MOLECULAR BIOLOGY OF
`
`THIRD EDITION·
`
`Bruce Alberts • Dennis Bray
`Julian Lewis •Martin Raff• Keith Roberts
`James D. Watson
`
`Garland Publishing, Inc.
`NewYork&London
`
`Page i
`
`Illumina Ex. 1037
`IPR Petition - USP 10,435,742
`
`

`

`Text Editor: Miranda Robertson
`Managing Editor: Ruth Adams
`Illustrator: Nigel Orme
`Molecular Model Drawings: Kate Hesketh-Moore
`Director of Electronic Publishing: John M-Roblin
`Computer Specialist: Chuck Bartelt
`Disk Preparation: Carol Winter
`Copy Editor: Shirley M. Cobert
`Production Editor: Douglas Goertzen
`Production Coordinator: Perry Bessas
`Indexer: Maija Hinkle
`
`Bruce Alberts received his Ph.D. from Harvard University and is
`currently President of the National Academy of Sciences and Professor
`of Biochemistry and Biophysics at the University of California, San
`Francisco. Dennis Bray received his Ph.D. from the Massachusetts
`Institute of Technology and is currently a Medical Research Council
`Fellow in the Department of Zoology, University of Cambridge.
`Julian Lewis received his D.Phil. from the University of Oxford and is
`currently a Senior Scientist in the Imperial Cancer Research Fund
`Developmental Biology Unit, University of Oxford. Martin Raff received
`his M.D. from McGill University and is currently a Professor in the MRC
`Laboratory for Molecular Cell Biology and the Biology Department,
`University College London. Keith Roberts received his Ph.D. from the
`University of Cambridge and is currently Head of the Department of Cell
`Biology, the John Innes Institute, Norwich. James D. Watson received his
`Ph.D. from Indiana University and is currently Director of the Cold Spring
`Harbor Laboratory. He is the author of Molecular Biology of the Gene and,
`with Francis Crick and Maurice Wilkins, won the Nobel Prize in Medicine
`and Physiology in 1962.
`
`© 1983, 1989, 1994 by Bruce Alberts, Dennis Bray, Julian Lewis,
`Martin Raff, Keith Roberts, and James D. Watson.
`
`All rights reserved. No part of this book covered by the copyright hereon
`may be reproduced or used in any form or by any means-graphic,
`electronic, or mechanical, including photocopying, recording, taping, or
`information storage and retrieval systems-without permission of the
`publisher.
`
`Library of Congress Cataloging-in-Publication Data
`Molecular biology of the cell I Bruce Alberts ... [et al.] .. -3rd ed.
`p. cm.
`Includes bibliographical references and index.
`ISBN 0-8153-1619-4 (hard cover).-ISBN 0-8153-1620-8 (pbk.)
`1. Cytology. 2. Molecular biology. I. Alberts, Bruce.
`[DNLM: 1. Cells. 2. Molecular Biology. QH 581.2 M718 1994]
`QH581.2.M64 1994
`574.87-dc20
`DNLM/DLC
`for Library of Congress
`
`93-45907
`CIP
`
`Published by Garland Publishing, Inc.
`717 Fifth Avenue, New York, NY 10022
`
`Printed in the United States of America
`15 14 13 12 10 9 8 7.
`
`Front cover: The photograph shows a rat nerve cell
`in culture. It is labeled (yellow) with a fluorescent
`antibody that stains its cell body and dendritic
`processes. Nerve terminals (green) froi;n other
`neurons (not visible), which have made synapses on
`the cell, are labeled with a different antibody.
`(Courtesy of Olaf Mundigl and Pietro de Camilli.)
`Dedication page: Gavin Borden, late president
`of Garland Publishing, weathered in during his
`mid-1980s climb near Mount McKinley with
`MBoC author Bruce Alberts and famous mountaineer
`guide Mugs Stump (1940-1992).
`Back cover: The authors, in alphabetical order,
`crossing Abbey Road in London on their way to lunch.
`Much of this third edition was written in a house just
`around the corner. (Photograph by Richard Olivier.)
`
`Page ii
`
`

