Color Atlas
`
`of Biochemistry
`
`Floxibfl-flk
`
`
`CU REVAC EX2027
`CUREVAC EX2027
`Page 1
`Page 1
`
`

`

`Color Atlas of
`Biochemistry
`Second edition, revised and enlarged
`
`Jan Koolman
`Professor
`Philipps University Marburg
`Institute of Physiologic Chemistry
`Marburg, Germany
`
`Klaus-Heinrich Roehm
`Professor
`Philipps University Marburg
`Institute of Physiologic Chemistry
`Marburg, Germany
`
`215 color plates by Juergen Wirth
`
`Thieme
`Stuttgart · New York
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
`CUREVAC EX2027
`Page 2
`
`

`

`IV
`
`Library of Congress Cataloging-in-
`Publication Data
`
`This book is an authorized and updated trans-
`lation of the 3rd German edition published
`and copyrighted 2003 by Georg Thieme Ver-
`lag, Stuttgart, Germany. Title of the German
`edition: Taschenatlas der Biochemie
`
`Illustrator: Juergen Wirth, Professor of Visual
`Communication, University of Applied Scien-
`ces, Darmstadt, Germany
`
`Translator: Michael Robertson, BA DPhil,
`Augsburg, Germany
`
`1st Dutch edition 2004
`1st English edition 1996
`1st French edition 1994
`2nd French edition 1999
`3rd French edition 2004
`1st German edition 1994
`2nd German edition 1997
`1st Greek edition 1999
`1st Indonesian edition 2002
`1st Italian edition 1997
`1st Japanese edition 1996
`1st Portuguese edition 2004
`1st Russian edition 2000
`1st Spanish edition 2004
`
`© 2005 Georg Thieme Verlag
`Rüdigerstrasse 14, 70469 Stuttgart,
`Germany
`http://www.thieme.de
`Thieme New York, 333 Seventh Avenue,
`New York, NY 10001 USA
`http://www.thieme.com
`
`Cover design: Cyclus, Stuttgart
`Cover drawing: CAP cAMP bound to DNA
`Typesetting by primustype Hurler GmbH,
`Notzingen
`Printed in Germany by Appl, Wemding
`
`ISBN 3-13-100372-3 (GTV)
`ISBN 1-58890-247-1 (TNY)
`
`Important note: Medicine is an ever-changing
`science undergoing continual development.
`Research and clinical experience are continu-
`ally expanding our knowledge, in particular
`our knowledge of proper treatment and drug
`therapy. Insofar as this book mentions any
`dosage or application, readers may rest as-
`sured that the authors, editors, and publishers
`have made every effort to ensure that such
`references are in accordance with the state of
`knowledge at the time of production of the
`book. Nevertheless, this does not involve, im-
`ply, or express any guarantee or responsibility
`on the part of the publishers in respect to any
`dosage instructions and forms of applications
`stated in the book. Every user is requested to
`examine carefully the manufacturers’ leaflets
`accompanying each drug and to check, if nec-
`essary in consultation with a physician or
`specialist, whether the dosage schedules
`mentioned therein or the contraindications
`stated by the manufacturers differ from the
`statements made in the present book. Such
`examination is particularly important with
`drugs that are either rarely used or have
`been newly released on the market. Every
`dosage schedule or every form of application
`used is entirely at the user’s own risk and
`responsibility. The authors and publishers re-
`quest every user to report to the publishers
`any discrepancies or inaccuracies noticed. If
`errors in this work are found after publication,
`errata will be posted at www.thieme.com on
`the product description page.
`
`Some of the product names, patents, and reg-
`istered designs referred to in this book are in
`fact registered trademarks or proprietary
`names even though specific reference to this
`fact is not always made in the text. Therefore,
`the appearance of a name without designa-
`tion as proprietary is not to be construed as a
`representation by the publisher that it is in
`the public domain.
`This book, including all parts thereof, is legally
`protected by copyright. Any use, exploitation,
`or commercialization outside the narrow lim-
`its set by copyright legislation, without the
`publisher’s consent, is illegal and liable to
`prosecution. This applies in particular to pho-
`tostat reproduction, copying, mimeograph-
`ing, preparation of microfilms, and electronic
`data processing and storage.
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
`CUREVAC EX2027
`Page 3
`
`

