PRINCIPLES OF
`BIOCHEMISTRY
`
`FOURTH EDITION
`
`Horton Moran
`
`Scrimgeour
`
`Perry Rawn
`
`1 of 169
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`Exhibit 1010
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`Librar)' of Congress Cataloging-io-Publication Data
`Principles of biuchemistry / H. Robert Horton .. , [er al.].-4th ed.
`p. cm.
`Includes bibliographical referenc~ and index,
`ISBN ~1 3-145306-8
`I. Bicid1en1i siry. I. Hollon, H. Robert.
`QP5 14.-.P745 2006
`612'.015-ck 22
`550•dc2:1
`
`.1005007745
`
`,ury Cml \o n
`Executive Ecli w r:
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`Abow 1he co1•,·1·: 1,rnpl "" Ill (ubiq11in,il:cytochrome c 0xidoreduccase). This
`membrane-bouncl rnmpkx plays a key ro le in membrane-associated electron
`lT.:tnsporl and the g.encn11 i, 111 < f the proton gradient that eventuall y gives rise
`to new ATP moleculeb, Complex m catalyze the Q-cycle reactions--0ne of
`the mo ·r important pathways in biochemistry. (See page 427 .)
`
`© 2006, 2002, 1996, 1993 by Pearson Education, Inc.
`Pearson Prenlice Hall
`Pearson Education , Inc.
`Upper Saddle River, New Jersey 07458
`
`Pearson Prentice HalJ'rM is a trademark of Pearson Education, Inc.
`
`All rights reserved. No part of this book may be
`reproduced, in any form or by any mean . . without
`pennission in writing from the publ i her.
`
`Printed in U1e United States of Ameri co
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`
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`
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`1
`
`chapter
`one
`
`Introduction
`to Biochemistr
`B iocbernistry is the srudy of the molecules and chemical reactions of life. It
`
`is the discipline that uses the principles and language of chemistry to ex(cid:173)
`plain biology at the molecular level. Biochemist have discovered that the
`~ame chemicaJ compounds and the same central metabolic processes are found in
`organisms as distantly related as bacteria, plants, and humans. It is now known that
`the basic principles of biochemistry are common ro all living organisms. Although
`scientists usually conceno-ate their research efforts on particular organisms, their
`re. ults can be applied to many other species.
`This book is called Principles of Biochemist,y because we wilJ focus on the
`most important and fundamenta l concepts ofbiochemi try: those that are common to
`most species, inclucling bacteria, plants, and mammals such as ourselves. Where ap(cid:173)
`propriate, we wilJ point out features t11at distinguish particular groups of organisms.
`Many students and researchers are primarily interested in the biochemistry of
`humans. The causes of disease and the importance of proper nutrition, for example,
`are fascinating topics in biochemistry. We • hare these interests, and that's why we
`include many references to human biochemistry in this textbook. However, we will
`also try to interest you in the biochemistry of other species. As it turns out, it is
`ofLen easier to understand basic principles of biochemistry by studying many dif(cid:173)
`ferent species in order to recognize common themes and patterns. A knowledge
`and appreciation of other species will do more than help you learn biochemistry. It
`wi ll also help you recogn ize the fundamental nature of life at the molecular level
`and the ways in which species are related through evolution from a common ances(cid:173)
`tor. Perhaps future editions of this book will include chapters on the biochemistry
`of life on other planets. Until then, we will have to be atisfied with learning about
`the diverse life on our own pl anet.
`We begin this introductory chapter with a few h.i.ghlights of the history of bio(cid:173)
`chemistry, followed by short descriptions of the chemical groups and molecule
`
`Top: Adenovirus. Viruses consist of a nucleic add molecule surrounded by a protein coaL
`
`1
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`2
`
`CHAPTER 1 ■ Introduction to Biochemistry
`
`4 Friedrich Wohler (1800-1882). By synthesiz(cid:173)
`ing urea, Wohler showed that compounds
`found in living organisms could be made in the
`laboratory from inorganic substances.
`
`4 Eduard Buchner (1860-191 7). Buchner dis(cid:173)
`covered cell-free fermentation.