`

`amino
`
`group \ H
`
`carboxyl
`
`group I
`
`I
`H2N-C-COOH -
`I
`pH 7
`CH 3
`nonionized
`form
`
`ionized
`form
`
`Figure 2-6 The amino acid alanine.
`In the cell, where the pH is close to 7,
`the free amino acid exists in its
`ionized form; but when it is
`incorporated into a polypeptide
`chain, the charges on the amino and
`carboxyl groups disappear. A ball(cid:173)
`and-stick model and a space-filling
`model are shown to the right of the
`structural formulas. For alanine, the
`side chain is a -CH3 group.
`
`the hydrophobic tail regions pack together very closely facing the air and the
`hydrophilic head groups are in contact with the water (Panel 2-4, pp. 54--55). Two
`such films can combine tail to tail in water to make a phospholipid sandwich, or
`lipid bilayer, an extremely important assembly that is the structural basis of all
`cell membranes (discussed .in Chapter 10).
`
`Amino Acids Are the Subunits of Proteins 5
`The common amino acids are chemically varied, but they all contain a carboxylic
`acid group and an amino group, both linked to a single carbon atom (called the
`a-carbon; Figure 2-6). They serve as subunits in the synthesis of proteins, which
`are long linear polymers of amino acids joined head to tail by a peptide bond
`between the carboxylic acid group of one amino acid and the amino group of the
`next (Figure 2-7). Although there are many different possible amino acids, only
`20 are common in proteins, each with a different side chain attached to the
`a-carbon atom (Panel 2-5, pp. 56-57). The same 20 amino acids occur over and
`over again in all proteins, including those made by bacteria, plants, and animals.
`Although the choice of these particular 20 amino acids probably occurred by
`chance in the course of evolution, the chemical versatility they provide is vitally
`important. For example, 5 of the 20 amino acids have side chains that can cany
`a charge (Figure 2-8), whereas the others are uncharged but reactive in specific
`ways (Panel 2-5, pp. 56-57). As we shall see, the properties of the amino acid side
`chains, in aggregate, determine the properties of the proteins they constitute and
`underlie all of the diverse and sophisticated functions of proteins.
`
`Nucleotides Are the Subunits of DNA and RNA 6
`In nucleotides one of several different nitrogen-containing ring compounds (of(cid:173)
`ten referred to as bases because they can combine with H+ in acidic solutions) is
`linked to a five-carbon sugar (either ribose or deoxyribose) that carries a phos(cid:173)
`phate group. There is a strong family resemblance between the different nitro(cid:173)
`gen-containing rings found in nucleotides. Cytosine (C), thymine (T), and uracil
`(U) are called pyrimidine compounds because they are all simple derivatives of
`a six-membered pyrimidine ring; guanine (G) and adenine (A) are purine com(cid:173)
`pounds, with a second five-membered ring fused to the six-membered ring. Each
`mlcleotide is named by reference to the unique base that it ,contains (Panel 2-
`6, pp.58-59).
`Nucleotides can act as carriers of chemical energy. The triphosphate ester of
`adenine, ATP (Figure 2-9), above all others, participates in the transfer of energy
`in hundreds of individual cellular reactions. Its terminal phosphate is added using
`energy from the oxidation of foodstuffs, and this phosphate can be split off readily
`by hydrolysis to release energy that drives energetically unfavorable biosynthetic
`reactions elsewhere in the cell. As we discuss later, other nucleotide derivatives
`serve as carriers for the transfer of particular chemical groups, such as hydrogen
`atoms or sugar residues, from one molecule to another. And a cyclic phosphate-
`
`46 Chapter 2 : Small Molecules, Energy, and Biosynthesis
`
`Phe
`
`Ser
`
`Lys
`
`~____J
`carboxyl end
`of chain
`
`Figure 2-7 A small part of a protein
`molecule, showing four amino acids.
`Each amino acid is linked to the next
`by a covalent peptide bond, one of
`which is shaded yellow. A protein is
`therefore also sometimes referred to
`as a polypeptide. The amino acid side
`chains are shown in red, and the
`atoms of one amino acid (glutamic
`acid) are outlined by the gray box.
`
`amino encl
`of chain
`r - - ; - - i
`l
`N-H
`H-~-CHrO\
`
`·
`
`-
`
`O=C
`I
`N-H
`I
`H-~-CH 2 -0H
`O=C
`I
`··.
`· .. ··N-H.
`
`8-;~ '....cH 2-CH 2_:< .· _
`
`. O
`
`. . . ··o
`
`:O~C
`. I·'
`H
`N-H
`>
`/
`I
`H-C -CH 2-CH 2-CH 2-0-1 2 -N-H·
`I
`~
`H
`O=T
`
`

`

`13
`
`11
`
`9
`
`7
`
`5
`
`3
`
`pH
`
`Figure 2--8 The charge on amino acid
`side chains depends on the pH.
`Carboxylic acids readily lose H+ in
`aqueous solution to form a negatively
`charged ion, which is denoted by the
`suffix "-ate," as in aspartate or
`·glutamate. A comparable situation
`exists for amines, which in aqueous
`solution take up H+ to form a
`positively charged ion (which does
`not have a special name). These
`reactions are rapidly reversible, and
`the amounts of the two forms,
`charged and uncharged, depend on
`the pH of the solution. At a high pH,
`carboxylic acids tend to be charged
`and amines uncharged. At a low pH,
`the opposite is true-the carboxylic
`acids are uncharged and amines are
`charged. The pH at which exactly half
`of the carboxylic acid or amine
`residues are charged is known as the
`pK of that amino acid side chain.
`In the cell the pH is close to 7,
`and almost all carboxylic acids and'\
`amines are in their fully charged form ..
`
`aspartic
`acid
`pK-4.7
`
`glutamic
`acid
`pK-4.7
`
`histidine
`
`pK-6.5
`
`lysine
`
`pK-10.2
`
`arginine
`
`pl<-12
`
`containing adenine derivative, cyclic AMP, serves as a universal signaling mol(cid:173)
`ecule within cells.
`The special significance of nucleotides is in the storage of biological infor(cid:173)
`mation. Nucleotides serve as building blocks for the construction of nucleic
`acids, long polymers in which nucleotide subunits are covalently linked by the
`formation of a phosphate ester between the 3'-hydroxyl group on the sugar resi(cid:173)
`due of one nucleotide and the 5' -phosphate group on the next nucleotide (Fig-
`
`Figure 2-9 Chemical structure of
`adenosine triphosphate (ATP). A
`space-filling model (A), a ball-and(cid:173)
`stick model (B), and the structural
`formula (C) are shown. Note the
`negative charges on each of the three
`phosphates.
`
`(Al
`
`(8)
`
`(C)
`
`1 triphosphate J
`
`ribose
`
`adenine
`aclenosine
`
`The Chemical Components of a Cell
`
`47
`
`