`

`About the Authors
`
`V
`
`Jan Koolman (left) was born in Lübeck, Ger-
`many, and grew up with the sea wind blowing
`off the Baltic. The high school he attended in
`the Hanseatic city of Lübeck was one that
`focused on providing a classical education,
`which left its mark on him. From 1963 to
`1969, he studied biochemistry at the Univer-
`sity of Tübingen. 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 began
`to study the biochemistry of insects and other
`invertebrates. He took his postdoctoral de-
`gree in 1977 in the field of human medicine,
`and was appointed Honorary Professor in
`1984. His field of study today is biochemical
`endocrinology. His other interests include ed-
`ucational methods in biochemistry. He is cur-
`rently Dean of Studies in the Department of
`Medicine in Marburg; he is married to an art
`teacher.
`Klaus-Heinrich Röhm (right) comes from
`Stuttgart, Germany. After graduating from
`the School of Protestant Theology in Urach
`—another institution specializing in classical
`studies—and following a period working in
`the field of physics, he took a diploma in bio-
`chemistry at the University of Tübingen,
`where the two authors first met. Since 1970,
`he has also worked in the Department of
`Medicine at the University of Marburg. He
`
`took his doctorate under the supervision of
`Friedhelm Schneider, and his postdoctoral de-
`gree in 1980 was in the Department of Chem-
`istry. He has been an Honorary Professor since
`1986. His research group is concerned with
`the structure and function of enzymes in-
`volved in amino acid metabolism. He is mar-
`ried to a biologist and has two children.
`Jürgen Wirth (center) studied in Berlin and at
`the 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, Jürgen Wirth was involved
`in designing the exhibition space in the
`Senckenberg Museum of Natural History in
`Frankfurt am Main, while at the same time
`working as a freelance associate with several
`publishing companies, providing illustrations
`for schoolbooks, non-fiction titles, and scien-
`tific publications. He has received several
`awards for book illustration and design. In
`1978, he was appointed to a professorship at
`the College of Design in Schwäbisch Gmünd,
`Germany, and in 1986 he became Professor of
`Design at the Academy of Design in Darm-
`stadt, Germany. His specialist fields include
`scientific graphics/information graphics and
`illustration methods. He is married and has
`three children.
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
`CUREVAC EX2027
`Page 4
`
`

`

`VI
`
`Preface
`
`Biochemistry is a dynamic, rapidly growing
`field, and the goal of this color atlas is to
`illustrate this fact visually. The precise boun-
`daries between biochemistry and related
`fields, such as cell biology, anatomy, physiol-
`ogy, genetics, and pharmacology, are dif cult
`to define and, in many cases, arbitrary. This
`overlap is not coincidental. The object being
`studied is often the same—a nerve cell or a
`mitochondrion, for example—and only the
`point 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 molecules
`has always been in the foreground. However,
`new aspects inherited from biochemistry’s
`other parent, the biological sciences, are
`now increasingly being added: the relation-
`ship between chemical structure and biolog-
`ical function, the pathways of information
`transfer, observance of the ways in which
`biomolecules 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 bound
`to become more and more important.
`Owing to space limitations, we have concen-
`trated here on the biochemistry of humans
`and mammals, although the biochemistry of
`other animals, plants, and microorganisms is
`no less interesting. In selecting the material
`for this book, we have put the emphasis on
`subjects relevant to students of human med-
`icine. The main purpose of the atlas is to serve
`as an overview and to provide visual informa-
`tion quickly and ef ciently. Referring to text-
`books can easily fill any gaps. For readers
`encountering biochemistry for the first time,
`some of the plates may look rather complex. It
`must be emphasized, therefore, that the atlas
`is 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. The
`graphics were designed conservatively, the
`aim being to avoid illustrations that might
`look too spectacular or exaggerated. Our
`goal was to achieve a visual and aesthetic
`way of representing scientific facts that would
`be simple and at the same time effective for
`teaching purposes. Use of graphics software
`helped to maintain consistency in the use of
`shapes, colors, dimensions, and labels, in par-
`ticular. Formulae and other repetitive ele-
`ments and structures could be handled easily
`and precisely with the assistance of the com-
`puter.
`Color-coding has been used throughout to aid
`the reader, and the key to this is given in two
`special color plates on the front and rear in-
`side covers. For example, in molecular models
`each of the more important atoms has a par-
`ticular color: gray for carbon, white for hydro-
`gen, blue for nitrogen, red for oxygen, and so
`on. The different classes of biomolecules are
`also distinguished by color: proteins are al-
`ways shown in brown tones, carbohydrates in
`violet, lipids in yellow, DNA in blue, and RNA
`in green. In addition, specific symbols are
`used for the important coenzymes, such as
`ATP and NAD+. The compartments in which
`biochemical processes take place are color-
`coded as well. For example, the cytoplasm is
`shown in yellow, while the extracellular space
`is 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 with
`anatomy and physiology. In this book, we
`sometimes 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 these
`cases, we have tried to be as realistic as pos-
`sible. The models of small molecules are
`based on conformations calculated by com-
`puter-based molecular modeling. In illustrat-
`ing macromolecules, we used structural infor-
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
`CUREVAC EX2027
`Page 5
`
`

