SECOND EDITION
`
`Principles of Biochemistry
`
`with an Extended Discussion of Oxygen-Binding Proteins
`
`Albert L. Lehninger
`
`Late University Professor of Medical Sciences
`
`The Johns Hopkins University
`
`David L. Nelson
`
`Professor of Biochemistry
`
`University of Wisconsin—Madison
`
`Michael M. Cox
`
`Professor of Biochemistry
`
`University of Wisconsin—Madison
`
`SHIRE EX. 2021
`KVK v. SHIRE
`IPR2018—00293
`
`WORTH PUBLISHERS
`
`p.1
`
`
`
`p. 1
`
`SHIRE EX. 2021
`KVK v. SHIRE
`IPR2018-00293
`
`

`

`
`
`Principles of Biochemistry Second Edition
`
`Albert L. Lehninger, David L. Nelson, and Michael M. Cox
`Copyright © 1993, 1982 by Worth Publishers, Inc.-
`All rights reserved
`Printed in the United States of America
`
`Library of Congress Catalog Card N0. 94-60553
`ISBN: 0~87901~500-4
`
`ISBN: 0-87901—711—2 with supplement
`
`Printing:
`
`9
`
`8
`
`7
`
`Year: 00
`
`99 98
`
`Development Editor: Valerie Neal
`
`Design: Malcolm Grear Designers
`
`Art Director: George Touloumes
`
`Project Editor: Elizabeth Geller
`
`Production Supervisor: Sarah Segal
`
`Layout: Patricia Lawson
`Picture Editor: Stuart Kenter
`
`Illustration Design: Susan Tilberry
`
`Illustrators: Susan Tilberry, Alan Landau, and Joan Waites
`
`Computer Art: Laura Pardi Duprey and York Graphic Services
`
`Composition: York Graphic Services
`
`Printing and binding: R.R. Donnelley and Sons
`
`Cover: The active site of the proteolytic enzyme chymotrypsin, show-
`ing the substrate (blue and purple) and the amino acid residues (red
`and orange) critical to catalysis. Determination of the detailed
`reaction mechanism of this enzyme (described on pp. 223—226)
`helped to establish the general principles of enzyme action.
`
`Frontispiece: A View of tobacco ribulose-l,5-bisphosphate carboxylase
`(rubisco). This enzyme is central to photosynthetic carbon dioxide
`fixation; it is the most abundant enzyme in the biosphere. Different
`subunits are shown in blues and grays. Important active site residues
`are shown in red. Sulfates bound at the active site (an artifact of the
`crystallization procedure) are shown in yellow.
`
`Cover, frontispiece, and part opening images produced by Alisa Zapp (see
`Molecular Modeling credits, p. IC-4) and enhanced by Academy Arts.
`
`Illustration credits begin on p. IC-l and constitute a continuation of the
`copyright page.
`
`Worth Publishers
`
`33 Irving Place
`
`New York, NY 10003
`
`p. 2
`
`

