Table of Contents

. . . . . . . . . . . . . . . . . . . . . . . .

Part I: Molecular Components of the Cell

Chapter 1: Chemistry Is the Logic of Biological Phenomena 1

Chapter 2: Water: The Medium of Life 11

Chapter 3: Thermodynamics of Biological Systems 29

Chapter 4: Amino Acids 43

Chapter 5: Proteins: Their Primary Structure and Biological Functions 61

Chapter 6: Proteins: Secondary, Tertiary, and Quaternary Structure 77

Chapter 7: Carbohydrates and the Glycoconjugates of the Cell Surfaces 92

Chapter 8: Lipids 111

Chapter 9: Membranes and Membrane Transport 126

Chapter 10: Nucleotides and Nucleic Acids 142

Chapter 11: Structure of Nucleic Acids 158

Chapter 12: Recombinant DNA: Cloning and Creation of
Chimeric Genes
174
Part II: Protein Dynamics

Chapter 13: Enzyme--Kinetics and Specificity 187

Chapter 14: Mechanisms of Enzyme Action 211

Chapter 15: Enzyme Regulation 223

Chapter 16: Molecular Motors 242

Part III: Metabolism and Its Regulation

Chapter 17: Metabolism--An Overview 255

Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
2
Chapter 18: Glycolysis 277

Chapter 19: The Tricarboxylic Acid Cycle 295

Chapter 20: Electron Transport and Oxidative Phosphorylation 309

Chapter 21: Photosynthesis 328

Chapter 22: Gluconeogenesis, Glycogen Metabolism, and the Pentose Phosphate
Pathway
346

Chapter 23: Fatty Acid Catabolism 369

Chapter 24: Lipid Biosynthesis 384

Chapter 25: Nitrogen Acquisition and Amino Acid Metabolism 403

Chapter 26: The Synthesis and Degradation of Nucleotides 420

Chapter 27: Metabolic Integration and Organ Specialization 434

Part IV: Information Transfer

Chapter 28: DNA Metabolism: Replication, Recombination, and Repair 449

Chapter 29: Transcription and the Regulation of Gene Expression 467

Chapter 30: Protein Synthesis 482

Chapter 31: Completing the Protein Life Cycle: Folding, Processing and
Degradation
501

Chapter 32: The Reception and Transmission of Extracellular Information 509

Glossary

525


Chapter 1
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Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
3


Preface

. . . . . . . . . . . . . . . . . . . . . . . .


In one scene in the movie Stripes (Columbia Picture Corporation 1981), privates
John Winger and Russell Zissky (played by Bill Murray and Harold Ramis) attempt to
persuade their platoon to an all-night training session to prepare for the next days
final parade. The troops are skeptical of the plan; however, Zissky wins them over by
his testimony of the importance of cramming. He proudly reports that he had, in fact,
once learned two semesters of geology in a single three-hour all-nighter.
It would seem unlikely that this approach would work well with biochemistry (or
even geology). Rather a steady diet of reading, problem solving, and reviewing might
be a better plan of attack. This study guide was written to accompany Biochemistry,
Third Edition by Garrett and Grisham. It includes chapter outlines, guides to key
points covered in the chapters, in-depth solutions to the problems presented in the
textbook, additional problems, and detailed summaries of each chapter. In addition,
there is a glossary of biochemical terms and key text figures.
Several years ago I spent part of a sabbatical in Italy and, in preparation, took a
year-long course in elementary Italian. I had not been on the student-end of an
academic interaction for several years and taking a language course was an excellent
opportunity to be reminded of the difficulties of learning something for the first time.
Memorization is part and parcel to the study of any language and so I found myself
committing to memory nouns, verbs, adverbs, adjectives, and complex, irregular verb
conjugations. The study of biochemistry has parallels to language studies in that
memorization is necessary. What makes the study of biochemistry somewhat easier,
however, are the common themes, the interconnections between various facets of
biochemistry, and the biological and chemical principles at work. The authors have
done a marvelous job in presenting these aspects of biochemistry and I have
attempted to highlight them here. Biochemistry is a demanding discipline but one
well worth the effort for any student of the sciences. Buona fortuna.