`

`Preface
`
`VII
`
`We are grateful to many readers for their
`comments and valuable criticisms during the
`preparation of this book. Of course, we would
`also welcome further comments and sugges-
`tions from our readers.
`
`August 2004
`
`Jan Koolman,
`Klaus-Heinrich Röhm
`Marburg
`
`Jürgen Wirth
`Darmstadt
`
`mation obtained by X-ray crystallography
`that is stored in the Protein Data Bank. In
`naming enzymes, we have followed the of -
`cial nomenclature recommended by the
`IUBMB. For quick identification, EC numbers
`(in italics) are included with enzyme names.
`To help students assess the relevance of the
`material (while preparing for an examination,
`for example), we have included symbols on
`the text pages next to the section headings to
`indicate how important each topic is. A filled
`circle stands for “basic knowledge,” a half-
`filled circle indicates “standard knowledge,”
`and an empty circle stands for “in-depth
`knowledge.” Of course,
`this classification
`only reflects our subjective views.
`This second edition was carefully revised and
`a significant number of new plates were
`added to cover new developments.
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
`CUREVAC EX2027
`Page 6
`
`

`

`VIII
`
`Contents
`
`Introduction . . . . . . . . . . . . . . . . . . . .
`
`1
`
`Basics
`Chemistry
`Periodic table. . . . . . . . . . . . . . . . . . . .
`Bonds . . . . . . . . . . . . . . . . . . . . . . . . .
`Molecular structure . . . . . . . . . . . . . . .
`Isomerism . . . . . . . . . . . . . . . . . . . . . .
`Biomolecules I . . . . . . . . . . . . . . . . . . .
`Biomolecules II . . . . . . . . . . . . . . . . . .
`Chemical reactions. . . . . . . . . . . . . . . .
`Physical Chemistry
`Energetics . . . . . . . . . . . . . . . . . . . . . .
`Equilibriums . . . . . . . . . . . . . . . . . . . .
`Enthalpy and entropy. . . . . . . . . . . . . .
`Reaction kinetics . . . . . . . . . . . . . . . . .
`Catalysis . . . . . . . . . . . . . . . . . . . . . . .
`Water as a solvent . . . . . . . . . . . . . . . .
`Hydrophobic interactions. . . . . . . . . . .
`Acids and bases . . . . . . . . . . . . . . . . . .
`Redox processes. . . . . . . . . . . . . . . . . .
`
`Biomolecules
`Carbohydrates
`Overview. . . . . . . . . . . . . . . . . . . . . . .
`Chemistry of sugars . . . . . . . . . . . . . . .
`Monosaccharides and disaccharides . . .
`Polysaccharides: overview . . . . . . . . . .
`Plant polysaccharides. . . . . . . . . . . . . .
`Glycosaminoglycans and glycoproteins .
`Lipids
`Overview. . . . . . . . . . . . . . . . . . . . . . .
`Fatty acids and fats . . . . . . . . . . . . . . .
`Phospholipids and glycolipids . . . . . . .
`Isoprenoids . . . . . . . . . . . . . . . . . . . . .
`Steroid structure . . . . . . . . . . . . . . . . .
`Steroids: overview . . . . . . . . . . . . . . . .
`Amino Acids