`

`HYDROGEN BONDS
`
`Because they are polarized, two
`adjacent H20 molecules can form
`a linkage known as a hydrogen
`bond. Hydrogen bonds have
`only about 1/20 the strength
`of a covalent bond.
`
`Hydrogen bonds are strongest when
`the three atoms lie in a straight line.
`
`llllllllll
`
`hydrogen bond
`
`bond lengths
`
`hydro.gen bond
`0.28 nm
`
`O 1111111111111111111 H-0-
`
`L___J
`0.104 nm
`covalent bond'
`
`H
`
`H
`
`"" /
`
`WATER
`Two atoms, connected by a covalent bond, may exert different attractions for
`the electrons of the bond. In such cases the bond is dipolar, with one end
`slightly negatively charged (8-) and the other slightly positively charged (o+).
`A bond in which both atoms are the same, or in which they attract electrons
`equally, is called non polar.
`
`WATER STRUCTURE
`
`Molecules of water join together transiently
`in a hydrogen-bonded lattice. Even at 37°C,
`15% of the water molecules are joined to
`four others in a short-lived assembly known
`as a "flickering ciuster."
`
`electronegative
`region
`
`Although a water molecule has an overall neutral charge (having the same
`number of electrons and protons}, the electrons are asymmetrically distributed,
`which makes the molecule polar. The oxygen nucleus draws electrons away
`from the hydrogen nuclei, leaving these nuclei with a small net positive charge.
`The excess of electron density on the oxygen atom creates weakly negative
`regions at the other two corners of an imaginary tetrahedron.
`
`The cohesive nature of water is
`responsible for many of its unusual
`properties, such as high surface tension,
`specific heat, and heat of vaporization.
`
`HYDROPHILIC AND HYDROPHOBIC MOLECULES
`Because of the polar nature of water molecules, they
`will cluster around ions and other polar molecules.
`
`Nonpolar molecules interrupt the H-bonded
`structure of water without forming favorable
`interactions with water molecules. They are
`therefore hydrophobic and quite insoluble
`in water.
`
`H
`I
`H-0
`
`H
`\
`0-H
`
`I
`0
`\
`
`H
`
`H
`
`0
`H/ ......__H
`
`Na+
`
`Cl~
`
`H-0
`\
`H
`
`0-H
`I
`H
`
`I
`0
`\
`
`H
`
`H
`
`H
`\
`0
`I
`H
`
`0-H
`I
`H
`H
`=
`I
`01111111H-O
`I
`-C
`\
`
`H
`I
`O-H11111110
`\
`H
`
`H
`\
`0-H
`
`'
`Molecules that can thereby be accommodated in water's
`hydrogen-bonded structures are hydrophilic and
`relatively water-soluble.
`
`

`

`HYDROPHOBIC MOLECULES AND CLATHRATE WATER STRUCTURES
`
`Molecules that are nonpolar and cannot form
`hydrogen bonds-such as hydrocarbons(cid:173)
`have only limited solubility in water and are
`called hydrophobic. In water, ordered cages
`of water molecules are formed around
`hydrocarbons. These icelike cages,
`called "clathrate structures," are relatively
`more ordered than water and cause
`an entropy decrease of the mixture. Part
`of a clathrate cage (red) surrounding a
`hydrocarbon (black) is shown. In the intact
`cage, each oxygen atom (red circles) would
`be tetrahedrally coordinated to four others.
`
`An acid is a molecule that releases an H+
`.:Jon (proton) in solution. For example,
`
`0
`II
`CH3-\
`
`OH
`
`acid
`
`0
`!
`~
`CH-C
`~ 3
`\
`o-
`
`+
`
`base
`
`proton
`
`'A base is a molecule that accepts an H+
`;ion (proton) in solution. For example,
`
`base
`
`proton
`
`acid
`
`Water itself has a slight tendency to ionize and
`can act both as a weak acid and as a weak base.
`When it acts as an acid, it releases a proton to
`form a hydroxyl ion. When it acts as a base,
`it accepts a· proton to form a hydronium ion.
`Most protons in aqueous solutions exist as
`hydronium ions.
`
`H
`I
`O-HlllllllllO
`I
`\
`
`II Jf
`
`H
`
`+
`
`08
`I
`H
`hydroxyl ion
`
`H
`I
`H-0
`0\
`H
`hydronium ion
`
`H+
`cone.
`moles/liter
`
`The. acidity of a
`solution is defined
`by the concentration
`of W ions it possesses.
`For convenience we
`use the pH scale where
`
`JI ~~~:
`
`10-9
`10-10
`10-11
`
`10-12
`
`10-13
`
`10-14
`
`~
`
`pH
`
`2
`3
`4
`
`5
`
`6
`7
`8
`8
`10
`11
`12
`13
`·14
`
`OSMOSIS
`If two aqueous solutions are separated by a membrane
`that allows only water molecules to pass, water will move
`into the solution containing the greatest concentration of
`solute molecules by a process known as osmosis.
`. ' .
`...
`... .. ' . . '
`' ..
`This movement of water from a hypotonic to a hypertonic
`solution can cause an increase in hydrostatic pressure in
`the hypertonic compartment. Two solutions that have
`identical solute concentrations and are therefore osmotically
`balanced are said to be isotonic.
`
`9
`
`0
`
`o o
`
`• f) • •
`
`