`

`Organic Compounds Have Specific Shapes and Dimensions
`
`The four covalent single bonds that can be formed by a carbon atom are
`arranged tetrahedrally, with an angle of about 109.5° between any two
`bonds (Fig. 3—4) and an average length of 0.154 nm. There is free rota-
`tion around each carbon—carbon single bond unless very large or
`highly charged groups are attached to both carbon atoms, in which
`case rotation may be restricted. A carbon—carbon double bond is
`shorter (about 0.134 nm long) and rigid and allows little rotation about
`its axis. (Fig. 3—4). No other chemical element can form molecules of
`such widely different sizes and shapes or with such a variety of func-
`tional groups.
`
`Functional Groups Determine Chemical Properties
`
`Most biomolecules can be regarded as derivatives of hydrocarbons,
`compounds with a covalently linked carbon backbone to which only
`hydrogen atoms are bonded. The backbones of hydrocarbons are very
`stable. The hydrogen atoms may be replaced by a variety of functional
`groups to yield different families of organic compounds. Typical fami-
`lies of organic compounds are the alcohols, which have one or more
`hydroxyl groups; amines, which have amino groups; aldehydes and
`ketones, which have carbonyl groups; and carboxylic acids, which have
`carboxyl groups (Fig. 3—5).
`
`Hydroxyl
`
`_ __
`1_
`R CH2 0 H
`
`Ether
`
`1_
`
`_ 2
`_ _
`CH2 0 CH2 R
`
`R
`
`Carbonyl
`(aldehyde)
`
`Rl—CHz—(flj—H
`
`0
`
`A .
`mm
`
`Rl—CH ~N
`2
`
`/H
`
`\
`
`H
`
`Carbonyl
`(ketone)
`
`/Carboxyl
`
`Rl—CHz—C—CHZ—RZ
`ll
`0
`Rl—CHz—fi_0H
`
`O
`
`,.
`Wm"
`
`H
`R1_CH2_C_N/
`O
`
`H
`
`\
`
`H
`|
`R1_CH2_(‘-J1__H
`
`H
`
`I?
`III
`Rl—CHg—(IJ—C—H
`H H
`
`.
`
`.
`Guanidmo
`
`H
`
`H
`/
`|
`1
`R —CH2—N—(|IJ—N\
`N\
`HH
`
`|/’Imidazole
`
`Rl—CH2—/C=C\H
`HN
`N
`\c’
`IiI
`
`16:13
`Rl—CH 4/
`\CH
`2
`\\C—-C//
`
`H H
`
`Sulfhydryl
`\Aisulfide
`
`Rl—CHg—‘S—H
`Rl—CHg—S—S—CHz—R2
`
`2
`R1_CH C
`2— || —O_CH2‘R
`0
`
`OH
`l
`1
`PhOSPhOTyl R —CH2—‘O“P—OH
`(H)
`
`Methyl
`
`Elhyl
`
`Phenyl
`
`Ester
`
`Chapter 3 Biomolecules
`
`59
`
`
`
`Figure 3—4 (a) Carbon atoms have a characteristic
`tetrahedral arrangement of their four single bonds
`which are about 0.154 nm long and at an angle of
`109.5° to each other. (b) Carbon—carbon single bonds
`
`7
`
`have freedom of rotation, shown for the compound
`ethane (OHS—0H3). (c) Carbon—carbon double
`bonds are shorter and do not allow free rotation.
`The single bonds on each doubly bonded carbon
`make an angle of 120° with each other. The two
`doubly bonded carbons and the atoms designated
`A, B, X, and Y all lie in the same rigid plane.
`
`l
`
`Figure 3—5 Some functional groups frequently en-
`countered in biomolecules. All groups are shown in
`their uncharged (un-ionized) form.
`
`p.3
`
`I
`
`p. 3
`
`