`Chemistry and properties. . . . . . . . . . .
`Proteinogenic amino acids . . . . . . . . . .
`Non-proteinogenic amino acids . . . . . .
`Peptides and Proteins
`Overview. . . . . . . . . . . . . . . . . . . . . . .
`Peptide bonds . . . . . . . . . . . . . . . . . . .
`Secondary structures . . . . . . . . . . . . . .
`
`2
`4
`6
`8
`10
`12
`14
`
`16
`18
`20
`22
`24
`26
`28
`30
`32
`
`34
`36
`38
`40
`42
`44
`
`46
`48
`50
`52
`54
`56
`
`58
`60
`62
`
`64
`66
`68
`
`Structural proteins . . . . . . . . . . . . . . . .
`Globular proteins . . . . . . . . . . . . . . . . .
`Protein folding . . . . . . . . . . . . . . . . . . .
`Molecular models: insulin. . . . . . . . . . .
`Isolation and analysis of proteins . . . . .
`Nucleotides and Nucleic Acids
`Bases and nucleotides. . . . . . . . . . . . . .
`RNA . . . . . . . . . . . . . . . . . . . . . . . . . . .
`DNA . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Molecular models: DNA and RNA . . . . .
`
`70
`72
`74
`76
`78
`
`80
`82
`84
`86
`
`Metabolism
`Enzymes
`88
`Basics. . . . . . . . . . . . . . . . . . . . . . . . . .
`90
`Enzyme catalysis . . . . . . . . . . . . . . . . .
`92
`Enzyme kinetics I . . . . . . . . . . . . . . . . .
`94
`Enzyme kinetics II . . . . . . . . . . . . . . . .
`96
`Inhibitors . . . . . . . . . . . . . . . . . . . . . . .
`98
`Lactate dehydrogenase: structure . . . . .
`Lactate dehydrogenase: mechanism . . . 100
`Enzymatic analysis . . . . . . . . . . . . . . . . 102
`Coenzymes 1 . . . . . . . . . . . . . . . . . . . . 104
`Coenzymes 2 . . . . . . . . . . . . . . . . . . . . 106
`Coenzymes 3 . . . . . . . . . . . . . . . . . . . . 108
`Activated metabolites . . . . . . . . . . . . . . 110
`Metabolic Regulation
`Intermediary metabolism . . . . . . . . . . . 112
`Regulatory mechanisms . . . . . . . . . . . . 114
`Allosteric regulation . . . . . . . . . . . . . . . 116
`Transcription control . . . . . . . . . . . . . . 118
`Hormonal control . . . . . . . . . . . . . . . . . 120
`Energy Metabolism
`ATP . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
`Energetic coupling . . . . . . . . . . . . . . . . 124
`Energy conservation at membranes. . . . 126
`Photosynthesis: light reactions . . . . . . . 128
`Photosynthesis: dark reactions . . . . . . . 130
`Molecular models: membrane proteins . 132
`Oxoacid dehydrogenases. . . . . . . . . . . . 134
`Tricarboxylic acid cycle: reactions . . . . . 136
`Tricarboxylic acid cycle: functions . . . . . 138
`Respiratory chain . . . . . . . . . . . . . . . . . 140
`ATP synthesis . . . . . . . . . . . . . . . . . . . . 142
`Regulation . . . . . . . . . . . . . . . . . . . . . . 144
`Respiration and fermentation . . . . . . . . 146
`Fermentations . . . . . . . . . . . . . . . . . . . 148
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
`CUREVAC EX2027
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`

