throbber
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
`Page 7
`
`

`

`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.
`
`CUREVAC EX2027
`Page 9
`
`

`

`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.
`
`CUREVAC EX2027
`Page 10
`
`

`

`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.
`
`CUREVAC EX2027
`Page 11
`
`

`

`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

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket