Section 2
Biochemical Building Blocks
Chapter 17
Nucleic Acids
Section 17.1: DNA
Figure 17.2 Two Models of
DNA Structure
Scientists have studied how organisms organize and
process genetic information, revealing the following
principles:
1. DNA directs the function of living cells and is
transmitted to offspring
DNA is composed of two polydeoxynucleotide strands
forming a double helix
Section 17.1: DNA
Figure 17.2 Two Models of
DNA Structure
A gene is a DNA sequence that contains the base
sequence information to code for a gene product,
protein, or RNA
The complete DNA base sequence of an organism is its
genome
DNA synthesis, referred to as replication, involves
complementary base pairing between the parental and
newly synthesized strand
Section 17.1: DNA
2. The synthesis of RNA
begins the process of decoding
genetic information
Figure 17.3a An Overview of
Genetic Information Flow
RNA synthesis is called
transcription and involves
complementary base pairing
of ribonucleotides to DNA
bases
Each new RNA is a
transcript
The total RNA transcripts
for an organism comprise its
transcriptome
Section 17.1: DNA
3. Several RNA molecules
participate directly in the
synthesis of protein, or
translation
Figure 17.3b An Overview of
Genetic Information Flow
Messenger RNA (mRNA)
specifies the primary
protein sequence
Transfer RNA (tRNA)
delivers the specific amino
acid
Ribosomal RNA (rRNA)
molecules are components
of ribosomes
Section 17.1: DNA
The proteome is the entire
set of proteins synthesized
4. Gene expression is the
process by which cells
control the timing of gene
product synthesis in
response to environmental
or developmental cues
Figure 17.3b An Overview of
Genetic Information Flow
Metabolome refers to the
sum total of low molecular
weight metabolites
produced by the cell
Section 17.1: DNA
The Central dogma schematically summarizes the
previous information
Includes replication, transcription, and
translation
The central dogma is generally how the flow of
information works in all organisms, except some
viruses have RNA genomes and use reverse
transcriptase to make DNA (e.g., HIV)
DNA
RNA
Protein
Section 17.1: DNA
DNA consists of two
polydeoxynucleotide strands
that wind around each other to
form a right-handed double
helix
Each DNA nucleotide
monomer is composed of a
nitrogenous base, a deoxyribose
sugar, and phosphate
Figure 17.4 DNA Strand Structure
Section 17.1: DNA
Nucleotides are linked by 3′,5′phosphodiester bonds
These join the 3′-hydroxyl of
one nucleotide to the 5′phosphate of another
Figure 17.4 DNA Strand Structure
Section 17.1: DNA
Figure 17.5 DNA Structure
The antiparallel nature of the two strands allows
hydrogen bonds to form between the nitrogenous bases
Two types of base pair (bp) in DNA: (1) adenine
(purine) pairs with thymine (pyrimidine) and (2) the
purine guanine pairs with the pyrimidine cytosine
Section 17.1: DNA
Figure 17.6 DNA Structure:
GC Base Pair Dimensions
The dimensions of
crystalline B-DNA have
been precisely measured:
1. One turn of the double
helix spans 3.32 nm and
consists of 10.3 base pairs
Section 17.1: DNA
Figure 17.6 DNA Structure:
AT Base Pair Dimensions
2. Diameter of the double
helix is 2.37 nm, only
suitable for base pairing a
purine with a pyrimidine
3. The distance between
adjacent base pairs is
0.29-0.30 nm
Section 17.1: DNA
DNA is a relatively stable molecule with several noncovalent
interactions adding to its stability
1. Hydrophobic interactions—internal base clustering
2. Hydrogen bonds—formation of preferred bonds: three
between CG base pairs and two between AT base pairs
3. Base stacking—bases are nearly planar and stacked,
allowing for weak van der Waals forces between the rings
4. Hydration—water interacts with the structure of DNA
to stabilize structure
5. Electrostatic interactions—destabilization by
negatively charged phosphates of sugar-phosphate
backbone are minimized by the shielding effect of water
on Mg2+
Section 17.1: DNA
Mutation types—The most common are small single
base changes, also called point mutations
This results in transition or transversion
mutations
Transition mutations, caused by deamination, lead to
purine for purine or pyrimidine for pyrimidine
substitutions
Transversion mutations, caused by alkylating agents
or ionizing radiation, occur when a purine is
substituted for a pyrimidine or vice versa
Section 17.1: DNA
Point mutations that occur in a population with any
frequency are referred to as single nucleotide
polymorphisms (SNPs)
Point mutations that occur within the coding portion
of a gene can be classified according to their impact on
structure and/or function:
Silent mutations have no discernable effect
Missense mutations have an observable effect
Nonsense mutations changes a codon for an amino
acid to that of a premature stop codon
Section 17.1: DNA
Insertions and deletions, or indels, occur from one to
thousands of bases
Indels that occur within the coding region that are
not divisible by three cause a frameshift mutation
Genome rearrangements can cause disruptions in
gene structure or regulation.