`

`Carbohydrate Metabolism
`Glycolysis. . . . . . . . . . . . . . . . . . . . . . . 150
`Pentose phosphate pathway . . . . . . . . . 152
`Gluconeogenesis. . . . . . . . . . . . . . . . . . 154
`Glycogen metabolism . . . . . . . . . . . . . . 156
`Regulation . . . . . . . . . . . . . . . . . . . . . . 158
`Diabetes mellitus . . . . . . . . . . . . . . . . . 160
`Lipid Metabolism
`Overview . . . . . . . . . . . . . . . . . . . . . . . 162
`Fatty acid degradation . . . . . . . . . . . . . 164
`Minor pathways of fatty acid
`degradation . . . . . . . . . . . . . . . . . . . . . 166
`Fatty acid synthesis . . . . . . . . . . . . . . . 168
`Biosynthesis of complex lipids . . . . . . . 170
`Biosynthesis of cholesterol . . . . . . . . . . 172
`Protein Metabolism
`Protein metabolism: overview . . . . . . . 174
`Proteolysis . . . . . . . . . . . . . . . . . . . . . . 176
`Transamination and deamination . . . . . 178
`Amino acid degradation . . . . . . . . . . . . 180
`Urea cycle . . . . . . . . . . . . . . . . . . . . . . 182
`Amino acid biosynthesis . . . . . . . . . . . . 184
`Nucleotide Metabolism
`Nucleotide degradation. . . . . . . . . . . . . 186
`Purine and pyrimidine biosynthesis . . . 188
`Nucleotide biosynthesis . . . . . . . . . . . . 190
`Porphyrin Metabolism
`Heme biosynthesis . . . . . . . . . . . . . . . . 192
`Heme degradation . . . . . . . . . . . . . . . . 194
`
`Organelles
`Basics
`Structure of cells . . . . . . . . . . . . . . . . . 196
`Cell fractionation . . . . . . . . . . . . . . . . . 198
`Centrifugation . . . . . . . . . . . . . . . . . . . 200
`Cell components and cytoplasm . . . . . . 202
`Cytoskeleton
`Components. . . . . . . . . . . . . . . . . . . . . 204
`Structure and functions . . . . . . . . . . . . 206
`Nucleus . . . . . . . . . . . . . . . . . . . . . . . . 208
`Mitochondria
`Structure and functions . . . . . . . . . . . . 210
`Transport systems . . . . . . . . . . . . . . . . 212
`Biological Membranes
`Structure and components . . . . . . . . . . 214
`Functions and composition . . . . . . . . . . 216
`Transport processes . . . . . . . . . . . . . . . 218
`Transport proteins . . . . . . . . . . . . . . . . 220
`Ion channels. . . . . . . . . . . . . . . . . . . . . 222
`Membrane receptors . . . . . . . . . . . . . . 224
`
`Contents
`
`IX
`
`Endoplasmic Reticulum and Golgi Apparatus
`ER: structure and function. . . . . . . . . . 226
`Protein sorting . . . . . . . . . . . . . . . . . . 228
`Protein synthesis and maturation . . . . 230
`Protein maturation . . . . . . . . . . . . . . . 232
`Lysosomes. . . . . . . . . . . . . . . . . . . . . . 234
`
`Molecular Genetics
`Overview . . . . . . . . . . . . . . . . . . . . . . 236
`Genome . . . . . . . . . . . . . . . . . . . . . . . 238
`Replication . . . . . . . . . . . . . . . . . . . . . 240
`Transcription. . . . . . . . . . . . . . . . . . . . 242
`Transcriptional control . . . . . . . . . . . . 244
`RNA maturation . . . . . . . . . . . . . . . . . 246
`Amino acid activation . . . . . . . . . . . . . 248
`Translation I: initiation . . . . . . . . . . . . 250
`Translation II: elongation and
`termination. . . . . . . . . . . . . . . . . . . . . 252
`Antibiotics . . . . . . . . . . . . . . . . . . . . . 254
`Mutation and repair . . . . . . . . . . . . . . 256
`Genetic engineering
`DNA cloning . . . . . . . . . . . . . . . . . . . . 258
`DNA sequencing . . . . . . . . . . . . . . . . . 260
`PCR and protein expression . . . . . . . . . 262
`Genetic engineering in medicine . . . . . 264
`
`Tissues and organs
`Digestion
`Overview . . . . . . . . . . . . . . . . . . . . . . 266
`Digestive secretions. . . . . . . . . . . . . . . 268
`Digestive processes . . . . . . . . . . . . . . . 270
`Resorption . . . . . . . . . . . . . . . . . . . . . 272
`Blood
`274
`Composition and functions . . . . . . . . .
`Plasma proteins. . . . . . . . . . . . . . . . . . 276
`Lipoproteins . . . . . . . . . . . . . . . . . . . . 278
`Hemoglobin . . . . . . . . . . . . . . . . . . . . 280
`Gas transport . . . . . . . . . . . . . . . . . . . 282
`Erythrocyte metabolism . . . . . . . . . . . 284
`Iron metabolism . . . . . . . . . . . . . . . . . 286
`Acid–base balance . . . . . . . . . . . . . . . . 288
`Blood clotting . . . . . . . . . . . . . . . . . . . 290
`Fibrinolysis, blood groups . . . . . . . . . . 292
`Immune system
`Immune response . . . . . . . . . . . . . . . . 294
`T-cell activation. . . . . . . . . . . . . . . . . . 296
`Complement system . . . . . . . . . . . . . . 298
`Antibodies . . . . . . . . . . . . . . . . . . . . . 300
`Antibody biosynthesis . . . . . . . . . . . . . 302
`Monoclonal antibodies, immunoassay . 304
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
`CUREVAC EX2027
`Page 8
`
`

