, H and G are similar inmagnitude (see B1, for example). This fact isused to estimate the caloric content of foods.In living organisms, nutrients are usually oxi-dized by oxygen to CO2 and H2O (see p.112).The maximum amount of chemical work sup-plied by a particular foodstuff (i. e., the G forthe oxidation of the utilizable constituents)can be estimated by burning a weighedamount in a calorimeter in an oxygen atmo-sphere. The heat of the reaction increases thewater temperature in the calorimeter. Thereaction heat can then be calculated fromthe temperature difference T.

B. Enthalpy and entropy

The reaction enthalpy H and the change infree enthalpy G are not always of the samemagnitude. There are even reactions that oc-cur spontaneously (G < 0) even though theyare endothermic (H > 0). The reason for thisis that changes in the degree of order of thesystem also strongly affect the progress of areaction. This change is measured as the en-tropy change ('S).

Entropy is a physical value that describesthe degree of order of a system. The lower thedegree of order, the larger the entropy. Thus,when a process leads to increase in disor-derand everyday experience shows that

this is the normal state of affairsS is pos-itive for this process. An increase in the orderin a system (S < 0) always requires an inputof energy. Both of these statements areconsequences of an important natural law,the Second Law of Thermodynamics. Theconnection between changes in enthalpyand entropy is described quantitatively bythe GibbsHelmholtz equation (G = H T S). The following examples will helpexplain these relationships.

In the knall-gas (oxyhydrogen) reaction(1), gaseous oxygen and gaseous hydrogenreact to form liquid water. Like many redoxreactions, this reaction is strongly exothermic(i. e., H < 0). However, during the reaction,the degree of order increases. The total num-ber of molecules is reduced by one-third, anda more highly ordered liquid is formed fromfreely moving gas molecules. As a result of theincrease in the degree of order (S < 0), theterm T S becomes positive. However, thisis more than compensated for by the decreasein enthalpy, and the reaction is still stronglyexergonic (G < 0).

The dissolution of salt in water (2) is endo-thermic (H > 0)i. e., the liquid cools. Never-theless, the process still occurs spontane-ously, since the degree of order in thesystem decreases. The Na+ and Cl ions areinitially rigidly fixed in a crystal lattice. Insolution, they move about independentlyand in random directions through the fluid.The decrease in order (S > 0) leads to anegative T S term, which compensatesfor the positive H term and results in anegative G term overall. Processes of thistype are described as being entropy-driven.The folding of proteins (see p. 74) and theformation of ordered lipid structures in water(see p. 28) are also mainly entropy-driven.

20 Basics


12

3

4

5

6

1

2

3

4

5

6

H = - 287 kJ mol -1

G = - 238 kJ mol -1

-T S = +49 kJ mol -1 -T S = - 12.8 kJ mol -1

G = - 9.0 kJ mol -1

H = +3.8 kJ mol -1

O2

1

2

3

4

5

6

1

2

3

4

5

6

CO2

-200 -100 0 +100 +200 -12 -8 -4 0 +4 +8 +12

G = H - T S

H2O

A. Heat of reaction and calorimetry

1. Knall-gas reaction 2. Dissolution of NaCl in water

Low degreeof order

System re-leases heat,H 0

1 mol Na1 mol Cl

Systemabsorbsheat,H > 0(endothermic)

High degreeof order

Ignition wireto start the reaction

Thermometer

Temperatureinsulation

Pressurizedmetalcontainer

Water

Sample

Stirrer

Waterheated

An enthalpy of1kJ warms 1 l of waterby 0.24 C

Combustion

1 mol H2 1 mol NaCl(crystalline)

H: changeof enthalpy,heat exchange

S: change ofentropy, i.e.degree of order

Gibbs-Helmholtz equation

1/2 mol O2

B. Enthalpy and entropy

Water

Energy Energy



Reaction kinetics

The change in free enthalpy G in a reactionindicates whether or not the reaction can takeplace spontaneously in given conditions andhow much work it can perform (see p.18).However, it does not tell us anything aboutthe rate of the reactioni. e., its kinetics.