`

`CARBON Sl<ELETONS
`The unique role of carbon in the cell comes from its
`ability to form strong covalent bonds with other
`carbon atoms. Thus carbon atoms can join to form
`-
`chains.
`
`\/ \/ \/ \/
`/c~c/c~c/c~c/c~c/
`/\ /\ /\' /\
`
`or branched trees
`
`or rings
`
`also written as VV\/\
`
`also written as >--< . I
`
`also written as (X)
`
`COVALENT BONDS
`A covalent bond forms when two atoms come very close
`together and share one or more of their electrons. In a single
`bond one electron from each of the two atoms is shared; in
`a double bond a total of four electrons are shared.
`Each atom forms a fixed number of covalent bonds in a
`defined spatial arrangement. For example, carbon forms four
`single bonds arranged tetrahedrally, whereas nitrogen forms
`three single bonds and oxygen forms two single bonds arranged
`as shown below.
`
`Double bonds exist and have a different spatial arrangement.
`
`Atoms joined by two
`or more covalent bonds
`cannot rotate freely
`about the bond axis.
`This restriction is a
`major influence on the
`'three-dimensional shape
`of many macromolecules.
`
`HYDROCARBONS
`
`Carbon and hydrogen together
`make stable compounds called
`hydrocarbons. These are
`nonpolar, do not form hydrogen
`bonds, and are generally
`insoluble in water.
`
`H
`I
`H-C-H
`I
`H
`
`methane
`
`H
`I
`H-C-
`j
`H
`
`methyl group
`
`RESONANCE AND AROMATICITY
`The carbon chain can include double
`bonds. If these are on alternate carbon
`atoms, the bonding electrons move
`within the molecule, stabilizing the
`structure by a phenomenon called
`resonance.
`
`I
`C
`
`\=I \c=I
`c
`I
`\
`I
`\
`C=C
`C=C
`I t \
`\
`I
`the truth is somewhere between
`these two structures
`I l \
`I
`\
`c
`c-c
`c-c
`\_! \_!
`I
`\
`I
`\
`I
`
`When resonance occurs
`throughout a ring compound,
`an aromatic ring is generated.
`
`H
`
`H
`
`H
`
`H
`
`H
`
`H
`
`H
`
`H
`
`often written as 0
`
`part of a
`fatty acid chain
`
`._-_-·o?-'
`
`~~ -~~~. -]
`
`

`

`c-O COMPOUNDS
`. Many biological compounds contain a carbon
`bonded to an oxygen. For example,
`
`H
`I
`-C-OH
`I
`H
`
`0
`
`-c //
`\
`
`The -OH is called a
`hydroxyl group.
`
`The C=O is called a
`carbonyl group.
`
`0
`
`-c //
`\ H
`
`The -COOH is called a
`carboxyl group. In water
`this loses an Wion to
`become -coo-.
`
`Esters are formed by combining an
`acid and an alcohol.
`
`0
`I
`//o
`//
`~
`I + H 0
`-· c-c
`I ~
`~\ +
`'D-c- 2
`I
`OH HO-C-
`l
`I
`alcohol
`
`ester
`
`C-N COMPOUNDS
`Amines and amides are two important examples of
`compounds containing a carbon linked to a nitrogen.
`Amines in water combine with an H+ ion to become
`positively charged.
`
`They are therefore basic.
`Amides are formed by combining an acid and an
`amine. They are more stable than esters. Unlike
`amines, they are uncharged in water. An example
`is the peptide bond.
`0
`-ell +
`\OH
`
`I
`H N-C-
`I
`2
`
`0
`//
`- - \ I +H20
`N-C-
`~ I
`Nitrogen also occurs in several ring compounds, including
`important constituents of nucleic acids: purines Emd pyrimidines.
`
`Phosphate esters can form between a phosphate
`and a free hydroxyl group.
`
`0
`. .
`II
`HO-P-0-
`. I
`o-
`
`~
`I
`-C-OH + HO-P""--'-0-
`6-
`
`1
`
`I
`-C-O-P-0-
`
`1
`
`~
`6-
`
`also
`written as
`
`I -c-o-®
`I
`
`of a phosphate and a carboxyl group, or two or more phosphate groups, gives an acid anhydride.
`
`0
`//
`-c
`\OH
`
`0
`0
`II ~
`'//
`-c
`+ HO-P-ff ~
`.. \
`I o-
`II o-r-o-
`I o-
`
`0
`
`+
`
`H20
`
`also written as
`0
`-c //
`'o-®
`
`0
`0
`0
`0
`II
`II
`II
`II
`.-. -0- Pc-OH + HO-P-0- ~
`-O-P-O-P-0-
`I
`I ~
`I
`I
`o-
`o-
`07
`o-
`
`+ H20
`
`also written as
`
`-o--®-®
`
`