Acknowledgments
It is often stated that teaching a subject is the best way to learn it. In teaching my
one-semester biochemistry course at Vassar College, because there is never sufficient
time to cover all the topics, I used to worry about forgetting certain aspects of
biochemistry. Thanks to Charles Grisham and Reginald Garrett, this fear is no longer
with me. I thank both authors for the marvelous text and the opportunity to relearn
all of biochemistry. I also thank my co-author Steven Theg. Alyssa White, Sandi
Kiselica Lisa Weber, and Jennifer Risden of Brooks/Cole, a division of Thomson Higher
Education, were very helpful and I thank them. To my wife Kristen and my two sons
Tristan and Kaedin I give special thanks for putting up with me during this project.



David K. Jemiolo
Poughkeepsie, NY
February 2004
Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
4

Acknowledgments
In working on this text I have learned anew that it is a pleasure to have the
opportunity to think deeply about the fundamentals of biochemistry, the subject I both
teach and use in my daily research. Some topics are surely what they appear to be on
the surface, but many more are rather like onions; in peeling away a layer you find
another, and then another, so that each new insight raises numerous new questions
not imagined before. I thank Charles Grisham and Reginald Garrett for crafting such a
well-written text with which to make this intellectual journey.
I am grateful to my co-author, Davi d J emi ol o, for hi s hard, hard work on thi s
revi si on, and for hi s steady hand al l throughout the project. I al so thank Al yssa Whi te
of Brooks/Col e, a di vi si on of Thomson Hi gher Educati on, for her constant
encouragement. Fi nal l y, I thank J i l l and our three sons, Chri s, Al ex and Sam for thei r
unvaryi ng support. Wi thout them l i ttl e of what I do woul d seem much worth doi ng.

Steven M. Theg
Davis, CA
February 2004
Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
5
Why study biochemistry?
This excerpt from Poetry and Science by the Scottish poet Hugh MacDiarmid (1892
1978), which first appeared in Lucky Poet (1943), might help with an answer.


Poetry and Science


...
Wherefore I seek a poetry of facts. Even as
The profound kinship of all living substance
Is made clear by the chemical route.
Without some chemistry one is bound to remain
Forever a dumbfounded savage
In the face of vital reactions.
The beautiful relations
Shown only by biochemistry
Replace a stupefied sense of wonder
With something more wonderful
Because natural and understandable.
Nature is more wonderful
When it is at least partly understood.
Such an understanding dawns
On the lay reader when he becomes
Acquainted with the biochemistry of the glands
In their relation to diseases such as goitre
And their effects on growth, sex, and reproduction.
He will begin to comprehend a little
The subtlety and beauty of the action
Of enzymes, viruses, and bacteriophages,
These substances which are on the borderland
Between the living and the non-living.
He will understand why the biochemist
Can speculate on the possibility
Of the synthesis of life without feeling
That thereby he is shallow or blasphemous.
He will understand that, on the contrary,
He finds all the more
Because he seeks for the endless
---'Even our deepest emotions
May be conditioned by traces
Of a derivative of phenanthrene!'
















Scienceis the
Differential Calculus
of themind,
Art is theIntegral
Calculus; they may be
Beautiful apart, but
aregreat only when
combined.

Sir Ronald Ross












Comments, corrections, and suggestions may be directed to GGGuide@Vassar.edu.

Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
6

Chapter 1


Chemistry Is the Logic of
Biological Phenomena


. . . . . . . . . . . . . . . . . . . . . . . .

Chapter Outline

v Properties of living systems
Highly organized - Cells > organelles > macromolecular complexes > macromolecules
(proteins, nucleic acids, polysaccharides)
Structure/function correlation
Energy transduction: ATP and NADPH energized molecules
Steady state by virtue of energy flow
Self-replication and importance of structural complementarity
v Biomolecules
Elements: Hydrogen, oxygen, carbon, nitrogen (lightest elements of the periodic table
capable of forming a variety of strong covalent bonds)
- Carbon -4 bonds, Nitrogen -3 bonds, Oxygen 2 bonds, Hydrogen -one covalent
bond
Compounds: Carbon-based compounds -versatile
v Biomolecular hierarchy
Simple compounds: H
2
O, CO
2
, NH
4
+
, NO
3
-
, N
2