Occur as a result of double strand breaks and can
lead to inversions, translocations, or duplications
Section 17.1: DNA
DNA Structure: The Genetic Material
In the early decades of the twentieth century, life
scientists believed that of the two chromosome
components (DNA and protein) that protein was most
likely responsible for transmission of inherited traits
The work of several scientists would lead to another
conclusion
Section 17.1: DNA
DNA Structure: Variations on a
Theme
Figure 17.12 A-DNA, B-DNA,
and Z-DNA
Watson and Crick’s discovery is
referred to as B-DNA (sodium
salt)
Another form is the A-DNA,
which forms when RNA/DNA
duplexes form
Z-DNA (zigzag conformation) is
left-handed DNA that can form
as a result of torsion during
transcription
Section 17.1: DNA
DNA can form other structures, including
cruciforms, which are cross-like structures, probably
a result of palindromes (inverted repeats)
Packaging large DNA molecules to fit inside a cell or
nucleus requires a process termed supercoiling
Section 17.1: DNA
DNA Supercoiling
Facilitates several
biological processes:
packaging of DNA,
replication, and
transcription
Linear and circular DNA
can be in a relaxed or
supercoiled shape
Figure 17.13 Linear and Circular DNA
and DNA Winding
Section 17.1: DNA
Chromosomes and Chromatin
Figure 17.17 The E. coli
Chromosome Removed
from a Cell
DNA is packaged into
chromosomes
Prokaryotic and eukaryotic
chromosomes differ significantly
Prokaryotes—the E. coli
chromosome is a circular DNA
molecule that is extensively
looped and coiled
Supercoiled DNA complexed
with a protein core
Section 17.1: DNA
Eukaryotes have extraordinarily
large genomes when compared to
prokaryotes
Figure 17.18 Electron
Micrograph of Chromatin
Chromosome number and length
can vary by species
Each eukaryotic chromosome
consists of a single, linear DNA
molecule complexed with histone
proteins to form nucleohistone
Chromatin is the term used to
describe this complex
Section 17.1: DNA
Figure 17.18 Electron
Micrograph of Chromatin
Nucleosomes are formed by the
binding of DNA and histone proteins
Nucleosomes have a beaded
appearance when viewed by
electron micrograph
Histone proteins have five major
classes: H1, H2A, H2B, H3, and H4
A nucleosome is positively coiled
DNA wrapped around a histone core
(two copies each of H2A, H2B, H3,
and H4)
Section 17.1: DNA
Prokaryotic Genomes—Investigation of E. coli has
revealed the following prokaryotic features:
1. Genome size—usually considerably less DNA and
fewer genes (E. coli 4.6 megabases) than eukaryotic
genomes
2. Coding capacity—compact and continuous genes
3. Gene expression—genes organized into operons
Prokaryotes often contain plasmids, which are usually
small and circular DNA with additional genes (e.g.,
antibiotic resistance)
Section 17.1: DNA
Eukaryotic Genomes—Investigation has revealed the
organization to be very complex
The following are unique eukaryotic genome features:
1. Genome size—eukaryotic genome size does not
necessarily indicate complexity
2. Coding capacity—enormous protein coding capacity,
but the majority of DNA sequences do not have coding
functions
3. Coding continuity—genes are interrupted by
noncoding introns, which can be removed by splicing
from the primary RNA transcript
Section 17.1: DNA
Existence of introns and exons allows eukaryotes to
produce more than one polypeptide from each proteincoding gene
Alternative splicing allows for various combinations of
exons to be joined to form different mRNAs
Intergenic sequences are those sequences that do not
code for polypeptide primary sequence or RNAs
Section 17.1: DNA
Of the 3,200 Mb of the human genome, only 38%
comprise genes and related sequence
Only 4% codes for gene products
Humans have about 23,000 protein coding
genesand several ncRNA genes
Section 17.1: DNA
Figure 17.24 Human
Protein-Coding Genes
25% of known proteincoding genes are related to
DNA synthesis and repair
21% signal transduction