`
`that you will encounter throughout this book. The second half of the chapter is an
`overview of cell structure in preparation for your study of biochemistry.
`
`1.1 Biochemistry Is a Modern Science
`
`Biochemistry has emerged as a dynamic science only within the past 100 years.
`However, the groundwork for the emergence of biochemistry a a modern science
`was prepared in earUer centuries. The period before 1900 saw rapid advances in the
`understanding of basic chemical principles such as reaction kinetics and the atom(cid:173)
`ic composition of molecules. Many chemicals produced in living orgarusms had
`been identified by the end of the 19th century. Since then, biochemistry has become
`an organized discipline, and biochemists have elucidated many of the chemical
`proces es of life. The growth of biochemistry and its influence on other discipline
`will continue in the 21st century.
`In 1828 Friedrich Wohler synthesized the organic compound urea by heating
`the inorganic compound ammonium cyanate.
`
`(1.1)
`
`Thi experiment showed for the first lime that compounds found exc lu sively in liv(cid:173)
`ing organism couJd be ynthesized from common inorganic substance . We now
`understand that the y □ thesis and degradation of biological substances obey the
`same chemical and physical laws as tho e that predominate outside of biology. No
`special or "vi tal istic" processes are required to explain life at the molecular level.
`Many scientists date the beginnings of biochemistry to Wohler's synthesis or urea,
`although it would be another 75 year before the first biochemistry departmenls
`were established at universities.
`Two major breakthrnughs in the hi tory of biochem.i try are especially no(cid:173)
`table-the discovery of the roles of enzymes as catalysts and the role of nucleic
`acid as information-carrying molecule . The very large size of proteins and nu (cid:173)
`cleic acids made their initial characterization difficult using the techniques avail(cid:173)
`able in the early part of the 20th century. With the development of modern
`technology we now know a great deal about how the struclures of proteins and nu(cid:173)
`cleic aci ds are related to their biological functions.
`The first breakthrough-identification of enzymes as the catalysts of biologi(cid:173)
`cal reactions-resulted in pait from the research of Eduard Buchner. In I 897 Buch(cid:173)
`ner showed that extract of yeast cells could catalyze the fermentalion of the sugar
`glucose to alcohol and carbon dioxide. Previously, scientists believed that only liv(cid:173)
`ing cells cou ld catalyze uch complex biological reactions.
`The nature of biological cataJysts was explored by Bucbner's contemporary,
`Emil Fischer. Fischer studied the catalytic effect of yeast enzymes on a simple reac(cid:173)
`tion . 1he hydrolysis (breakdown by water) of sucrose (table sugar). Fischer proposed
`that during catalysis an enzyme and its reactant, or substrate, combine to form an
`intermediate compound. He also proposed that only a molecule with a uitable
`, trucrw·e can erve as a substrate for a given enzyme. Fi cher described enzymes as
`rigid templates or locks, and substrates as matching keys. Reseai·chers soon realized
`that almosl all the reactions of life are catalyzed by enzymes, and the modified lock(cid:173)
`and-key theory of enzyme action remain a central tenet of modern biochemistry.
`As we will ee in Chapter 5, enzymatic catalysis produces very high yields
`with few. if any, by-products. In contra t, many catalyzed reaction~ in organic
`chemisu·y are considered acceptable with yields of 50% to 60%. Biochemical reac(cid:173)
`tions must be efficient since by-products can be toxic to cells and their formation
`would waste precious energy. Of course, the other key property of enzyme cataly-
`is is that biological reactions occur much faster than they would without a catalyst.
`
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`1. I • Biochemistry Is a Modern Science
`
`3
`
`.._ Emil Fischer (1852-1919). Fischer, w ho
`made many contributions to our understand(cid:173)
`ing of the structures and functions of biological
`molecules, proposed the lock-and-key th eory
`of enzyme action . He received the Nobel Prize
`in Chemistry in 1902 for his work on sugar and
`purine metabolism.
`
`The synl11esis of RNA (transcription) and
`protein (translation) are described in
`Chapters 21 and 22, respectively.