`

`————i
`
`60
`
`Part I Foundations of Biochemistry
`
`Many biomolecules are polyfunctional, containing two or more dif-
`ferent kinds of functional groups (Fig. 3—6), each with its own chemical
`characteristics and reactions. Amino acids, an important family of mol-
`ecules that serve primarily as monomeric subunits of proteins, contain
`at least two different kinds of functional groups: an amino group and a
`carboxyl group, as shown for histidine in Figure 3—6. The ability of an
`amino acid to condense (see Fig. 3—14e) with other amino acids to form
`proteins is dependent on the chemical properties of these two func-
`tional groups.
`
`COOH carboxyl
`H N (I: H
`2‘
`I
`ammo CH2
`C/N{'I
`H
`CH
`HC\N//
`
`imidazole
`
`phenyl
`
`Ill
`III
`alcohol
`methyl CH3 H OH C=C
`l
`/
`\
`\\N l
`_c—c—c\\
`//C——OH
`I'l/
`Ill
`Ill
`C—C hydroxyls
`III
`\OH
`
`s-amino
`
`Histidine
`
`Epinephrine
`
`0\\ O—CH3 methyl ester
`C/
`.
`l
`”mm
`H CflN\CH/(311—1
`Ii]:
`Iil
`methyl \
`\
`C C
`O
`CH+CH2\=X
`// — \\
`Il
`/
`CH—‘O—C—C\
`/CH
`CH /CH2
`ester
`C=C
`2
`l lH H
`
`phenyl
`
`Cocaine
`
`amino
`
`IIIHZ
`imidazole
`//N\C/C\N
`diphosphoryl
`methyl
`HC\
`(”3
`(EH
`OIH
`(l)H
`(EH3
`Ill
`amido
`amide
`N/ \N/
`HS-CHg—CH2—NH—fi—CHz—CHZ——NH—(fi—(lj—-(|3—CH2-—O—I”’——O—1|3l‘——O—CH2
`sulfhydryl
`0
`O OH CH3
`0
`O
`/0\ l
`
`HC H
`f
`methyl
`H CH
`hydroxyl
`I
`l /
`C——C
`I
`l
`(I)
`OH
`HO—P=O
`I
`OH
`
`.
`.
`.
`.
`Figure 3-6 Representatlve biomolecules With mul-
`tiple functional groups. Note that secondary (s) and
`tertiary (t) amino groups have, respectively, one
`and two of their amino hydrogens replaced by other
`groups.
`
`phosphoryl
`
`Coenzyme A
`
`Three-Dimensional Structure
`
`Although the covalent bonds and functional groups of biomolecules are
`central to their function, they do not tell the whole story. The arrange-
`ment in three-dimensional space of the atoms of a biomolecule is also
`crucially important. Compounds of carbon can often exist in two or
`more chemically indistinguishable three-dimensional forms, only one
`of which is biologically active. This specificity for one particular molec-
`ular configuration is a universal feature of biological interactions. All
`biochemistry is three-dimensional.
`
`p.4
`
`
`
`p. 4
`
`