`

`X
`
`Contents
`
`Liver
`Functions. . . . . . . . . . . . . . . . . . . . . . . 306
`Buffer function in organ metabolism . . 308
`Carbohydrate metabolism . . . . . . . . . . 310
`Lipid metabolism . . . . . . . . . . . . . . . . . 312
`Bile acids . . . . . . . . . . . . . . . . . . . . . . . 314
`Biotransformations . . . . . . . . . . . . . . . 316
`Cytochrome P450 systems . . . . . . . . . . 318
`Ethanol metabolism . . . . . . . . . . . . . . . 320
`Kidney
`Functions. . . . . . . . . . . . . . . . . . . . . . . 322
`Urine. . . . . . . . . . . . . . . . . . . . . . . . . . 324
`Functions in the acid–base balance. . . . 326
`Electrolyte and water recycling . . . . . . 328
`Renal hormones. . . . . . . . . . . . . . . . . . 330
`Muscle
`Muscle contraction . . . . . . . . . . . . . . . 332
`Control of muscle contraction. . . . . . . . 334
`Muscle metabolism I . . . . . . . . . . . . . . 336
`Muscle metabolism II. . . . . . . . . . . . . . 338
`Connective tissue
`Bone and teeth . . . . . . . . . . . . . . . . . . 340
`Calcium metabolism . . . . . . . . . . . . . . 342
`Collagens. . . . . . . . . . . . . . . . . . . . . . . 344
`Extracellular matrix . . . . . . . . . . . . . . . 346
`Brain and Sensory Organs
`Signal transmission in the CNS . . . . . . . 348
`Resting potential and action potential. . 350
`Neurotransmitters . . . . . . . . . . . . . . . . 352
`Receptors for neurotransmitters . . . . . . 354
`Metabolism . . . . . . . . . . . . . . . . . . . . . 356
`Sight . . . . . . . . . . . . . . . . . . . . . . . . . . 358
`
`Nutrition
`Nutrients
`Organic substances . . . . . . . . . . . . . . . 360
`Minerals and trace elements . . . . . . . . 362
`Vitamins
`Lipid-soluble vitamins . . . . . . . . . . . . . 364
`Water-soluble vitamins I . . . . . . . . . . . 366
`Water-soluble vitamins II . . . . . . . . . . . 368
`
`Hormones
`Hormonal system
`Basics . . . . . . . . . . . . . . . . . . . . . . . . . 370
`Plasma levels and hormone hierarchy. . 372
`Lipophilic hormones. . . . . . . . . . . . . . . 374
`Metabolism of steroid hormones . . . . . 376
`Mechanism of action . . . . . . . . . . . . . . 378
`
`Hydrophilic hormones . . . . . . . . . . . . . 380
`Metabolism of peptide hormones . . . . . 382
`Mechanisms of action . . . . . . . . . . . . . . 384
`Second messengers. . . . . . . . . . . . . . . . 386
`Signal cascades. . . . . . . . . . . . . . . . . . . 388
`Other signaling substances
`Eicosanoids . . . . . . . . . . . . . . . . . . . . . 390
`Cytokines . . . . . . . . . . . . . . . . . . . . . . . 392
`
`Growth and development
`Cell proliferation
`Cell cycle . . . . . . . . . . . . . . . . . . . . . . . 394
`Apoptosis . . . . . . . . . . . . . . . . . . . . . . . 396
`Oncogenes . . . . . . . . . . . . . . . . . . . . . . 398
`Tumors . . . . . . . . . . . . . . . . . . . . . . . . 400
`Cytostatic drugs . . . . . . . . . . . . . . . . . . 402
`Viruses . . . . . . . . . . . . . . . . . . . . . . . . . 404
`Metabolic charts. . . . . . . . . . . . . . . . . . 406
`Calvin cycle . . . . . . . . . . . . . . . . . . . . . 407
`Carbohydrate metabolism. . . . . . . . . . . 408
`Biosynthesis of fats and
`membrane liquids . . . . . . . . . . . . . . . . 409
`Synthesis of ketone bodies and steroids 410
`Degradation of fats and phospholipids . 411
`Biosynthesis of the essential
`amino acids . . . . . . . . . . . . . . . . . . . . . 412
`Biosynthesis of the non-essential
`amino acids . . . . . . . . . . . . . . . . . . . . . 413
`Amino acid degradation I . . . . . . . . . . . 414
`Amino acid degradation II. . . . . . . . . . . 415
`Ammonia metabolism. . . . . . . . . . . . . . 416
`Biosynthesis of purine nucleotides . . . . 417
`Biosynthesis of the pyrimidine nucleotides
`and C1 metabolism . . . . . . . . . . . . . . . . 418
`Nucleotide 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
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
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`
`