`
`ht: last half of the 20th century saw tremendous advances in the area of struc(cid:173)
`tural biology, especially the structure of proteins. The first protein structures were
`,til ed in the I 950s and 1960s by scientists at Cambridge University (United King(cid:173)
`JtJm) led by John C. Kendrew and Max Perutz. Since tJ1en, the three-dimen ional
`f mnre than 1000 different proteins have been detennined and our un(cid:173)
`, tructure:-
`di:r,tuncli ng of the complex bioi:hemistry of protein has increased enormously.
`The ·.: nip id ad vances were made possible by C-he availability of larger and fa ter
`~·omputcrs und new software that could carry out the many calculations that used to
`b done by hand using simple calculators. Much of modem biochemistry relies on
`c0mpu cers, and thi ha created a new subdiscipline called bioinformatics.
`The second major breakthrough in the history of biochemistry-identification
`111 nudeic acids as information molet:ule -came a half-century after Buchner's
`:inu Fisc her's experiments. In 1944 Oswald Avery, Co)jn MacLeod, and Maclyn
`~ikC:i rty extracted deoxyribonucleic acid (DNA) from a toxic strain of the bacter(cid:173)
`ium Strepwcoccus pneumoniae and mixed the DNA with a nontoxic
`train of the
`,ame organism. The nontoxic strain was thereby permanently transformed into a
`to · ic strain. This experiment provided the ftrst conclusive evidence that DNA is the
`genetic material. rn 1953 James D. Wat on and Francis H. C. Crick deduced the
`1hrce-dimen ional structure of DNA. The tructure of DNA immediately sugge ted
`to Wat on and Crick a method whereby DNA could reproduce itself, or replicate,
`c1 11d lhus transmit biological information to succeeding generations. Sub equem re(cid:173)
`~enn:h showed that information encoded in D1 A i transcribed to ribonucleic acid
`(RNA) and then tran lated into protein.
`
`D A -
`
`RNA -
`
`Protein
`
`(1.2)
`
`The study of genetics at the level of nucleic acid molecules is part of the di ci(cid:173)
`plii1e of molecular biology, and molecular biology is part of the di cipline of bio(cid:173)
`chemistry. ln order to understand how nucleic acids store and transmit genetic
`in fo rmation, you must understand the structure of nucleic acids and their role in en(cid:173)
`l·c1ding the enzyme proteins that catalyze the synthesis and degradation of biomol(cid:173)
`ccuks, including the nucleic acids themselves. You will find that much of your
`study of biochemistry is devoted to considering how enzymes and nucleic acids are
`centrnl to the chemistry of life.
`As Crick predicted in 1958, ilie normal flow of information from nucleic acid to
`protein is not reversible. He refeITed to this unidirectional information flow as the
`Ce ntral Dogma of molecular biology. The term "Central Dogma" is often misunder(cid:173)
`tood. Strictly speaking, it does not refer to the overall flow of information shown
`above. Instead, it refers to the fact that once information in nucleic acid
`is trans(cid:173)
`fen-ed to protein it cannot flow backwards from protein to nucleic acids.
`
`1 .2 The Chemical Elements of Life
`
`Six. nonmetallic elements-ox.ygen, carbon, hydrogen, nitrogen, phosphorus. and
`sulfur-account for more than 97% of the weight of most organi ms. All the e ele(cid:173)
`ments can form stable covalent bonds. The relative amounts of iliese six elements
`vary among organisms. Water is a major component of cells and accounts for the
`high percentage (by weight) of ox.ygen. Carbon is much more abundant in living
`organisms than in the rest of the universe. On ilie other hand. some elements, such
`a
`ilicon, aluminum, and iron are very common in the Earth' s crust but are present
`only in trace amoums in cells. Altogether, a total of 29 different elements are com(cid:173)
`monly found in living organisms (Figure 1.1, on page 4). These include ftve ions
`that are essential in all species: calcillm (Ca~, potassium (KE!)), sodium (NaE!)) ,
`magne ium (Mg~, and chloride (Cl8) Note that the additional 29 elements ac(cid:173)
`count for only 3% of the weight of living organisms.