`

`HEXOSES n = 6
`Two common hexoses are
`fructose
`glucose
`H
`0
`H
`I
`f' c
`"
`H-C-OH
`I
`I
`C=O
`H-C-OH
`I
`I
`HO-C-H
`HO-C-H
`I
`I
`H-C-OH
`H-C-OH
`I
`I
`H-C-OH
`H-C-OH
`I
`I
`H-C-OH
`H-C-OH
`I
`I
`H
`H
`
`MONOSACCHARIDES
`Monosaccharides are
`aldehydes or ketones
`
`(-<:) ( >=O)
`
`that also have two or more hydro>syl groups.
`Their general formula is (CH 20)n. The
`simplest are trioses (n = 3) such as
`0
`H
`f' c
`"
`I
`H-C-OH
`I
`CH 20H
`glyceraldehyde (an aldose)
`CH 20H
`I
`C=O
`I
`CH20H
`dihydroxyacetone (a ketose)
`
`PENTOSES n = 5
`
`A common pentose is
`0
`H
`f' c
`"
`I
`H-C-OH
`I
`H-C-OH
`I
`H-C-OH
`I
`H-C-OH
`I
`H
`
`ribose
`
`o-ribose (open,-chain form)
`
`D-glucose (open-chain form)
`6
`CH 20H
`st--oH
`~/8
`4C
`l""?H ~/ ~O
`HO c--c2
`I
`13
`OH
`H
`
`'l/H
`C
`
`\
`
`CH 20H·
`I
`""'I
`H C-·. -.-0 H
`1/8
`i·C
`··
`.
`C
`I'\.. OH H/· I
`er-er
`I OH
`HO '\I
`
`H
`
`OH
`
`I
`
`tH20H
`c-. -. -o
`""?H
`~/~
`c
`c· ·
`I'\.. OH H/i
`. I H
`HO '\.I
`c - c
`I
`I
`OH
`H
`
`B-o-glucose
`
`a-o-glucose
`
`STEREO\SOMERS
`
`RING FORMATION
`The aldehyde or ketone group of a
`sugar can react with a hydroxyl group
`H
`H
`H
`H·
`I
`I
`I
`/
`-c +
`-C - 0 -C -
`HO-C- -
`I
`I
`i
`~
`0
`OH
`For the larger sugars (n>4) this
`happens within the same molecule
`to form a 5- or 6-membered ring.
`
`NUMBERING
`The carbon atoms of a sugar are
`numbered from the end closest
`to the aldehyde or ketone.
`
`CH 20H
`
`I
`1/0.~~H
`. c
`c'
`~/I
`H T-T H
`1"-~
`
`OH OH
`
`CH 20H
`
`\
`j/0~7
`c
`.
`c
`~/I
`1"-111
`H c - c OH
`I
`I
`OH OH
`
`. B-o-ribose
`
`a-o-ribose
`
`STEREO ISOMERS
`
`ISOMERS
`Monosaccharides have many isomers that differ only in the
`orientation of their hydroxyl groups-e.g., glucose, mannose,
`and galactose are isomers of each other.
`
`o AND L FORMS
`Two isomers that are mirror images of each other have the
`same chemistry and therefore are given the same name and
`distinguished by the prefix Dor L.
`
`glucose
`
`man nose
`
`QCHzOH
`
`H
`
`FHO
`I
`
`OH
`
`D-glucose
`
`- \
`
`\
`
`OH
`
`}_ ___________ ~
`
`galactose
`
`OH
`~f1f~1~J1Kli!\t~lri~{t4i~l~;~~)J!i&~1~~t~~ftl!lfu4tl~fli\:_i~liJ1
`.· Pahd 2'-3 An outli~e of~b1ne of the types of sugars comil1ol1ly f<?und ill cells.
`
`L-glucose
`
`mirror plane
`
`0
`
`

`

`SUGAR DERIVATIVES
`The hydroxyl groups of a simple monosaccharide can be replaced by
`other groups. For example,
`
`, ,a-AND ~-LINKS
`• The hydroxyl group on the carbon that carries the
`aldehyde or ketone can rapidly change fr.om one
`position to another. These two positions are called
`·a- and~-.
`
`0 ~OH"" P-hydroxyl
`Zzt~~~n?\ ~ /a-hydroxyl
`
`OH
`
`The carbon that carries the aldehyde or
`".ti1e ketone can react with any hydroxyl group
`:;;on a second sugar molecule to form a
`glycosidic bond. Three common disaccharides
`~kre maltose (glucose o:1,4 glucose), lactose
`r(galactose ~1,4 glucose), and sucrose
`~·(glucose o:1,2 fructose). Sucrose is shown here.
`
`~-o-fructose
`
`NH
`I
`C=O
`I
`CH3
`
`'YoL!GOSACCHARIDES AND POLYSACCHARIDES
`.Large linear and branched molecules can be made from simple repeating units.
`;short chains are called oligosaccharides, while long chains are called
`':polysaccharides. Glycogen, for example, is a polysaccharide made entirely of
`'.glucose units joined together.
`
`In many cases a sugar
`sequence is nonrepetitive.
`Many different molecules are
`possible. Such complex
`oligosaccharides are usually
`linked to proteins or to lipids.
`
`NH
`I c=o
`
`I
`
`CH3 ~IT~
`H~
`
`a blood group
`oligosaccharide
`
`OH
`
`