Metabolites
Building blocks: Amino acids, nucleotides, monosaccharides, fatty acids, glycerol
Macromolecules: Proteins, nucleic acids, polysaccharides, lipids
Supramolecular complexes: Ribosomes, chromosomes, cytoskeleton
v Membranes: Lipid bilayers with membrane proteins
v Organelles: Mitochondria, chloroplasts, nuclei, endoplasmic reticulum, Golgi, etc.
v Cells: Fundamental units of life
v Properties of biomolecules
Directionality or structural polarity
- Proteins: N-terminus and C-terminus
- Nucleic acids: 5- and 3- Ends
- Polysaccharides: Reducing and nonreducing ends
Information content: Sequence of monomer building blocks and 3-dimensional
architecture
v 3-Dimensional architecture and intermolecular interactions (via complementary surfaces) of
macromolecular are based on weak forces
van der Waals interactions (London dispersion forces)
Hydrogen bonding
Ionic interactions
Hydrophobic interactions
Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
7
v Life restricted to narrow range of conditions (temperature, pH, salt concentration, etc.) because of
dependence on weak forces. Denaturation: Loss of structural order in a macromolecule
v Enzymes: Biological catalysts capable of being regulated
v Cell types
Prokaryotes: Eubacteria and archaea: Plasma membrane but no internal membrane-
defined compartments
- Archaea include thermoacidophiles, halophiles and methanogens
Eukaryotes: Internal membrane-defined compartments: nuclei, endoplasmic recticulum,
Golgi, mitochondria, chloroplasts, vacuoles
Viruses and bacteriophages: Incomplete genetic systems

Chapter Objectives

Understand the basic chemistry of H, O, N and C.
H forms a single covalent bond. When bound to an electronegative element, like O or N, the
electron pair forming the covalent bond is not equally shared, giving rise to a partial positive
charge on the hydrogen (this is the basis of H bonds which will be covered in the next chapter).
In extreme cases the H can be lost as a free proton.
O forms two covalent bonds and has two lone pairs of electrons. It is an electronegative
element and when bound to hydrogen it will cause H to be partially positively charged. O is
highly reactive due to its high electronegativity.
N forms up to three covalent bonds and has a single lone pair of electrons. It is an
electronegative element and will create a partial positive charge on a hydrogen bonded to it.
C forms four covalent bonds. With four single bonds, tetrahedral geometry is predominant.
With one double bond, carbon shows trigonal planar geometry, with an additional pair of
electrons participating in a pi bond.

Macromolecules and subunits
Proteins are formed from amino acids composed of C, H, O, N and in some instances S.

Nucleic acids are formed from nucleotides that are composed of phosphate, sugar and
nitrogenous base components. (Nucleosides lack phosphate).

Polysaccharides are made of carbohydrates or sugar molecules.

Lipids are a class of mostly nonpolar, mostly hydrocarbon molecules.

Macromolecular structures
Macromolecular structures are composed of complexes of macromolecules (i.e., proteins,
nucleic acids, polysaccharides and lipids). The ribosome, made up of protein and ribonucleic
acid, is a prime example.

Organelles
Organelles are subcellular compartments defined by lipid bilayer membranes.

Cell types
There are two fundamental cell types: eukaryotic, having organelles and a defined nuclear
region, and prokaryotic, lacking organelles and a membrane-enclosed region of genetic material.
The archaea and eubacteria comprise the prokaryotes.

Problems and Solutions

1. The nutri ti onal requi rements of Escherichia coli cel l s are far si mpl er than those of
humans, yet the macromol ecul es found i n bacteri a are about as compl ex as those of
ani mal s. Because bacteri a can make al l thei r essenti al bi omol ecul es whi l e subsi sti ng on
Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
8
a si mpl er di et, do you t hi nk bacteri a may have more bi osyntheti c capaci ty and hence
more metabol i c compl exi ty than ani mal s? Organi ze your thoughts on thi s questi on, pro
and con, i nto a rati onal argument.