`
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`

`4
`
`CHAPTER I • In troduction to Biochemistry
`
`68 ~ 69
`61
`71
`70
`67
`66
`65
`64
`63
`62
`60
`59
`53,,,
`Lu I
`Eu
`Dy
`Er
`Tm Yb
`Ho
`Tb
`Gd
`Sm
`Pm
`Nd
`Pr
`Ce
`167 .3
`I 68.9 I 173.0 ~
`~l--•1 .... 0 -~l-t---1 __ 40.c.·~9-t-1~44:-=.2-+-.._1~4'"'5'-+--I 5=0'-'-.4--+--J~52 __ .0---+ .... l-'-5 ... 7 . __ 3-+-'1"'5=8.~9-i-~l 6 __ 2=.5_, 164.9
`100
`IQ]
`102
`103
`90**
`91
`92
`93
`94
`95
`96
`97
`98
`) 99
`Th I Pa
`Fm Md No
`Lr
`U
`Np
`Pu
`Am
`Cm Bk
`Cf
`Es
`~23~2~.0~~2~3~1 ~ 2=3~s~.0~~23~ 7~~'2~44~~=24~3~~--47~-=2 __ 47~1~='2=s=1 ~ (252) Lill.IL (258)
`(259J ___(lffi_ I
`
`Figure 1.1 •
`Periodic table of the elements. The important elements found in living cells are shown in color. The brown elements (CHNOPS) are the six
`abundant elements. The five essential ions are purple. The trace elements are shown in dark blue (more common) and ligh t blue (less
`common).
`
`Most of the olid materi al of cells consist of carbon-containing compounds.
`The s1udy of such compounds falls inlo the domain of organic chemi~try. There is
`considerable overlap between the disciplines of organic chemi. lry aml biod1e111-
`istry. and a course in organic chemistry i helpful in underslanding biochemistry.
`Organic chernists are more inlerested in reactions thai take place in the labormory.
`whereas biochemists would like to undersland how reactions occur in living cells.
`The types of organic compounds commonly encountered in biochemistry are
`shown in Figure 1.2a.
`Biochemical reactions involve specific chemical bonds or purls f 111olecL1les
`called functional groups. The most important of these site of reuctivity are shown
`in Figure 1.2b. Figure 1.2c illu trates some types of Jinkages present in derivative
`of the compounds shown in Figure 1.2a. Note that all of the. e linkage consist of
`several different atom and individual bonds be1ween at m . . We will encounter
`these compounds functional groups, and ]jnknges thrnughout this book. Ester and
`ether linkages are common in Fatty acids and lipids. Amide linkages are round in
`proteins. Phosphate ester and phosphoanhydride linkages m.:cllr i11 nut:lcotides.
`An impnrtant theme of biochemisu·y i that the chemical reactions 1h:.11 occur
`inside cell are th~ sa me kinds of reactions that take place in a chemi, try labora(cid:173)
`lory. The most imporl unt difference is that almost all reactions that occ:ur in Ii ing
`cells are cutal yzed by enzy mes and lhus proceed at very high ra tes. One of the main
`goals of thi s 1e:~ tb ok is 10 C..\pl ,1 in how enzymes speed up reaction~ withnut violat(cid:173)
`ing the fund amental reac1ion mechnni.~m of organic chemi stry. The ca1:1l yti c effi(cid:173)
`ciency of enzymes c::rn be obse rved even when the en;,ymes and reactanl s are
`isolated u1 a lest tube. Researchers often find it useful to di~tinguish between bio(cid:173)
`chemical reactions that 1c1ke plai.:e in an organism (in vii'o) :mtl those that occur
`under laboratory conditions (in 1·i1J-o).