17% general biochemical
functions
38% other activities
Over 60% of the human
genome is intergenic sequences
Section 17.1: DNA
Two classes: tandem repeats and interspersed genomewide repeats
Tandem repeats (satellite DNA) are DNA sequences
in which multiple copies are arranged next to each
other
Certain tandem repeats play structural roles
like centromeres and telomeres
Some are small, like microsatellites (1-4 bp) and
minisatellites (10-100 bp)
Used as markers in genetic disease, forensic
investigations, and kinship
Section 17.1: DNA
Interspersed genome-wide repeats are repetitive
sequences scattered around the genome
Often involve mobile genetic elements that can
duplicate and move around the genome
Transposons and retrotransposones
LINEs (long interspersed nuclear elements) and
SINEs (short interspersed nuclear elements) are
two types of transposons
Section 17.2: RNA
RNA is a versatile molecule, not
only involved in protein
synthesis, but plays structural
and enzymatic roles as well
Differences between DNA and
RNA primary structure:
Figure 17.25 Secondary
Structure of RNA
1. Ribose sugar instead of
deoxyribose
2. Uracil nucleotide instead of
thymine
Section 17.2: RNA
3. RNA exists as a single strand
that can form complex threedimensional structures by base
pairing with itself
4. Some RNA molecules have
catalytic properties, or ribozymes
(e.g., self-cleavages or cleave other
RNA)
Figure 17.25 Secondary
Structure of RNA
Section 17.2: RNA
Transfer RNA
Transfer RNA (tRNA) molecules
transport amino acids to ribosomes
for assembly (15% of cellular RNA)
Average length: 75 bases
Figure 17.26a Transfer RNA
At least one tRNA for each amino
acid
Structurally look like a warped
cloverleaf due to extensive
intrachain base pairing
Section 17.2: RNA
Amino acids are attached via
specific aminoacyl-tRNA
synthetases to the end
opposite the three nucleotide
anticodon
Figure 17.26b Transfer RNA
Anticodon allows the tRNA
to recognize the correct
mRNA codon and properly
align its amino acid for
protein synthesis
The tRNA loops help
facilitate interactions with
the correct aminoacyl-tRNA
synthetases
Section 17.2: RNA
Ribosomal RNA
Ribosomal RNA (rRNA) is the most abundant RNA
in living cells with a complex secondary structure
Components of ribosomes (eukaryotes and
prokaryotes)
Similar in shape and function, both have a small and
large subunit, but differ in size and chemical
composition
Eukaryotic are larger (80S) with a 60S and 40S
subunit, while prokaryotic are smaller (70S) with 50S
and 30S subunits
Section 17.2: RNA
Figure 17.27 rRNA Structure
rRNA plays a role in scaffolding as well as enzymatic
functions
Ribosomes also have proteins that interact with rRNA
for structure and function
Section 17.2: RNA
Messenger RNA
Messenger RNA (mRNA) is the carrier of genetic
information from DNA to protein synthesis
(approximately 5% of total RNA)
mRNA varies considerably in size
Prokaryotic and eukaryotic mRNA differ in several
respects
Prokaryotes are polycistronic while eukaryotes are
usually monocistronic
mRNAs are processed differently; eukaryotic mRNA
requires 5′ capping, 3′ tailing, and splicing
Section 17.2: RNA
Noncoding RNA
RNAs that do not directly code for polypeptides are
called noncoding RNAs (ncRNAs)
Micro RNAs and small interfering RNAs are among
the shortest and involved in the RNA-induced
silencing complex
Small Nucleolar RNAs (snoRNAs) facilitate chemical
modifications to rRNA in the nucleolus
Section 17.2: RNA
Noncoding RNA
Small interfering RNAs (siRNAs) are 21-23 nt
dsRNAs that play a crucial role in RNA interference
(RNAi)
Small nuclear RNAs (snRNAs) combine with proteins
to form small nuclear ribonucleoproteins (snRNPs)
and are involved in splicing
Section 17.3: Viruses
Viruses lack the properties that distinguish life
from nonlife (e.g., no metabolism)
Once a virus has infected a cell, its nucleic acid can
hijack the host’s nucleic acid and proteinsynthesizing machinery