`

`COMMON FATTY ACIDS
`
`These are carboxylic acids with
`long hydrocarbon tails.
`
`Hundreds of different kinds of fatty acids exist. Some have one or more double bonds
`and are said to be unsaturated.
`
`[
`
`This double bond
`is rigid and creates
`/a kink in the chain.
`The rest of the chain
`is free to rotate
`about the other C-C
`bonds.
`
`TRIGLYCERIDES
`
`Fatty acids are stored as an energy
`reserve (fat) through an ester linkage
`to glycerol to form triglycerides.
`
`stearic
`acid
`(C1al
`
`oleic
`acid
`(C1al
`
`CARBOXYL GROUP
`
`If free, the carboxyl group of a
`fatty acid will be ionized.
`
`But more usually it is linked to
`other groups to form either esters
`
`0
`
`,/' c"
`I o-c-
`
`1
`
`or amides.
`
`PHOSPHOLIPIDS Phospholipids are the major constituents
`of cell membranes.
`
`polar
`head group
`
`a phospholipid
`
`0
`I
`O=P-0-
`1
`0
`I
`Ci-12--CH--CH?
`-
`I
`I
`0
`0
`0
`0
`"c.?-
`"c.?-
`
`space-filling
`model of
`phosph ati dylch ol i ne,
`
`In phospholipids two of the -OH groups in _
`glycerol are linked to fatty acids while the thiJ
`-OH group is linked to phosphoric acid. Thi,
`phosphate is further linked to one of a variet)
`of small polar head groups (alcohols).
`
`

`

`. Fat~y acids have a hydrophilic head -~
`
`and a hydrophobic tail..~
`
`In water they can form a surface film
`or form small micelles.
`
`derivatives can form larger aggregates held together by hydrophobic forces:
`
`""''"'r'"'" form large spherical fat
`in the cell cytoplasm.
`
`Phospholipids and glycolipids form self-sealing lipid
`bilayers that are the basis for all cellular membranes.
`
`POLYISOPRENOIDS ·
`
`long chain polymers
`of isoprene
`
`o-
`
`1
`O=P-o-
`1
`0
`
`-I
`
`-I
`
`Lipids are defined as the water-insoluble
`molecules in cells that are soluble in organic
`solvents. Two other common types of lipids
`are steroids and polyisoprenoids. Both are
`made from isoprene units.
`
`0
`testosterone-male steroid hormone
`
`:.--:,
`
`.C~ikephospholipids, these compounds are composed of a hydrophobic
`•. r~gion, containing two long hydrocarbon tails, and a polar region,
`'_Wh;,h now 00"1,;n, ooe oc morn eogoc '"id"" eod no pho;~hote.?l-IH r~,1~~
`
`I CH
`C
`C
`""-c,..- 1 'c,..-
`2
`I H
`H
`
`sugar
`residue
`
`C-NH
`II
`0
`
`a simple
`glyco/ipid
`
`dolichol phosphate-used
`to carry activated sugars
`in the membrane-associated
`synthesis of glycoproteins
`and some polysaccharides
`
`hydrophobic region
`
`

`

`OPTICAL ISOMERS The a-carbon atom is asymmetric, which
`for two mirror image (or stereo-) isomers, D
`
`r··
`
`THE AMINO ACID
`The general formula of an amino acid js
`
`f•''" 7~a~:arbon atom
`amino -------1l;lj~;---cc ':-&Q2l;!i
`I
`--......___ carboxyl group
`group
`R
`-------------side-chain group
`
`R is commonly one of 20 different side chains.
`At pH 7 both the amino and carboxyl groups
`are ionized.
`
`H
`©
`G
`.1
`H3 N -CC- COO
`I .R
`
`PEPTIDE BONDS
`
`Amino acids are commonly joined together by an amide linkage,
`called a peptide bond.
`
`peptide bond: The four atoms in each gray box form a rigid
`planar unit. There is no freedom of rotation about the C-N
`
`H
`-lo
`H"
`1
`N-C-C
`I
`"
`R
`OH
`
`/
`H
`
`+
`
`H
`"
`/
`H
`
`0
`
`R
`I
`/
`N-C-C
`I
`"
`H
`OH
`
`H :o
`H
`R
`O
`"
`I
`II
`.
`I
`,1
`N-C ~C'--'N-C-C
`/
`I ··•
`· I
`I
`"
`H
`·~ H
`R
`OH
`
`Proteins are long polymers
`of amino acids linked by
`peptide bonds, and they
`are always written with the
`N-terminus toward the left.
`The sequence of this
`tripeptide is His Cys Val.
`
`amino or
`N-terminus
`
`""'
`
`·.
`
`I
`f_H 2
`c
`/.·'\.
`HN.·:······.CH
`l. I
`HC==NW
`
`These two single bonds, on either side of the rigid peptide
`exhibit a high degree of rotational freedom.
`
`SH
`I
`7 >~·
`TH2. Sec~ 7
`carboxyl or
`3-terminus
`+H N-c-. c N"---c-·-c:·. N-c-coo- ~
`
`3
`
`J ·v 11
`
`H.
`
`, 0
`
`·
`
`I
`/C'\
`CH3 CH 3
`
`FAMILIES OF
`AMINO ACIDS
`
`BASIC SIDE CHAJNS
`
`The common amino acids
`are grouped according to
`whether their side chains
`are
`.,
`acidic
`basic
`uncharged polar
`non polar
`
`These 20 amino acids
`are given both three-letter
`and one-letter abbreviations.
`
`Thus: alanine= Ala =A
`
`· lysine
`
`(Lys, or I<)
`
`atginirie
`
`(Arg, or R)
`
`histidine:
`
`(His, or H)
`
`-N-c-c~
`
`0
`II
`
`H
`I
`I
`I
`H CH 2
`I
`CH,
`I -
`CH,
`I -
`CH,
`I -
`NJ-13
`+
`
`This group is
`very basic
`because its
`positive chargei
`is stabilized by
`resonance.
`
`H
`0
`I
`II
`-N-C-C-
`1
`I
`H CH,
`I -
`CH,
`I ..
`CH 2
`I
`NH
`I
`,/' c"
`+H 2N
`NH2
`
`H
`0
`I
`II
`-N-C-C-
`1
`I
`H
`C!-12
`I
`c
`.'\.
`/
`HN
`CH
`l
`I
`HC=N~+
`/
`These nitrogens have a
`relatively weak affinity for an
`Wand are only partly positive
`at neutral pH.
`
`