`

`Chapter 3 Biomolecules
`
`61
`
`
`
`
`
`
`Figure 3—7 Models of the structure of the amino
`acid alanine. (a) Structural formula in perspective
`form. The symbol < represents a bond in which
`the atom at the wide end projects out of the plane
`of the paper, toward the reader; dashes represent
`a bond extending behind the plane of the paper.
`(b) Ball-and-stick model, showing relative bond
`lengths and the bond angles. The balls indicate the
`approximate size of the atomic nuclei. (c) Space-
`filling model, in which each atom is shown having
`its correct van der Waals radius (see Table 3—3).
`
`(a)
`
`(b)
`
`(c)
`
`Each Cellular Component Has a Characteristic
`Three-Dimensional Structure
`
`Biomolecules have characteristic sizes and three-dimensional struc-
`tures, which derive from their backbone structures and their substitu-
`ent functional groups. Figure 3—7 shows three ways to illustrate the
`three—dimensional structures of molecules. The perspective diagram
`specifies unambiguously the three—dimensional structure (stereochem-
`istry) of a compound. Bond angles and center-to-center bond lengths
`are best represented with ball-and-stick models, whereas the outer
`contours of molecules are better represented by space-filling models. In
`Space-filling models, the radius of each atom is proportional to its van
`der Waals radius (Table 3—3), and the contours of the molecule repre-
`sent the outer limits of the region from which atoms of other molecules
`are excluded.
`The three-dimensional conformation of biomolecules is of the ut-
`most importance in their interactions; for example, in the binding of a
`substrate (reactant) to the catalytic site of an enzyme (Fig. 3—8), the
`two molecules must fit each other closely, in a complementary fashion,
`for biological function. Such complementarity also is required in the
`binding of-a hormone molecule to its receptor on a cell surface, or in the
`recognition of an antigen by a specific antibody.
`The study of the three-dimensional structure of biomolecules with
`precise physical methods is an important part of modern research on
`cell structure and biochemical function. The most informative method
`is x—ray crystallography. If a compound can be crystallized, the diffrac-
`tion of x rays by the crystals can be used to determine with great
`precision the position of every atom in the molecule relative to every
`other atom. The structures of most small biomolecules (those with less
`than about 50 atoms), and of many larger molecules such as proteins,
`have been deduced by this means. X—ray crystallography yields a static
`picture of the molecule within the confines of the crystal. However,
`biomolecules almost never exist within cells as crystals; rather, they
`are dissolved in the cytosol or associated with some other component(s)
`0f the cell. Molecules have more freedom of intramolecular motion in
`solution than in a crystal. In large molecules such as proteins, the
`Small variations allowed in the three-dimensional structures of their
`monomeric subunits add up to extensive flexibility. Techniques such as
`nuclear magnetic resonance (NMR) spectroscopy complement x-ray
`Crystallography by providing information about the three-dimensional
`Structure of biomolecules in solution. Knowledge of the detailed three-
`dimensional structure of a molecule often sheds light on the mecha-
`nisms of the reactions in which the molecule participates.
`
`
`
`Table 3—3 van der Waals radii and covalent
`(single-bond) radii of some elements*
`
`Covalent radius
`van der Waals
`
`
` Element radius (nm) for single bond (nm)
`
`0.030
`0.1
`H
`0.074
`0.14
`O
`0.071
`0.14
`F
`0.073
`0.15
`N
`0.077
`0.17
`C
`0.103
`0.18
`S
`0.099
`0.18
`Cl
`0.110
`0.19
`P
`0.114
`0.20
`Br
`0.133
`0.22
`I
`
`
`* The van der Waals radius is about twice the covalent radius
`for each element. The distance between nuclei in a van der
`Waals interaction or a covalent bond is about equal to the sum
`of the values for the two atoms. Thus the length of a carbon—
`carbon single bond is about 0.077 + 0.077 = 0.154 nm.
`
`
`
`
`
`
`
`Figure 3—8 Complementary fit of a substrate mol-
`ecule to the active or catalytic site on an enzyme
`molecule. The enzyme shown here is chymotrypsin,
`an enzyme that acts in the intestine to degrade die-
`tary protein. Its substrate (shown in red) fits into a
`groove at the active site of the enzyme.
`
`p.5
`
`
`
`p. 5
`
`