`
`6 of 169
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`

`1.2 ■ The Chemical Elements of Life
`
`5
`
`◄ f igure 1.2
`General formulas of (a) organic compounds,
`(b) functional groups, and (c) linkages com(cid:173)
`mon fn biochemistry. R represents an alkyl
`group (CH3 -( CH2)n-)·
`
`1 Under mosr biological conditions. carboxylic
`0
`acids exist as carboxy late anions:
`
`II R-c - oe
`
`2 Under most biological conditions, amines ex.i t as
`ammonium ions: R,
`R 1
`Ell
`(:D I
`@
`R-NH 3 , R-NH 1 ,and R-NH-R1
`
`(a) Organic compounds
`
`R-OH
`Alcol10I
`
`R- H
`Thiul
`(Stilfhytl ryl)
`
`0
`II
`R-C-H
`Aldehyde
`
`R-NH2
`Primary
`
`0
`II
`R-C -R 1
`Ketone
`
`R,
`I
`R- H
`Secondary
`
`Amines 2
`
`0
`II
`R-C-OH
`Carboxylic acid 1
`
`R,
`I
`R-N-R 2
`Tertiary
`
`{b) Fw1crio11al groups
`
`-OH
`Hydroxyl
`
`- SH
`Sulfhydryl
`(Thiol)
`
`0
`II
`-C-R
`Acyl
`
`0
`II
`-c-
`Carbonyl
`
`-NH2 or
`Amino
`
`(±)
`H3
`
`0
`II
`-o-P-08
`I
`oe
`Phospha1e
`
`0
`II
`-c-08
`Carboxylate
`
`0
`II
`-p-oe
`I
`oe
`Phosphoryl
`
`(c) Linkages in biochemical compounds
`
`0
`II
`I
`-c-o-c-
`1
`
`Ester
`
`I
`I
`-c-o-c-
`1
`I
`
`Ether
`
`0
`II
`-N-C-
`1
`Amide
`
`0
`II
`I
`-C- O-P-08
`I
`Phospbate ester
`
`60
`
`0
`0
`II
`II
`-O-P-0-P-0-
`1
`I
`oe
`oe
`Phosphoanhydride
`
`1.3 Many Important Macromolecules Are Potymers
`
`Chemical structures are the vocabulary of biochemistry. We present some of these
`structures to prepare you for the examples you will encounter in the next few chap(cid:173)
`ters. Much of biochemistry deals with very large molecules that we refer to as
`macromolecules. Biological macromolecules are usually a form of polymer created
`by joining many smaller organic molecules, or monomers, via condensation (re(cid:173)
`moval of tbe elements of water). Each monomer incorporated into a macromolecu(cid:173)
`lar chain is termed a re. idue. ln some cases, such as certain carbohydrntes, a single
`re idue is repealed many times; in other cases such , s pr Leins and nucleic acids, a
`
`7 of 169
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`

`6
`
`CHAPTER 1 •
`
`Introduction to Biochemistry
`
`(a)
`
`I Hl
`I
`II , -C-H
`I
`R
`
`(bl
`
`0
`II
`e
`H N-CH-C - N-CH-coo0
`'
`I
`I
`I
`R
`H
`R
`
`Figure 1.3 .4
`Structure of an amino acid and a dipeptide.
`(a) All amino acids contain an amino group
`(blue) and a carboxylate group (red). Different
`amfno acids contain different side chains (des•
`ignated -R). (b) A dipeptide is produced
`when the amino group of one amino acid re(cid:173)
`acts With the carboxylate group of another to
`form a peptide bond (red).
`
`variety of resjdues are connected in a particular order. Each residue of a given poly(cid:173)
`mer is added by repeating the same enzyme-catalyzed reaction. Thu , all of the res(cid:173)
`idues in a macromolecule are aligned in the same direction, and the ends of the
`macromolecule are chemicaUy distinct.
`Macromolecules have properties that are very different from those of their
`constituent monomers. For example, starch is not soluble in water and does not
`caste sweet, although it is a polymer of the sugar glucose. Observations such as this
`have Jed to the general principle of the hierarchical organization of li fe. Each new
`level of organization results in properties that cannot be predicted solely from those
`of the previous level. The levels of complexity, in increasing order, are atoms, mol(cid:173)
`ecules. macromolecules. organelles, cell s, tissues, organs. and whole organjsms.
`(Note that many species Jack one or more of these levels of complexity. Single(cid:173)
`celled organisms, for example, do not have tissues and organs.) The following sec(cid:173)
`tions briefly describe the principal types of macromolecules and how their
`sequences of residues or three-dimensional shapes grant them unique properties.