`

`a~partic acid·.
`(Asp, or D)
`
`(Glu, or E)
`
`H
`0
`II
`I
`-N-C-C-
`1
`I
`H CH2
`I
`c
`,/' "'
`
`o-
`
`0
`
`H
`0
`I
`II
`-N-C-C-
`1
`I
`H Cf-12
`I
`Cf-12
`I
`,/' "'
`c
`
`o-
`
`0
`
`XJ~tno acids with uncharged polar side chains are relatively
`c;;fl\,Clrophilic and are usually on the outside of proteins, while
`'{he'side chains on nonpolar amino acids tend to cluster
`together on the inside. Amino acids with basic or acidic
`"side ch~ins are very polar, and they are nearly always found
`on th~ outside of protein molecules.
`.
`·'[he'one letter code in alphabetical order:
`
`,'.·.-.'.
`
`G = Gly
`H =His
`I =lie
`I<= Lys
`L =Leu
`
`M =Met
`N = Asn
`P =Pro
`0= Gin
`H = Arg
`
`S =Ser
`T= Thr
`V= Val
`W=Trp
`Y= Tyr
`
`'glutamihe
`
`(Gin, or Q)
`
`1-1
`0
`I
`II
`~N-C-C-
`1 I
`1-1 c~
`I
`/C
`
`H
`0
`I
`II
`-N-C-C-
`I
`I
`H c~
`!
`CH 2
`
`0 'N~---~~H,
`
`Although the amide N is not charged at
`neutral pH, it is polar.
`
`~hreohine
`(Thr, or T)
`
`H
`I
`
`0
`II
`
`· · tvr.(Jsjrie
`(Tyr, or Y)
`
`H
`I
`
`0
`II
`
`NONPOLAR SIDE CHAINS
`
`H
`0
`I
`II
`-N-C-C-
`1
`I
`1-1
`H
`
`(Ala, or A)
`
`0
`1-1
`II
`I
`-N-C-C-
`1
`I
`H Cf-13
`
`(Gly, or G)
`
`(Val, or V)
`
`H
`0
`I
`II
`-N-C-C-
`1
`I
`H CH
`Cf-13
`
`/ "'
`
`Cf-13
`
`(Leu, or L)
`
`(lie, or I)
`
`H
`0
`. I
`.II
`-N-C-C-
`1
`I
`H CH 2
`I
`CH
`CH3
`
`/ "'
`
`CH3
`
`0
`1-1
`II
`I
`-N-C-C-
`1
`I
`•
`H CH
`CH3
`
`/ "'
`
`CH2
`I
`CH3
`
`. pl"() line
`(Pro, or P)
`
`••····
`
`H
`0
`I
`II
`-N-C-C-
`""'
`/
`CH?
`~ /
`Cf-12
`(actually an
`imino acid)
`
`CH?
`-
`
`'· 'frlethipnin~·
`(Met, or M)
`
`H
`0
`I
`II
`-N-C-C-
`1
`I
`H Cf-12
`I
`CH I 2
`5-CH3
`
`0
`1-1
`I
`II
`-N-C-C-
`1
`I
`H CH2
`I
`SH
`
`'·ph~~ylal~rlfn~ :
`(Phe, or F)
`
`H
`0
`I
`II
`-N-C-C-
`1
`I
`
`H CH? 6-
`
`• ;;trYpfhf:lhan.·)
`(Trp, orW)
`
`H
`0
`I
`II
`-N-C-C-
`1
`I
`
`~)'''
`
`H
`
`cysteihe'
`
`(Cys, or C)
`
`Paired cysteines allow disulfide bonds to form in proteins.
`
`

`

`BASES
`
`The bases are nitrogen-containing ring
`compounds, either purines or pyrimidines.
`
`PHOSPHATES
`
`NUCLEOTIDES
`
`A nucleotide consists of a nitrogen-containing
`base, a 5-carbon sugar, and one or more
`phosphate groups.
`
`PHOSPHATE
`
`0
`II
`-o-P-0-CH
`I
`2
`o-
`
`BASIC SUGAR
`LINKAGE
`
`N-glycosidic
`
`bood~ ~·
`5 ~N
`
`The phosphates are normally joined to
`the C5 hydroxyl of the ribose or
`deoxyribose sugar. Mono-, di-, and
`triphosphates are common.
`
`0
`_0 _ ~ ~o-kHfa"
`I
`,t~f-
`o-
`
`as in
`AMP
`
`0
`0
`II
`II
`crr'c'
`-o- P-0- P-0--'CH''
`I
`I
`o-
`o-
`
`Y'f
`
`as in
`ADP
`
`0
`0
`0
`II
`II
`II
`_
`,ff,.'t" as in
`0- P-0- P-0- P-0-CH"
`I
`I
`I
`o-
`o-
`o-
`
`"y:sl ATP
`
`The phosphate makes a nucleotide
`negatively charged.
`
`SUGARS
`
`· · E~§~iq~-~J
`
`a 5-carbon sugar
`
`They are the
`subunits of
`the nucleic acids.
`
`OH
`OH
`r,§'.[Q~K~
`
`The base is linked to
`the same carbon (C1)
`used in sugar-sugar
`bonds.
`
`HO~M~H
`~~~
`
`~-o-RIBOSE
`used in ribonucleic acid
`
`two kinds are used
`
`OH
`
`OH
`
`Each numbered carbon on the sugar of a nucleotide is
`followed by a prime mark; therefore, one speaks of the
`"5-prime carbon," etc.
`
`~-o-2-DEOXYRIBOSE
`used in deoxyribonucleic aci
`
`H
`
`H
`
`OH
`
`H
`
`HOC~H2
`OH
`
`
`
`.
`
`