The virus can then make copies of itself until it
ruptures the host cell or integrates into the host cell’s
chromosome
Section 17.3: Viruses
A viral infection can provide biochemical insight,
because it subverts the host cell’s function
Viruses can cause numerous different diseases, but
have also been invaluable in the development of
recombinant DNA technology
Human papillomavirus can cause cervical cancer
Chapter 18
Genetic Information
Chapter 18: Overview
Numerous contacts are involved
including hydrophobic
interactions, hydrogen bonding,
and ionic bonds
Between amino acid residues
and edges of bases within the
major and minor grooves
Figure 18.1 Examples of
Specific Amino AcidNucleotide Base
Interactions during ProteinDNA Binding
Chapter 18: Overview
Figure 18.2 DNAProtein Interactions
Three-dimensional structures of DNA-binding
proteins have surprisingly similar structures
Most possess a twofold axis of symmetry and can be
separated into families:
1. Helix-turn-helix
2. Helix-loop-helix
3. Leucine zipper
4. Zinc finger
Chapter 18: Overview
Figure 18.2 DNAProtein Interactions
For example, many leucine zipper transcription
factors form dimers as their leucine-containing ahelices associate via van der Waals forces
Section 18.1: Genetic Information: Replication, Repair, and Recombination
All viable living organisms possess rapid and
accurate DNA synthesis and effective DNA repair
mechanisms
Variation may also be important for adaptability to
environments
Variation is caused by genetic recombination and
mutation
Section 18.1: Genetic Information: Replication, Repair, and Recombination
DNA Replication
DNA replication occurs before
cell division; the mechanism is
similar in all living organisms
After the two strands have
separated, each serves as a
template for synthesis of a
complementary strand
This process is referred to as
semiconservative replication
Figure 18.3 Semiconservative
DNA Replication
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.4 The Meselson-Stahl Experiment
This was first demonstrated in 1958 in an
experiment by Matthew Meselson and Franklin Stahl
The experiment involved generating DNA with a
greater density by incorporating the heavy nitrogen
isoptope 15N
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Most DNA replication takes place at replication
factories, which are relatively stationary during the
process
DNA Synthesis in Prokaryotes—DNA replication in
E. coli consists of several basic steps:
DNA unwinding requires helicases, which are ATPdependent enzymes that catalyze the unwinding of
duplex DNA (e.g., DnaB in E. coli)
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.5 The DNA
Polymerase Reaction
Primer synthesis is the formation of short RNA
segments (primers) required for the initiation of DNA
replication by primase (e.g., dnaG)
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.5 The DNA
Polymerase Reaction
DNA synthesis is the synthesis of complementary
DNA in a 5′3′ direction catalyzed by a large
multienzyme complex referred to as DNA polymerase
Section 18.1: Genetic Information: Replication, Repair, and Recombination
DNA polymerase III (pol
III) is the major DNA
polymerase in prokaryotes
Catalyzes the nucleophilic
attack of the 3′-hydroxyl
group onto the a-phosphate
Figure 18.6 Mechanism of
DNA Polymerases
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Pol III holoenzyme is composed of at least 10 subunits
The core polymerase is formed of three subunits: a, e,
and 
The b-protein (sliding clamp) is two subunits and
forms a donut-shaped ring around the template DNA
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.7 Cross Section
of the b2-Clamp of DNA
Polymerase III
The g complex is composed of g, d, d, c, and 
Acts as the clamp-loader, loading b2-clamp dimer
b2-Clamp promotes processivity (prevents dissociation
of polymerase from the DNA template)
The g-complex is ejected in an ATP-dependent
process and replication can proceed