`

`62
`
`Part I Foundations of Biochemistry
`
`Figure 3—9 Molecular asymmetry: chiral and
`achiral molecules. (a) When a carbon atom has four
`different substituent groups (A, B, X, Y), they can
`be arranged in two ways that represent nonsuper-
`imposable mirror images of each other (enantio-
`mers). Such a carbon atom is asymmetric and is
`called a chiral atom or chiral center. (b) When
`there are only three dissimilar groups around the
`carbon atom (i.e., the same group occurs twice),
`only one configuration in space is possible and the
`molecule is symmetric, or achiral. In this case the
`molecule is superimposable on its mirror image: the
`molecule on the left can be rotated counterclock-
`wise (when looking down its vertical bond from A
`to C) to create the molecule on the right.
`
`Most Biomolecules Are Asymmetric
`
`The tetrahedral arrangement of single bonds around a carbon atom
`confers on some organic compounds another property of great impor-
`tance in biology. When four different atoms or functional groups are
`bonded to a carbon atom in an organic molecule, the carbon atom is
`said to be asymmetric; it can exist in two different isomeric forms
`(stereoisomers) that have different configurations in space. A special
`class of stereoisomers, called enantiomers, are nonsuperimposable
`mirror images of each other (Fig. 3—9). The two enantiomers of a com-
`pound have identical chemical properties, but differ in a characteristic
`physical property, the ability to rotate the plane of plane-polarized
`light. A solution of one enantiomer rotates the plane of such light to the
`right, and a solution of the other, to the left. Compounds without an
`asymmetric carbon atom do not rotate the plane of plane-polarized
`light.
`
`¥_j.——_.—_._._..__—__—
`
`
`- Achiral
`
`Mirror -
`molecule:
`image of
`Rotated
`
`. molecule
`original
`
`
`molecule
`can be
`superimposed
`
`on mirror
`_
`image of
`
`Original
`_
`original
`
`molecule '
`'
`i
`
`'
`
`_ . Chiral
`| molecule:
`Rotated
`molecule
`cannot be
`superimposed
`on mirror
`image of
`original
`
`Mirror -
`image of
`original
`molecule
`
`
`
`
`
`
`
`
`'
`
`Original
`
`molecule
`
`
`
`
`
`Louis Pasteur
`1822—1895
`
`Louis Pasteur, in 1843, was the first to arrive at the correct expla-
`nation for this phenomenon of optical activity. Investigating the
`crystalline material that accumulated in Wine casks (“paratartaric
`acid,” also called racemic acid, from Latin racemus, “grape”), he had
`used a fine forceps to separate two types of crystals identical in shape,
`but mirror images of each other (Fig. 3—10). Both proved to have all of
`the chemical properties of tartaric acid, but one type rotated polarized
`light to the left, the other, to the right, but to the same extent. He later
`described the experiment and its interpretation:
`
`In isomeric bodies, the elements and the proportions in which they are
`combined are the same, only the arrangement of the atoms is different. .
`.
`.
`We know, on the one hand, that the molecular arrangements of the two
`tartaric acids are asymmetric, and, on the other hand, that these arrange-
`ments are absolutely identical, excepting that they exhibit asymmetry in
`opposite directions. Are the atoms of the dextro acid grouped in the form of
`a right-handed spiral, or are they placed at the apex of an irregular tetra-
`hedron, or are they disposed according to this or that asymmetric arrange-
`ment? We do not know.*
`
`* From Pasteur’s lecture to the Société Chimique de Paris in 1883, quoted in DuBos, R.
`(1976) Louis Pasteur: Free Lance of Science, p. 95, Charles Scribner’s Sons, New York.
`
`p.6
`
`
`
`p. 6
`
`