Answer: Although it is true that Escherichia coli are capable of producing all of their essential
biomolecules (e.g., there is no minimum daily requirement for vitamins in the world of wild-type
E. coli), they are rather simple, single-cell organisms capable of a limited set of responses. They
are self sufficient, yet they are incapable of interactions leading to levels of organization such as
multicellular tissues. Multicellular organisms have the metabolic complexity to produce a
number of specialized cell types and to coordinate interactions between them.

2. Wi thout consul ti ng fi gures i n thi s chapter, sketch the characteri sti c prokaryoti c and
eukaryoti c cel l types and l abel thei r perti nent organel l e and membrane systems.

Answer: Prokaryotic cells lack the compartmentation characteristic of eukaryotic cells and are
devoid of membrane bound organelles such as mitochondria, chloroplasts, endoplasmic
reticulum, Golgi apparatus, nuclei, and vacuoles. Both cell types are delimited by membranes
and contain ribosomes.

3. Escherichia coli cel l s are about 2 m (mi crons) l ong and 0.8 m i n di ameter.
a. How many E. coli cel l s l ai d end to end woul d fi t across the di ameter of a pi nhead?
(Assume a pi nhead di ameter of 0.5 mm.)

Answer:

E. coli/pinhead diameter =
0.5 mm/dia.
2 m/E. coli
=
0.510
3
m
210
-6
m
= 250 E. coli/pinhead diameter


b. What i s the vol ume of an E. coli cel l ? (Assume i t i s a cyl i nder, wi th the vol ume of a
cyl i nder gi ven by V=r
2
h, where =3.14.)

Answer:

V = r
2
h
= 3.14 (
0.8 m
2
)
2
2 m
= 3.14 (0.4 10
6
m)
2
(2 10
6
m)
= 1 18
18
m
3
But, 1 m
3
= (10
2
cm)
3
= 10
6
cm
3
= 10
6
ml = 10
3
L
V = 1 10
-18
m
3
= 1 10
-15
L
= 1 fL (femtoliter)


c. What i s the surface area of an E. coli cel l ? What i s the surface-to-vol ume rati o of an
E. coli cel l ?

Answer:
Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
9

SA = 2 r
2
+ dh
= 2 3.14 (0.4 10
6
m)
2
+ 3.14 (0.8 10
6
m)(2 10
6
m)
= 6 10
12
m
2
SA/V = 6 10
12
m
2
= 6 10
6
m
-1





d. Gl ucose, a major energy-yi el di ng nutri ent, i s present i n bacteri al cel l s at a
concentrati on of about 1 mM. What i s the concentrati on of gl ucose, expressed as
mg/ml ? How many gl ucose mol ecul es are contai ned i n a typi cal E. coli cel l ? (Recal l that
Avogadros number =6.023 x 10
23
.)

Answer:


[Glucose] = 1 mM = 110
-3
mole/liter
Glucose = C
6
H
12
O
6
Mr = 612 +121.0+616
= 180
[Glucose] = 110
-3
mole
liter
180
g
mole
[Glucose] = 0.18
g
L
= 0.18
mg
ml




moles glucose = concentration volume
= 1 mM 1 10
-15
L (from b.)
= 1 10
-18
moles
# molecules = 1 10
-18
moles 6.023 10
23
(molecule/mol)
= 6 10
5
molecules


e. A number of regul atory protei ns are present i n E. coli at onl y one or two mol ecul es
per cel l . If we assume that an E. col i contai ns just one mol ecul e of a parti cul ar protei n,
what i s the mol ar concentrati on of thi s protei n i n the cel l ? If the mol ecul ar wei ght of
thi s protei n i s 40 kD, what i s i ts concentrati on, expressed as mg/ml ?

Answer:
Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
10

1 molecule
6.023 10
23
molecules/mole
= 1.7 10
-24
mole
Molar concentration =
moles
volume(in liters)
=
1.7 10
-24
mole
10
-15
L (from b.)
= 1.7 10
-9
M = 1.7 nM



[Protein] =1.710
-9
mole
L
4010
3
g
mole
= 6.810
-5
g
L
= 6.810
-5
mg
ml


f. An E. coli cel l contai ns about 15,000 ri bosomes, whi ch carry out protei n synthesi s.
Assumi ng ri bosomes are spheri cal and have a di ameter of 20 nm (nanometers), what
fracti on of the E. coli cel l vol ume i s occupi ed by ri bosomes?