`

`NOMENCLATURE
`
`The names can be confusing, but the abbreviations are clear.
`
`adenosine
`
`guanosine
`
`cytosine
`
`cytidine
`
`uridine
`
`thymine
`
`thymidine
`
`ABBR,
`
`A
`
`G
`c
`
`u
`
`T
`
`Nucleotides are abbreviated by
`three capital letters. Some examples
`follow:
`
`AMP = adenosine monophosphate
`dAMP = deoxyadenosine monophosphate
`UDP = uridine di phosphate
`ATP = adenosine triphosphate
`
`BASE+ SUGAR= NUCLEOSIDE
`
`:<_NUCLEIC ACIDS
`~o> .:..·, __ \ ,;'
`'';Nucleotides are joined together by a
`,--phosphodiester linkage between 5' and
`-_-3' carbon atoms to form nucleic acids.
`;_The linear sequence of nucleotides in a
`,-,,,hucleic acid chain is commonly
`-abbreviated by a one-letter code,
`: Ac---G-C-T-T-A-C-A, with the 5'
`- cendof the chain at the left.
`
`0
`II
`-o-P-0-CH
`I
`2
`o-
`
`NUCLEOTIDES HAVE MANY OTHER FUNCTIONS
`
`They carry chemical energy in their easily hydrolyzed acid-anhydride bonds.
`
`?·?? <~
`
`o-ro-ro-ro-~ N
`
`example: ATP (or m)
`
`OH OH
`
`They combine with other groups to form enzymes.
`
`OH
`
`+
`
`0
`II
`-:-o-P-O-CH 2
`_-
`I
`o-
`
`OH
`
`l
`
`0
`5' encl of chain
`II
`5'
`~0-P-0-CH
`I
`2
`o-
`
`N~N
`l(_--;JG N>
`Hs-t -b-N-~ -t-b-N-~ -t-b ~b-o-~ -o-~ -O-~CN
`2 9-
`-:<_:: 0:_~--
`
`H H
`
`0 H H
`
`0 H CH H
`
`I
`I
`I
`H H H
`
`I
`I
`I
`H H H
`
`I
`I
`I
`HO CH3 H
`
`0
`
`I
`o-
`
`0
`
`I
`o-
`
`example: coenzyme A (CoA)
`
`They are used as specific signaling molecules in the cell.
`
`OH
`
`0
`I
`O= P-o-
`1 o-
`
`3' 0
`I
`-o-P=O
`I
`?
`
`5' CH 2
`
`example:
`cyclic AMP (cAMP)
`
`NH2
`
`<JCb
`
`O-~ N
`
`O=P
`
`I o-
`
`0
`
`OH
`
`

`

`5' end of chain
`
`__J
`
`3' end of chain
`Figure 2-rn A short length of
`deoxyribonucleic acid (DNA),
`showing four nucleotides. One of the
`. phosphodiester bonds that link
`adjacent nucleotides is shaded yellow,
`and one of the nucleotides is enclosed
`in a gray box. DNA and its close
`relative RNA are the nucleic acids of
`the cell.
`
`ure 2-10). There are two main types of nucleic acids, differing in the type of sugar
`that forms their polymeric backbone. Those based on the sugar ribose are known
`as ribonucleic acids, or RNA, and wntain the four bases A, U, G, and C. Those
`based on deoxyribose (in which the hydroxyl at the 2' position of ribose is replaced
`by a hydrogen) are known as deoxyribonucleic acids, or DNA, and qontain the
`four bases A, T, G, and C. The sequence of bases in a DNA or RNA polymer rep(cid:173)
`resents the genetic information of the living cell. The ability of the bases from
`different nucleic acid molecules to recognize each other by noncovalent inter(cid:173)
`actions (called base-pairing)-G with C, and A with either T (in DNA) or U (in
`RNA)-underlies all of heredity and evolution, as explained in Chapter 3.
`
`Summary
`Living organisms are autonomous, self-propqgating chemical systems. They are made
`from a distinctive and restricted set of small carbon-based molecules that are essen(cid:173)
`tially the same for eveiy living species. The main categories are sugars, fatty acids,
`amino acids, and nucleotides. Sugars are a primmy source of chemicaz'energy for
`cells and can be incorporated into polysaccharides for energy storage. Fatty acids are
`also important for energy storage, but their most significant function is in the fonna(cid:173)
`tion of cell membranes. Polymers consisting of amino acids co.nstitute the remark(cid:173)
`ably diverse and versatile macromolecules known as proteins. Nucleotides play a
`central part in energy transfer and also are the subunits from which the informa(cid:173)
`tional macromolecules, RNA and DNA, are made.
`
`Cells must obey the laws of physics and chemist1y. The rules of mechanics and
`of the conversion of one form of energy to another apply just as much to a cell
`as to a steam engine. There are, however, puzzli