`

`Now we do know. X-ray crystallographic studies in 1951 confirmed
`that the levorotatory and dextrorotatory forms of tartaric acid are mir-
`ror images of each other, and established the absolute configuration of
`each (Fig. 3—10). The same approach has been used to demonstrate
`that the amino acid alanine exists in two enantiomeric forms (Chapter
`5)_ The central carbon atom of the alanine molecule is bonded to four
`different substituent groups: a methyl group, an amino group, a car-
`boxyl group, and a hydrogen atom. The two stereoisomers of alanine
`are nonsuperimposable mirror images of each other, and thus are
`enantiomers.
`Compounds with asymmetric carbon atoms can be regarded as oc-
`curring in left- and right-handed forms, and are therefore called chiral
`compounds (Greek chiros, “hand”). Correspondingly, the asymmetric
`atom or center of chiral compounds is called the chiral atom or chiral
`center (Fig. 3—9). All but one of the 20 amino acids have chiral cen-
`ters; glycine is the exception.
`More generally, variations in the three-dimensional structure of
`biomolecules are described in terms of configuration and conformation.
`These terms are not synonyms. Configuration denotes the spatial
`arrangement of an organic molecule that is conferred by the presence
`of either (1) double bonds, around which there is no freedom of rotation,
`or (2) chiral centers, around which substituent groups are arranged in
`a specific sequence. The identifying characteristic of configurational
`isomers is that they cannot be interconverted without breaking one or
`more covalent bonds.
`Figure 3—11a shows the configurations of maleic acid, which occurs
`in some plants, and its isomer fumaric acid, an intermediate in sugar
`metabolism. These compounds are geometric or cis-trans isomers;
`they differ in the arrangement of their substituent groups with respect
`to the nonrotating double bond. Maleic acid is the cis isomer and fu-
`maric acid the trans isomer; each is a well—defined compound that can
`be isolated and purified. These two compounds are stereoisomers but
`not enantiomers; they are not mirror images of each other.
`
`/H
`H\
`/C=C\
`
`COOH
`HOOC
`Maleic acid (cis)
`
`(a)
`
`HOOC\
`/H
`/C: :C\
`
`COOH
`H
`Fumaric acid (trans)
`
`CH:a CH“
`.
`
`11
`10
`i' I\\- 12
`
`0st | 9
`
`CH,
`
`Off}.
`/
`0/ \H
`
`Chapter 3 Biomolecules
`
`63
`
`1
`4
`Hooc\z Vcoon
`[IO—CV
`HOH Hon
`
`2R,3R-Tartaric acid
`(dextrorotatory)
`
`1
`4
`HOOC\2 VCOOH
`4043s.
`HOH
`\OIlI-I
`28,3S-Tartaric acid
`(levorotatory)
`
`Figure 3—10 Pasteur separated crystals of two
`stereoisomers of tartaric acid and showed that solu-
`tions of the separated forms each rotated polarized
`light to the same extent but in opposite directions.
`Pasteur’s dextrorotatory and levorotatory forms
`were later shown to be the R,R and 8,8 isomers
`shown here. For compounds with more than one
`chiral center, the RS system of nomenclature is
`often more useful than the D and L system de-
`scribed in Chapter 5. In the RS system, each group
`attached to a chiral carbon is assigned a priority.
`The priorities of some common substituents are:
`—-OCH2 > —OH > —NH2 > —COOH > —CHO >
`—CH20H > —CH3 > ——H. The chiral carbon atom
`is viewed with the group of lowest priority pointing
`away from the viewer. If the priority of the other
`three groups decreases in counterclockwise order,
`the configuration is S; if in clockwise order, R. In
`this way each chiral carbon is designated as either
`R or S, and the inclusion of these designations in
`the name of the compound provides an unambigu-
`ous description of the stereochemistry at each
`chiral center.
`
`Figure 3—11 Configurations of stereoisomers.
`(a) Isomers such as maleic acid and fumaric acid
`cannot be interconverted without breaking covalent
`bonds, which requires the input of much energy.
`(b) In the vertebrate retina, the initial event in
`light detection is the absorption of visible light by
`11-cis-retinal. The energy of the absorbed light
`(about 250 kJ/mol) converts 11-cis-retinal to all-
`trans-retinal, triggering electrical changes in the
`retinal cell that lead to a nerve impulse.
`
`1 Leis-Retinal
`
`All-trans-Retinal
`
`
`
`p. 7
`
`