Answer:


volume of one ribosome =
4
3
r
3
=
4
3
3.14 (10 10
9
m)
3
= 4.2 10
-24
m
3


volume of 15, 000 ribosomes = 4.2 10
-24
m
3
15, 000
= 6.3 10
20
m
3
fractional volume = volume ribosome/volume E. coli
=
6.3 10
20
m
3
1 10
18
m
3
(from b.)
= 0.063 or 6.3%


g. The E. coli chromosome i s a si ngl e DNA mol ecul e whose mass i s about 3.0 x 10
9
dal tons. Thi s macromol ecul e i s actual l y a ci rcul ar array of nucl eoti de pai rs. The
average mol ecul ar wei ght of a nucl eoti de pai r i s 660 and each pai r i mparts 0.34 nm to
the l ength of the DNA mol ecul e. What i s the total l ength of the E. coli chromosome?
How does thi s l ength compare wi th the overal l di mensi ons of an E. coli cel l ? How many
nucl eoti de pai rs does thi s DNA contai n? The average E. coli protei n i s a l i near chai n of
360 ami no aci ds. If three nucl eoti de pai rs i n a gene encode one ami no aci d i n a protei n,
how many di fferent protei ns can the E. coli chromosome encode? (The answer to thi s
questi on i s a reasonabl e approxi mati on of the maxi mum number of di fferent ki nds of
protei ns that can be expected i n bacteri a.)

Answer: The number of moles of base pairs in 3.1 x 10
9
D dsDNA is given by
Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
11

=
3.010
9
(gm/mole dsDNA)
660(gm/mole bp)
= 4.5510
6
mole bp/mole
1 molecule dsDNA = 4.5510
6
mole bp/mole
length = 4.5510
6
mole bp/mole0.34 (nm/bp)
=1.5510
3
m =1.55 mm = 1,550 m
length E. coli = 2mm
length DNA
length E. coli
=
1,550 mm
2mm
= 775


To calculate the number of different proteins:

360 aa/protein 3 bp/aa = 1080 bp/protein
# different proteins =
4.55 10
6
bp
1080 bp/protein
= 4, 213 proteins


4. Assume that mi tochondri a are cyl i nders 1.5 m i n l ength and 0.6 m i n di ameter.
a. What i s the vol ume of a si ngl e mi tochondri on?







Answer:

V = r
2
h
= 3.14 (3 10
-7
m)
2
1.5 10
6
m
= 4.24 10
6
m
3
(1 m
3
= 10
3
L)
= 4.24 10
16
L = 0.424 fL


b. Oxal oacetate i s an i ntermedi ate i n the ci tri c aci d cycl e, an i mportant metabol i c
pathway l ocal i zed i n the mi tochondri a of eukaryoti c cel l s. The concentrati on of
oxal oacetate i n mi tochondri a i s about 0.03 M. How many mol ecul es of oxal oacetate
are i n a si ngl e mi tochondri on?

Answer:

# molecules = molar conc. volume 6.023 10
23
molecules/mol
= (0.03 10
-6
)(4.24 10
-16
)(6.023 10
23
)
= 7.66 molecules (less than 8 molecules)


5. Assume that l i ver cel l s are cuboi dal i n shape, 20 m on a si de.
a. How many l i ver cel l s l ai d end to end woul d fi t across the di ameter of a pi n head?
(Assume a pi nhead di ameter of 0.5 mm.)
Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
12

Answer:

# liver cells =
0.5 (mm/pinhead)
20( m/cell)
=
0.5 10
-4
(m/pinhead)
20 10
-6
(m/cell)
= 25 cells


b. What i s the vol ume of a l i ver cel l ? (Assume i t i s a cube.)

Answer:

Volume of cube = length
3
= (2010
6
m)
3
= 810
-15
m
3

100cm
m






3

1L
1000cm
3








= 810
-12
L = 8pL


c. What i s the surface area of a l i ver cel l ? What i s the surface-to-vol ume rati o of a l i ver
cel l ? How does thi s compare to the surface-to-vol ume rati o of an E. coli cel l ? (Compare
thi s answer to that of probl em 3c.) What probl ems must cel l s wi th l ow surface-to-vol ume
rati os confront that do not occur i n cel l s wi th hi gh surface-to-vol ume rati os?