`In discussing molecules and macromolecules, we will often refer to the molec(cid:173)
`ular weight of a compound. A more precise term for molecular weight is relative
`molecular mass (abbreviated Mr), It is the mass of a molecule relative to I/ 12 the
`mass of an atom of the carbon isotope t 2C. (The atomic weight of this isotope bas
`been defined as exactly 12 atomic mass units. ote that the atomic weight of car(cid:173)
`bon shown in the Periodic Table represents the average of several differem iso(cid:173)
`topes, including 13C and 14C.) Because Mr is a relative quantity, it is dimensionless
`and has no units associated with its value. The relative molecular mass of a typical
`protein, for example, is 38 000 (Mr= 38 000). The absolu te molecular mass of a
`compound has the same magnitude as the molecular weight except that it is ex(cid:173)
`pressed in units called daltons (1 dalton = 1 atomic ma s unit). The molecular
`mass is also called the molar mass because it represents the mass (measured in
`grams) of l mole, or 6.023 X I 023 molecules. The molecular mass of a typical pro(cid:173)
`tein is 38 000 dalton . which means that 1 mole weighs 38 kilograms. The main
`source of confu ion is that the term "molecular weight" has become common jar(cid:173)
`gon in biochemi cry although it refers to relative molecular mass and not to weight.
`It is a common error to give a molecular weight in daltons when it hould be di(cid:173)
`mensionless. 1n mos1 cases this isn't a very important mistake, but you should
`know the correct terminology.
`
`A. Proteins
`
`Twenty common amino acids are incorporated into proteins in all cells. Each amino
`acid contains an amino group and a carboxylate group. as well as a side chain
`(R group) that is unique to each amino acid (Figure 1.3a). 111e amino group of one
`amino acid and the carboxylate group of another are condensed during protein syn(cid:173)
`thesis to form an amide linkage as shown in Figure 1.3b. Tbe bond between the car(cid:173)
`bon atom of one amino acid residue and the nitrogen atom of tbe next residue is
`called a peptide bond. Tbe end-to-end joinjng of many amino acids forms a linear
`polypeptide that may contain hundred of amino acid residues . A functional pro(cid:173)
`tein can be a ingle polypeptide, or it can consist of several different polypeptide
`chains that are tightly bound to form a more complex structure.
`Many proteins function as enzymes. Other are . tructural components of cell
`and organisms. The three-dimensional shape of a protein is determined largely by
`the sequence of it amino acid residues. This sequence information is encoded in
`the gene for the protein. The function of a pn 1ein depenJs on its thn::e-dimensional
`~trudure, or conformation. The srructw·es of many proteins have be 11 determined,
`und several principles governing the relationship between strui;ture and function
`huve be ome clear. For example, many enzymes contain a cleft, or groove, that
`binds the substrates of a reaction . This cavity contains the active site of the en(cid:173)
`zyme-the region where the chemical renc1ion takes place. Figure 1.4a shows
`the structure of the e11zyme ly ozyme, which catalyze the hydrolysis of specific
`
`8 of 169
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`

`(a)
`
`(b)
`
`1.3 • Many lmportan l Macromolecules Are Polymers
`
`7
`
`Figure 1.4 •
`Chicken (Gallus gal/us) egg white lysozyme. (a) Free lysozyme. Note the characteristic cleft
`tha t includes the active site of the enzyme. (b) Lysozyme with bound substrate. [PDB 1 LZC].
`
`carbohydrate polymers. ote tbe prominent cleft in the molecule. This cleft is the
`site of substrate binding and enzymatic activity. Figure 1.4b shows the structure of
`!he enzyme with the substrate bound in the cleft. We wiU discuss the relationship
`between protein structure and function further in Chapters 4 and 6.
`There are many ways of representing the three-dimensional structures of
`biopolymers such as proteins. The protein molecule in Figure 1.4 is shown as a car(cid:173)
`LOon where the conformation of the polypeptide chain is represented as a combi(cid:173)
`nation of wires, helical ribbons, and broad arrows. Other kinds of representations in
`the follow ing chapters include images that show the position of every atom. Com(cid:173)
`puter programs that create these images are freely available on the Internet, and the
`structural data for proteins can be retrieved from a number of database sites. With a
`li trle practice any student can view these molecules on a computer monitor.