`

`
`
`
`
`
`
`Potentialenergy(kJ/mol)
`
`12
`
`8 "
`4 I—
`0 _
`
`
`
`gitfléojt£
`
`12.1
`kJ/mol
`
`‘1’
`
`g
`
`I—
`
`0
`
`_L
`60
`
`I_ _l
`__J_
`180
`240
`120
`Torsion angle (degrees)
`
`1__ _|_
`300
`360
`
`
`
`Eclipsed
`
`Staggered
`
`Figure 3—12 Many conformations of ethane are
`possible because of freedom of rotation around the
`carbon—carbon single bond. When the front carbon
`atom (as viewed by the reader) and its three at-
`tached hydrogens are rotated relative to the rear
`carbon atom, the potential energy of the molecule
`rises in the fully eclipsed conformation (torsion
`angle 0°, 120°, etc.), then falls in the fully staggered
`conformation (torsion angle 60°, 180°, etc.). .The en-
`ergy differences are small enough to allow rapid
`interconversion of the two forms (millions of times
`per second), thus the eclipsed and staggered forms
`cannot be isolated separately.
`
`Figure 3—13 Stereoisomers that are distinguished
`by sensory receptors for smell and taste in humans.
`(a) 'IVvo stereoisomers of carvone, designated R and
`S (see Fig. 3—10, legend). R-carvone (from spear-
`mint oil) has the characteristic fragrance of spear-
`mint; S-carvone (from caraway seed oil) smells like
`caraway. (b) Aspartame, the artificial sweetener
`sold under the trade name NutraSweet, is easily
`distinguishable by taste from its bitter-tasting
`stereoisomer, although the two differ only in the
`configuration about one of the two chiral carbon
`atoms (in red).
`
`‘EHa
`O\?/C\C|3H
`H2C\C/CH2
`CHs—fill H
`CH2
`R-Carvone
`(Spearmint)
`
`s3
`O\$/C\$H
`H2C\C/CH2
`H’ \(lj=CH2
`CH3
`S—Carvone
`(caraway)
`
`Molecular conformation refers to the spatial arrangement of sub-
`stituent groups that are free to assume different positions in space,
`without breaking any bonds, because of the freedom of bond rotation.
`In the simple hydrocarbon ethane, for example, there is nearly com-
`plete freedom of rotation around the carbon—carbon single bond. Many
`different, interconvertible conformations of the ethane molecule are
`therefore possible, depending upon the degree of rotation (Fig. 3-12).
`Two conformations are of special interest: the staggered conformation,
`which is more stable than all others and thus predominates, and the
`eclipsed form, which is least stable. It is not possible to isolate either of
`these conformational forms, because they are freely interconvertible
`and in equilibrium with each other. However, when one or more of the
`hydrogen atoms on each carbon is replaced by a functional group that
`is either very large or electrically charged, freedom of rotation around
`the carbon—carbon single bond is hindered. This limits the number of
`stable conformations of the ethane derivative.
`
`Interactions between Biomolecules Are Stereospecific
`
`Many biomolecules besides amino acids are chiral, containing one or
`more asymmetric carbon atoms. The chiral molecules in living organ-
`isms are usually present in only one of their chiral forms. For example,
`the amino acids occur in proteins only as the L isomers. Glucose, the
`monomeric subunit of starch, has five asymmetric carbons, but occurs
`biologically in only one of its chiral forms, the D isomer. (The conven-
`tions for naming stereoisomers of the amino acids are described in
`Chapter 5; those for sugars, in Chapter 11). In contrast, when a com-
`pound having an asymmetric carbon atom is chemically synthesized in
`the laboratory, the nonbiological reactions usually produce all possible
`chiral forms in an equimolar mixture that does not rotate polarized
`light (a racemic mixture). The chiral forms in such a mixture can be
`separated only by painstaking physical methods. Chiral compounds in
`living cells are produced in only one chiral form because the enzymes
`that synthesize them are also chiral molecules.
`Stereospecificity, the ability to distinguish between stereoiso-
`mers, is a common property of enzymes and other proteins and a char-
`acteristic feature of the molecular logic of living cells. If the binding
`site on a protein is complementary to one isomer of a chiral compound,
`it will not be complementary to the other isomer, for the same reason
`that a left glove does not fit a right hand. Two striking examples of the
`ability of biological systems to distinguish stereoisomers are shown in
`Figure 3—13.
`
`‘000
`
`+NH3
`0’0
`(PH 3
`\CH2/ \c/ \,C: \OCH3
`c“)
`(IJH2 H
`Hfi/ §(|3H
`HC\C/CH
`H
`
`C
`
`'000
`
`+NH3
`0/0
`(5‘11 E
`\CH2/ \0/ \C: \OCH3
`(H) H
`(IJH
`Hfi/ \CfH
`HC\C/CH
`H
`
`C
`
`L—Aspartyl-L-phenylalanyl methyl ester
`(aspartame) (sweet)
`
`L—Aspartyl-D-phenylalanyl methyl ester
`(bitter)
`
`(a)
`
`(b)
`
`64
`
`p.8
`
`
`p. 8
`
`