Answer:

Surface area = 6(2010
-6
m)(2010
-6
m) = 2.410
-9
m
2
Surface area
Volume
=
2.4 10
-9
m
2
810
-15
m
3
= 3.010
5
m
-1


The surface-to-volume ratio of liver to that of E. coli is given by:

3.0 10
5
m
-1
6 10
-6
m
-1
= 0.05 (1/20th)
The volume of a cell sets or determines the cell's maximum metabolic activity while the surface
area defines the surface across which nutrients and metabolic waste products must pass to
meet the metabolic needs of the cell. Cells with a low surface-to-volume ratio have a high
metabolic capacity relative to the surface area for exchange.

d. A human l i ver cel l contai ns two sets of 23 chromosomes, each set bei ng roughl y
equi val ent i n i nformati on content. The total mass of DNA contai ned i n these 46
enormous DNA mol ecul es i s 4 x 10
12
dal tons. Because each nucl eoti de pai r contri butes
660 dal tons to the mass of DNA and 0.34 nm to t he l ength of DNA, what i s the total
number of nucl eoti de pai rs and the compl ete l ength of the DNA i n a l i ver cel l ? How does
thi s l ength compare wi th the overal l di mensi ons of a l i ver cel l ? The maxi mal
i nformati on i n each set of l i ver cel l chromosomes shoul d be rel ated to the number of
nucl eoti de pai rs i n the chromosome sets DNA. Thi s number can be obtai ned by di vi di ng
the total number of nucl eoti de pai rs cal cul ated above by 2. What i s thi s val ue? If thi s
i nformati on i s expressed i n protei ns that average 400 ami no aci ds i n l ength and three
nucl eoti de pai rs encode one ami no aci d i n a protei n, how many di fferent ki nds of
protei ns mi ght a l i ver cel l be abl e to produce? (In real i ty l i vers cel l s express at most
about 30,000 di fferent protei ns. Thus, a l arge di screpancy exi sts between the
theoreti cal i nformati on content of DNA i n l iver cel l s and the amount of i nformati on
actual l y expressed.)

Answer:
Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
13

# base pairs =
4.0 10
12
D
660 D/bp
= 6.110
9
bp
length = 0.34(nm/bp) 6.110
9
bp
= 2.06 m!
length relative to liver cell =
2.06 m
2 m
= 1.05 10
5
or about 100, 000 times greater!


The information content = 3.0 10
9
# different proteins = 400 (aa/protein) 3 (bp/aa) = 1200 bp/protein
# different proteins =
3.0 10
9
1200 (nt/protein)
= 2.5 10
6
proteins


6. Bi omol ecul es i nteract wi th one another through mol ecul ar surfaces that are
structural l y compl ementary. How can vari ous protei ns i nteract wi th mol ecul es as
di fferent as si mpl e i ons, hydrophobi c l i pi ds, pol ar but uncharged carbohydrates, and
even nucl ei c aci ds?

Answer: The amino acid side chains of proteins can participate in a number of interactions
through hydrogen bonding, ionic bonding, hydrophobic interactions, and van der Waals
interactions. For example, the polar amino acids, acidic amino acids and their amides, and the
basic amino acids all have groups that can participate in hydrogen bonding. Those amino acid
side chains that have net charge can form ionic bonds. The hydrophobic amino acids can
interact with nonpolar, hydrophobic surfaces of molecules. Thus, amino acids are capable of
participating in a variety of interactions. A protein, can be folded in three dimensions to
organize amino acids into surfaces with a range of properties.

7. What structural features al l ow bi ol ogi cal pol ymers to be i nformati onal macro-
mol ecul es? Is i t possi bl e for pol ysacchari des to be i nformati onal macromol ecul es?