`

`34
`
`Biomolecules
`
`Overview
`
`The carbohydrates are a group of naturally
`occurring carbonyl compounds (aldehydes
`or ketones) that also contain several hydroxyl
`groups. The carbohydrates include single sug-
`ars (monosaccharides) and their polymers,
`the oligosaccharides and polysaccharides.
`
`A. Carbohydrates: overview ���
`
`Polymeric carbohydrates–above all starch, as
`well as some disaccharides–are important
`(but not essential) components of food (see
`p. 360). In the gut, they are broken down into
`monosaccharides and resorbed in this form
`(see p. 272). The form in which carbohydrates
`are distributed by the blood of vertebrates is
`glucose (“blood sugar”). This is taken up by the
`cells and either broken down to obtain energy
`(glycolysis) or converted into other metabo-
`lites (see pp.150–159). Several organs (partic-
`ularly the liver and muscles) store glycogen as
`a polymeric reserve carbohydrate (right; see
`p.156). The glycogen molecules are covalently
`bound to a protein, glycogenin. Polysaccha-
`rides are used by many organisms as building
`materials. For example, the cell walls of bac-
`teria contain murein as a stabilizing compo-
`nent (see p. 40), while in plants cellulose and
`other polysaccharides fulfill this role (see
`p. 42). Oligomeric or polymeric carbohydrates
`are often covalently bound to lipids or pro-
`teins. The glycolipids and glycoproteins
`formed in this way are found, for example,
`in cell membranes (center). Glycoproteins
`also occur in the blood in solute form (plasma
`proteins; see p. 276) and, as components of
`proteoglycans, form important constituents of
`the intercellular substance (see p. 346).
`
`B. Monosaccharides: structure ���
`
`The most important natural monosaccharide,
`D-glucose, is an aliphatic aldehyde with six C
`atoms, five of which carry a hydroxyl group
`(1). Since C atoms 2 to 5 represent chiral
`centers (see p. 8),
`there are 15 further
`isomeric aldohexoses in addition to D-glucose,
`although only a few of these are important in
`nature (see p. 38). Most natural monosaccha-
`rides have the same configuration at C-5 as
`D-glyceraldehyde–they belong to the D series.
`
`The open-chained form of glucose shown
`in (1) is found in neutral solution in less than
`0.1% of the molecules. The reason for this is an
`intramolecular reaction in which one of the
`OH groups of the sugar is added to the alde-
`hyde group of the same molecule (2). This
`gives rise to a cyclic hemiacetal (see p.10). In
`aldohexoses, the hydroxy group at C-5 reacts
`preferentially, and a six-membered pyran
`ring is formed. Sugars that contain this ring
`are called pyranoses. By contrast, if the OH
`group at C-4 reacts, a five-part furan ring is
`In solution, pyranose forms and
`formed.
`furanose forms are present in equilibrium
`with each other and with the open-chained
`form, while in glucose polymers only the
`pyranose form occurs.
`The Haworth projection (2) is usually used
`to depict sugars in the cyclic form, with the
`ring being shown in perspective as viewed
`from above. Depending on the configuration,
`the substituents of the chiral C atoms are then
`found above or below the ring. OH groups
`that lie on the right in the Fischer projection
`(1) appear under the ring level in the Haworth
`projection, while those on the left appear
`above it.
`As a result of hemiacetal formation, an ad-
`ditional chiral center arises at C-1, which can
`be present in both possible configurations
`(anomers) (see p. 8). To emphasize this, the
`corresponding bonds are shown here using
`wavy lines.
`The Haworth formula does not take ac-
`count of the fact that the pyran ring is not
`plain, but usually has a chair conformation. In
`B3, two frequent conformations of D-glucopy-
`ranose are shown as ball-and-stick models. In
`the 1C4 conformation (bottom), most of the
`OH groups appear vertical to the ring level, as
`in the Haworth projection (axial or a posi-
`tion). In the slightly more stable 4C1 confor-
`mation (top), the OH groups take the equato-
`rial or e position. At room temperature, each
`form can change into the other, as well as into
`other conformations.
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
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`