Section 18.1: Genetic Information: Replication, Repair, and Recombination
The DNA replicating machine (replisome) consists of
two pol III holoenzymes, the primosome, and DNA
unwinding proteins
There are four other DNA polymerases:
DNA polymerase I is involved in RNA primer
removal and replacement with DNA
DNA polymerase II, IV, and V are involved in DNA
repair translesion repair enzymes
All three are part of the SOS response that
prevent cell death due to high levels of DNA
damage
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Joining DNA fragments—frequently during DNA
synthesis, DNA segments must be joined together
DNA ligase catalyzes the formation of the
phosphodiester bond between adjoining nucleotides
Supercoiling control is accomplished by DNA
topoisomerases
Relieve torque in the DNA, so the replication
process is not slowed
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Type I topoisomerases produce
transient single-strand breaks
Type II topoisomerases produce
transient double-strand breaks
DNA gyrase—a type II
topoisomerase in prokaryotes
helps separate the replication
products and create the negative
(-) supercoils required for
genome packaging
Figure 18.8 Replication
of Prokaryotic DNA
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.9 DnaA Structure
In E. coli when the ATP/ADP
ratio is high and there is
enough DnaA, replication can
begin at the initiation site
(oriC)
Replication proceeds in both
directions with each
replication fork having
helicases and a replisome
E. coli only has one origin of
replication, making it a single
replication unit (replicon)
organism
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.10 DNA Replication
at a Replication Fork
DNA synthesis only occurs in the 5′3′ direction, so
one strand is continuously synthesized (leading
strand) while the other is not (lagging strand)
The lagging strand is synthesized in short 5′3′
segments called Okazaki fragments (1,000–2,000
nucleotides)
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Replication begins when DnaA proteins bind to
five to eight 9-bp sites within the oriC
The oligomerization of DnaA results in a
nucleosome-like structure requiring ATP and
histone-like protein (HU)
Causes three 13-bp repeats near the DnaA-DNA
complex to open
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.11 Replication
Fork Formation
DnaB complexed with DnaC enters the open oriC
region; once DnaB is loaded, DnaC is released
The replication fork moves forward as DnaB
unwinds the helix
Topoisomerases relieve torque ahead of the replisome
Single strands are kept apart by numerous copies of
single-stranded DNA-binding protein (SSB)
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.12 E. coli DNA
Replication Model
For pol III to initiate DNA synthesis an RNA primer
must be present
On the leading strand, only a single primer is required
On the lagging strand, a primer is required for each
Okazaki fragment
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.12 E. coli DNA
Replication Model
Pol III synthesizes at the 3′ end of the primer
RNA primers are removed by pol I, which then
synthesizes complementary DNA
DNA ligase then joins Okazaki fragments
Tandem operation of two pol III complexes requires
the lagging strand be looped around the replisome
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Despite the complexity and high processivity rate
(1,000 base pairs per second per replication fork) of
DNA replication in
E. coli, it is amazingly accurate—one error per 109 or
1010 base pairs
This is due to the precise nature of the copying
process (complementary), proofreading mechanism
of DNA pol I and III, and postreplication repair
mechanisms
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.13 Role of Tus
in DNA Replication
Termination in E. coli
Replication ends when the replication forks meet at
the other side of the circular chromosome at the
termination site (ter region)