Answer: Biopolymers like proteins and nucleic acids are informational molecules because they
are vectorial molecules, composed of a variety of building blocks. For example, proteins are
linear chains of some 20 amino acids joined head-to-tail to produce a polymer with distinct
ends. The information content is the sequence of amino acids along the polymer. Nucleic acids
(DNA and RNA) are also informational molecules for the same reason. Here, the biopolymer is
made up of 4 kinds of nucleotides. Monosaccharides are capable of forming polymeric
structures but typically with little information content. When a polymer is formed from only one
kind of monosaccharide, as for example in glycogen, starch, and cellulose, even though the
molecule is vectorial (i.e., it has distinct ends) there is little information content. (The
polysaccharides have an advantage in chemistry over the nucleic acids and proteins in that they
readily form branch structures. Branched polysaccharides composed of a number of different
monosaccharides are rich in information.)

8. Why i s i t i mportant that weak forces, not strong forces, medi ate bi omol ecul ar
recogni ti on i nteracti ons?

Chapter 1
.
Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
14
Answer: Life is a dynamic process characterized by continually changing interactions.
Complementary interactions based on covalent bonding would of necessity produce static
structures, structures difficult to change and slow to respond to outside stimuli.

9. What i s the di stance between the centers of two carbon atoms (thei r l i mi t of
approach) that are i nteracti ng through van der Waal s forces? What i s the di stance
between the centers of two carbon atoms joi ned i n a coval ent bond? (See Tabl e 1.4)

Answer: The limit of approach of two atoms is determined by the sum of their van der Waals
radii, which are given in Table 1.4. For two carbon atoms the limit of approach is (0.17 nm +
0.17 nm) 0.34 nm. The distance between the centers of two carbon atoms joined in a covalent
bond is the sum of the covalent radii of the two carbons or (0.077 nm + 0.077 nm) 0.154 nm.
Clearly, two carbons sharing electrons in a covalent bond are closer together than are two
carbons interacting through van der Waals forces.

From the formula for the van der Waals interaction energy given in Figure 1.13, the distance at
which the interaction energy is zero can be calculated by setting the equation equal to zero and
solving for r, which in this case is the sum of the van der Waals radii. The distance is 0.353 nm
or 0.176 nm per atom.

From the same equation one can determine the distance at which the van der Waals force is at a
low point by taking the first derivative of U with respect to r, setting it equal to zero and solving
for r. In this case r equals 0.396 nm or 0.198 per atom.

10. Why does the central rol e of weak forces i n bi omol ecul ar i nteracti ons restri ct l i vi ng
systems to a narrow range of envi ronmental condi ti ons?

Answer: The weak forces such as hydrogen bonds, ionic bonds, hydrophobic interactions, and
van der Waals interactions can be easily overcome by low amounts of energy. Slightly elevated
temperatures are sufficient to break hydrogen bonds. Changes in ionic strength, pH,
concentration of particular ions, etc., all potentially have profound effects on macromolecular
structures dependent on the weak forces.

11. Descri be what i s meant by the phrase "cel l s are steady-state systems".

Answer: Life is characterized as a system through which both energy and matter flow. The
consequence of energy flow in this case is order, the order of monomeric units in biopolymers,
which in turn produce macromolecular structures that function together as a living cell.

12. Bi ol ogi cal mol ecul es often i nteract vi a weak forces (H bonds, van der Waal s
i nteracti ons, etc.). What woul d be the effect of an i ncrease i n ki netic energy on such
interacti ons?

Answer: Weak forces are easily disrupted by increases in the kinetic energies of the interacting
components. Thus, slight increases in temperature can disrupt weak forces. Biological
molecules, like proteins whose three-dimensional structures are often determined by weak force
interactions, may undergo conformational changes even with modest changes in temperature
leading to inactivation or loss of function.

13. Protei ns and nucl ei c aci ds are i nformati onal macromol ecul es. What are the two
mi ni mal cri teri a for a l i near i nformati onal pol ymer?

Answer: Informational macromolecules must be directional (vectorial) and they must be
composed of unique building blocks. Both nucleic acids and proteins are directional polymers.
The directionality of a single nucleic acid is 5 to 3 whereas that of a protein is N-terminus to C-
terminus. The repeat units in nucleic acid polymers are four different nucleoside
monophosphates. The repeat units in proteins are 20 amino acids. The information content of a
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Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
15
nucleic acid, especially dsDNA, is its linear sequence. The same is true for proteins; however,
proteins typically fold into unique three-dimensional structures, which show biological activity.