A. Activation energy

Most organic chemical reactions (with theexception of acidbase reactions) proceedonly very slowly, regardless of the valueof G. The reason for the slow reaction rateis that the molecules that reacttheeductshave to have a certain minimum en-ergy before they can enter the reaction. This isbest understood with the help of an energydiagram (1) of the simplest possible reactionA B. The educt A and the product B are eachat a specific chemical potential (Ge and Gp,respectively). The change in the free enthalpyof the reaction, G, corresponds to the differ-ence between these two potentials. To beconverted into B, A first has to overcome apotential energy barrier, the peak of which,Ga, lies well above Ge. The potential differenceGa Ge is the activation energy Ea of the re-action (in kJ mol1).

The fact that A can be converted into B at allis because the potential Ge only representsthe average potential of all the molecules.Individual molecules may occasionally reachmuch higher potentialse. g., due to collisionswith other molecules. When the increase inenergy thus gained is greater than Ea, thesemolecules can overcome the barrier and beconverted into B. The energy distribution for agroup of molecules of this type, as calculatedfrom a simple model, is shown in (2) and (3).n/n is the fraction of molecules that havereached or exceeded energy E (in kJ per mol).At 27 C, for example, approximately 10% ofthe molecules have energies > 6 kJ mol1.The typical activation energies of chemicalreactions are much higher. The course ofthe energy function at energies of around50 kJ mol1 is shown in (3). Statistically, at27 C only two out of 109 molecules reach thisenergy. At 37 C, the figure is already four.This is the basis for the long-familiar Q10lawa rule of thumb that states that thespeed of biological processes approximately

doubles with an increase in temperature of10 C.

B. Reaction rate

The velocity v of a chemical reaction is deter-mined experimentally by observing thechange in the concentration of an educt orproduct over time. In the example shown(again a reaction of the A B type), 3 mmolof the educt A is converted per second and3 mmol of the product B is formed per secondin one liter of the solution. This correspondsto a rate of

v = 3 mM s1 = 3 103 mol L1 s1

C. Reaction order

Reaction rates are influenced not only by theactivation energy and the temperature, butalso by the concentrations of the reactants.When there is only one educt, A (1), v isproportional to the concentration [A] of thissubstance, and a first-order reaction is in-volved. When two educts, A and B, reactwith one another (2), it is a second orderreaction (shown on the right). In this case,the rate v is proportional to the product ofthe educt concentrations (12 mM2 at thetop, 24 mM2 in the middle, and 36 mM2 atthe bottom). The proportionality factors k andk are the rate constants of the reaction. Theyare not dependent on the reaction concentra-tions, but depend on the external conditionsfor the reaction, such as temperature.

In B, only the kinetics of simple irreversiblereactions is shown. More complicated cases,such as reaction with three or more reversiblesteps, can usually be broken down into first-order or second-order partial reactions anddescribed using the corresponding equations(for an example, see the MichaelisMentenreaction, p. 92).

22 Basics


50 s 0 s 1 s

10

15

1

2

3

1

2

3

C1 s

1. 2.

0 s 1 s 3 s

1. 2. 3.

0.0 0.5 1.0 0 5 100

2

4

6

8

10 55

50

45

1. 2. 3.

[A] (mM)

A. Activation energy

B. Reaction rate

mM =mmol l-1

Product B

Substrate A

Chemicalpotential

Ener

gy (k

J m

ol-1

)

Activation energy

Ener

gy (k

J m

ol-1

)

First-order reaction Second-order reaction

1 Liter

k = 1/5 s -1 k' = 1/12 l mmol-1 s -1

k, k' : Rate constants

v (mM s-1) (mM) v (mM s-1)

v = k [A] v = k' [A] [B]

C. Reaction order

Ea

G = Gp - Ge

Ga - Ge=

14. color atlas of biochemistry, 2 nd ed (j koolman, k h roehm)(thieme,2005) - - - pretty good

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Transcript of 14. color atlas of biochemistry, 2 nd ed (j koolman, k h roehm)(thieme,2005) - - - pretty good