`
`B. Polysaccharides
`
`Carbohydrates, or saccharides, are composed primarily of carbon, oxygen, and hy(cid:173)
`drogen. This group of compounds includes simple sugars (monosaccharides) as
`well as their polymers (polysaccharides). All monosaccharides and all residues of
`polysaccharides contain several hydroxyl groups and are therefore polyalcohols.
`The most common monosaccharides contain either five or six carbon atoms.
`Sugar structures can be represented in several ways. For example, 1ibose (the
`most common five-carbon sugar) can be shown as a linear molecule containing
`four hydroxyl groups and one aldehyde group (Figure l.Sa on page 8). This linear
`representation is called a Fischer projection. In its usual biochemical form, howev(cid:173)
`er, the structure of ribose is a ring with a covalent bond between the carbon of the
`aldehyde group (C-1) and the oxygen of the C-4 hydroxy l group as shown in Fig(cid:173)
`ure l.Sb. The ring form is most commonly shown as a Haworth projection (Fig(cid:173)
`ure l.Sc). This representation is a more accurate way of depicting the actual
`structure of ribose. The Haworth projection is rotated 90° with respect to the
`Fischer projection and portrays the carbohydrate ring as a plane with one edge pro(cid:173)
`jecting out of the page (represented by the thick lines). However, the ring is not ac(cid:173)
`tually planar. le can adopt numerous conformations in which certain ring atoms are
`out-of-plane. In Figure l.Sd. for example, the C-2 atom of ribose lies above the
`plane formed by the rest of the ring atoms.
`Some conformations are more stable than others, so the majority of ribose
`molecules can be represented by one or two of the many possible conformations.
`Nevertheless, it's important to note that most biochemical molecules exist as a
`
`9 of 169
`
`Fresenius Kabi
`Exhibit 1010
`
`

`

`8
`
`CHAPTER 1 • Introduction to Biochemistry
`
`(a)
`
`H
`0
`~ /
`,c
`I
`H -C- OH
`' 1
`H-C-OH
`' I
`H-C-OH
`• I
`5CH 20H
`
`(b)
`
`(c)
`
`(d)
`
`s
`HOC~H
`2 O
`OH
`• H
`H
`H
`
`H
`
`z
`J
`OH OH
`
`I
`
`HOC~ 2 °/ OH
`
`H
`
`l
`
`I
`OH H
`
`,
`H
`
`;
`HO
`
`Fischer projection
`(open-chain form)
`
`Pischer pr Jection
`(ring form)
`
`Haworth projection
`
`Envelope conformation
`
`Conformations nf monosaccharides are de(cid:173)
`SCI lbed 111 more delail in Section 8. 3.
`
`Figure 1.5 &
`Representations of the structure of ribose. (a) In the Fischer projection, ribose is drawn as a
`linear molecule. (b) In its usual biochemical form, the ribose molecule is in a ring, shown
`here as a Fischer projection. (c) In a Haworth projection, the ring is depicted as lying per(cid:173)
`pendicular to the page (as indicated by the thick lines, which represent the bonds closest to
`the viewer). (d) The ring of ribose is not actually planar but can adopt 20 possible conforma(cid:173)
`tions in which certain ring atoms are out-of-plane. In the conformation shown, C-2 lies
`above the plane formed by the rest of the ring atoms.
`
`collection of structures with different conformations. By definition, the change
`from one conformation to another does not require the breaking of any covalent
`bonds. In contrast, the two basic forms of carbohydrate structures, linear and rin g
`forms, do require the breaking and forming of covalent bonds.
`Glucose is the mo t abundant six-carbon sugar Figure 1.6a). It is the
`monomeric unit of cellulose, a structural poly accharide, and of glycogen and
`starch, wbich are storage polysaccharides . lo these polysacchaiides each glucose
`residue is joined covalently to the next by a covalent bond between C-1 of one glu(cid:173)
`cose molecule and one of the hydroxyl groups of another. This bond is called a gly(cid:173)
`cosidic bond. In cellulose, C-1 of each gl ucose residue is joined to the C-4
`hydroxyl group of the next re idue (Figure 1.6b). The hydroxyl groups on adjacent
`chains of cellulose interact noncovalently, creating strong, insoluble fibers. Cellu(cid:173)
`lose i:; probably the most abundant biopolymer on Earth because it is a major
`component of flowering plant stems, including tree trunks. We wi ll discuss carbo(cid:173)
`hydrates further in Chapter 8.