Additional Problems

1. Silicon is located below carbon in the periodic chart. It is capable of forming a wide range of
bonds similar to carbon yet life is based on carbon chemistry. Why are biomolecules made of
silicon unlikely?

2. Identify the following characters of the Greek
alphabet:, , , , , , , , , , , , , , , , , , , and .

3. Give a common example of each of the weak forces at work.

4. On a hot dry day, leafy plants may begin to wilt. Why?

Abbreviated Answers

1. Covalent silicon bonds are not quite as strong as carbon covalent bonds because the bonding
electrons of silicon are shielded from the nucleus by an additional layer of electrons. In
addition, silicon is over twice the weight of carbon. Also, silicon oxides (rocks, glass) are
extremely stable and not as reactive as carbon.

2. These Greek letters are commonly used in biochemistry but this set is not the complete
Greek alphabet. alpha (), beta (), gamma (), delta (), capital delta (), epsilon (), zeta (), theta
(), kappa (), lambda (), mu (), nu (), pi (), rho (), sigma (), capital sigma (), tau (), chi (),
phi (), psi (), and omega (), the last letter of the Greek alphabet.

3. Ice is an example of a structure held together by hydrogen bonds. Sodium and chloride ions
are joined by ionic bonds in table salt crystals. A stick of butter is a solid at room temperature
because of van der Waals forces. Oil and water don't mix because hydrophobic interactions
between oil molecules cause the oil to coalesce.

4. The tonoplast loses water and begins to shrink causing the plant cell membrane to exert less
pressure on the cell wall.

Summary

The chapter begins with an outline of the fundamental properties of living systems:
complexity and organization, biological structure and function, energy transduction, and self
replication. What are the underlying chemical principles responsible for these properties? The
elemental composition of biomolecules is dominated by hydrogen, carbon, nitrogen and oxygen.
These are the lightest elements capable of forming strong covalent bonds. In particular, carbon
plays a key role serving as the backbone element of all biomolecules. It can participate in as
many as four covalent bonds arranged in tetrahedral geometry and can produce a variety of
structures including linear, branched, and cyclic compounds.
The four elements are incorporated into biomolecules from precursor compounds: CO2, NH4
+
,
NO3
-
and N2. These precursors are used to construct more complex compounds such as amino
acids, sugars, and nucleotides, which serve as building blocks for the biopolymers; proteins,
polysaccharides, and nucleic acids, as well as fatty acids and glycerol which are the building
blocks of lipids. These complex macromolecules are organized into supramolecular complexes
such as membranes and ribosomes that are components of cells, the fundamental units of life.
Proteins, nucleic acids and polysaccharides are biopolymers with structural polarity due to a
head-to-tail arrangements of asymmetric building block molecules. In these biopolymers, the
building blocks are held together by covalent bonds, but they assume an elaborate architecture
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Chemi stry Is the Logi c of Bi ol ogi cal Phenomena
16
due to weak, noncovalent forces such as van der Waals interactions, hydrogen bonds, ionic
bonds and hydrophobic interactions. The three-dimensional shape is important for biological
function, especially for proteins. At extreme conditions such as high temperature, high
pressure, high salt concentrations, extremes of pH, and so on, the weak forces may be
disrupted, resulting in loss of both shape and function in a process known as denaturation.
Thus, life is confined to a narrow range of conditions.
Life demands a flow of energy during which energy transductions occur in the organized,
orderly, small, manageable steps of metabolism, each step catalyzed by enzymes.
The fundamental unit of life is the cell. There are two types: eukaryotic cells with a nucleus
and prokaryotic cells without a nucleus. Prokaryotes are divided into two groups, eubacteria
and archaea. All cells contain ribosomes, which are responsible for protein synthesis; however,
prokaryotic cells contain little else in the way of subcellular structures. Eukaryotic cells, found
in plants, animals, fungi, and single cell organisms (protista), contain an array of membrane-
bound compartments or organelles, including a nucleus, mitochondria, chloroplasts,
endoplasmic reticulum, Golgi apparatus, vacuoles, lysosomes, and perixosomes. Organelles are
internal compartments in which particular metabolic processes are carried out.