`

`A. Carbohydrates: overview
`
`Carbohydrates
`
`35
`
`H
`
`HO
`
`OH
`
`CH2OH
`O
`
`H
`OH H
`
`H
`OH
`
`H
`
`Transporter
`
`Other monosaccharides
`Glycogenin
`
`Glucose
`
`Mono-
`saccharide
`
`Glycoproteins
`
`Glycolysis
`
`Gluconeo-
`genesis
`
`Pyruvate
`
`Amino
`acids
`
`ATP
`CO2+H2O
`
`Glycolipids
`
`Glycogen
`
`Peptidoglycan
`(Murein)
`
`Periplasm
`
`Proteoglycans
`
`Bacterium
`
`B. Monosaccharides: structure
`
`4
`
`1
`
`4C1-conformation
`
`HO
`CH2
`H
`OH
`
`56
`
`H
`OH
`
`O
`C
`1
`
`H
`
`H
`
`4
`
`HO
`
`3
`H
`
`2
`OH
`
`Hemiacetal formation
`
`1
`
`4
`
`HO
`
`H
`
`O
`H
`
`H2
`
`HO
`H
`
`HC
`
`OH
`
`HO
`
`OH
`
`H
`
`HO
`
`CH2OH
`C
`H
`O
`OH H
`
`H
`
`Open-chained
`form (< 0.1%)
`
`O
`
`H
`
`1
`
`C C
`
`2 3 4 5 6
`
`H
`HO
`H
`H
`
`OH
`H
`C
`OH
`C
`C
`OH
`CH2OH
`Open-chained
`form of glucose
`
`Chiral
`center
`1. Fischer projection
`
`H OH
`H
`OH
`D-Gluco-
`D-Gluco-
`furanose (<1%)
`pyranose (99%)
`2. Ring forms (Haworth projection)
`
`1C4-conformation
`
`3. Conformations
`
`Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
`All rights reserved. Usage subject to terms and conditions of license.
`
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`

`

`36
`
`Biomolecules
`
`Chemistry of sugars
`
`A. Reactions of the monosaccharides ���
`
`The sugars (monosaccharides) occur in the
`metabolism in many forms (derivatives).
`Only a few important conversion reactions
`are discussed here, using D-glucose as an ex-
`ample.
`1. Mutarotation. In the cyclic form, as op-
`posed to the open-chain form, aldoses have a
`chiral center at C-1 (see p. 34). The corre-
`sponding isomeric forms are called anomers.
`In the β-anomer (center left), the OH group at
`C-1 (the anomeric OH group) and the CH2OH
`group lie on the same side of the ring. In the α-
`anomer (right), they are on different sides.
`The reaction that interconverts anomers into
`each other is known as mutarotation (B).
`2. Glycoside formation. When the anome-
`ric OH group of a sugar reacts with an alcohol,
`with elimination of water,
`it yields an
`O–glycoside (in the case shown, α –methylglu-
`coside). The glycosidic bond is not a normal
`ether bond, because the OH group at C-1 has a
`hemiacetal quality. Oligosaccharides and pol-
`ysaccharides also contain O-glycosidic bonds.
`Reaction of the anomeric OH group with an
`NH2 or NH group yields an N-glycoside (not
`shown). N-glycosidic bonds occur in nucleo-
`tides (see p. 80) and in glycoproteins (see
`p. 44), for example.
`3. Reduction and oxidation. Reduction of
`the anomeric center at C-1 of glucose (2) pro-
`duces the sugar alcohol sorbitol. Oxidation of
`the aldehyde group at C-1 gives the intramo-
`lecular ester (lactone) of gluconic acid (a gly-
`conic acid). Phosphorylated gluconolactone is
`an intermediate of the pent