`
`Figure 1.6 ►
`Glucose and cellulose. (a) Haworth projection
`of glucose. (b} Cellulose, a linear polymer of
`glucose residues. Ear. h residue is joined to the
`next by a glycosidic bond (red) .
`
`6
`CH ,OH
`,· 0 OA
`
`4
`
`~
`HO
`
`I
`
`H
`
`OH
`
`H
`
`J
`H
`
`e
`OH
`
`(a)
`
`(b)
`
`0..,,,..,.
`
`10 of 169
`
`Fresenius Kabi
`Exhibit 1010
`
`

`

`ucleic Acids
`
`Nucleic acids are large macromolecules composed of monomers called nu(cid:173)
`clGotides. Tbe termpolynucleotide is a more accurate description of a single mole(cid:173)
`cu le of nucleic acid, just a polypeptide is a more accurate te,m than prozein for
`~i ngle molecules composed of amino acid re idues. The term nucleic acid refers to
`Lhe fact that the e polynncleotides were first derected a acidic molecule in the nu(cid:173)
`clt:us of eukaryotic cells . We now know that nucleic acids are not confined to the
`t:ukaryotic nucleus but are abundant in the cytoplasm and in prokaryotes that don't
`have a nucleus.
`Nucleotides con ist of a five-carbon sugar, a heterocyc!ic nitrogenou base,
`and at least one phosphate group. In ribonucleotides, the sugar is ribose: in de(cid:173)
`oxyribonucleotides, it is the derivative deoxyribose (Figure l. 7). The nitrogenou
`ba~es of nucleotides belong to two families known as purines and pyrimidines. The
`n1ajor purines are adenine (A) and guanine (G); the major pyrimidines are cyto ine
`(C), thymine (T), and uracil (U). In a nucleotide, the base is joined to C- l of
`the ugar, and the phosphate group is attached to one of the other sugar carbons
`(usually C-5).
`The structure of the nucleotide adenosine triphosphate (ATP) is hown in Fig(cid:173)
`ure J .8. ATP consists of an adenine moiety linked to ribose by a glycosidic bond .
`There are three phosphoryl groups (designated a, {3, and -y) e terified to the C-5
`hydroxyl group of the ribose. The linkage between ribose and the a-phosphoryl
`group is a phosphoester linkage because it includes a carbon and a phosphorus
`m m. whereas the {3 and 'Y phosphoryl groups in ATP are connected by phospho(cid:173)
`anhydride linkages that don't involve carbon aloms. All phosphoanhydrides pos(cid:173)
`,e~s considerable chemical potential energy, and ATP is no exception. It is the
`ccnlral can-ier of energy in living cells. The potential energy associated with the
`bonds between the phospboryl groups of ATP can be used directly in biochemical
`reactions or coupled to a reaction in a less obviou way. In condensation reactions,
`for example, transfer of one of the phospboryl groups of ATP results in the forma(cid:173)
`tion of an activated intermediate which then participates in the synthetic reaction.
`We will encounter many condensation reactions that involve ATP.
`In polynucleotidcs, the phosphate group of one nucleotide is covalently linked
`tn the C- ~ oxygen atom of the sugar of another nucleotide, creating a ~econd phos(cid:173)
`phoesler linkage. The entire linkage between the carbons of adjacent nu leo1ides is
`culled a phosphodiester linkage because it contains two phosphoester linkages (Fig(cid:173)
`ure 1.9, on page I 0). ucleic acids contain many nucleotide residues and are char(cid:173)
`acterized by ,1 backbone consisting of alternating sugars and phosphates. Tn DNA.
`lhe bases of 1wu different polynucleotide "tram.ls interact lo fo rm a helic:.il structure.
`There are several ways of depicting nucleic acid structures dep