The DNA-binding protein tus binds to the ter causing
replication arrest
Section 18.1: Genetic Information: Replication, Repair, and Recombination
DNA Synthesis in Eukaryotes has a
great deal in common with
prokaryotes; they also have
significant differences
Figure 18.14 The Eukaryotic
Cell Cycle
DNA Polymerase There are 15
eukaryotic DNA polymerases
Three (a, d, and e) are involved
in nuclear DNA replication
Pol g replicates and repairs
mitochondrial DNA
Polymerases b, z and  function
in nuclear DNA repair
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.14 The Eukaryotic
Cell Cycle
Timing of replication—eukaryotic
replication is limited to a very
specific phase of the cell cycle (S
phase)
Replication rate is slower in
eukaryotes (50 bp per second per
replication fork) due to complex
chromatin structure
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Replicons—eukaryotes have
multiple replicons (about every 40
kb) to compress the replication of
their large genomes into short
periods
Humans have 30,000 origins
of replication
Okazaki fragments are from 100
to 200 nucleotides long
Figure 18.15 Multiple-Replicon
Model of Eukaryotic
Chromosomal DNA Replication
Section 18.1: Genetic Information: Replication, Repair, and Recombination
The Eukaryotic Replication
Process—In higher eukaryotes,
replication begins with the
assembly of the preinitiation
replication complex (preRC)
Process begins in early G1 when
cdk and cyclin levels are low,
limiting DNA replication to once
per cell cycle
preRC assembly begins when the
origin replication complex (ORC)
binds to the origin
Figure 18.16 Formation of a Preinitiation
Replication Complex
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Cdc6 and Cdt1 bind ORC and
recruit the MCM complex (helicase)
Conversion of the preRC to an
active initiation complex requires
the addition of pol a/primase, pol e,
and accessory proteins
Cell cycle regulating kinases then
phosphorylate and activate preRC
components
The proteins that bind ORC and
complete preRC structure are the
replication licensing factors (RLFs)
Figure 18.17 Eukaryotic
Replication Fork Formation
Section 18.1: Genetic Information: Replication, Repair, and Recombination
When the initiation complex is
active, newly phosphorylated MCM
separates the DNA strands
Each strand is then stabilized
by replication protein A (RPA)
Pol a/Primase extends each primer
by a short segment of DNA, then
polymerase d and e continue the
process
Replication factor C (RFC), a clamp
loader, controls the attachment of
polymerase d
Figure 18.17 Eukaryotic
Replication Fork Formation
Section 18.1: Genetic Information: Replication, Repair, and Recombination
After binding ATP, RFC binds PCNA,
a processivity factor
RFC/PCNA complex converts DNA
polymerase d and e into processive
enzymes
RFC/PCNA complex loads either
polymerase, triggering ATP
hydrolysis
Figure 18.18 Replication
Protein A Structure
Replication occurs until replicons
meet and fuse
Section 18.1: Genetic Information: Replication, Repair, and Recombination
When the replication machinery reaches the 3′ end of
the lagging strand, there is insufficient space for a new
RNA primer
This leaves the end of the chromosome without its
complementary base pairs
Chromosomes with 3′-ssDNA overhangs are very
susceptible to nuclease digestion
Eukaryotes compensate with telomerase, a
ribonucleoprotein with reverse transcriptase ability
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.19 TelomeraseCatalyzed Extension of a
Chromosome
Telomerase has an RNA base
sequence complementary to the TGrich sequence of telomeres
Telomerase uses this sequence
to synthesize a single-stranded
DNA to extend the 3′ strand of
the telomere
Afterward the normal
replication machinery
synthesizes a primer and
Okazaki fragment
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.19 TelomeraseCatalyzed Extension of a
Chromosome
The chromosome ends are then
sequestered and stabilized by
telomere end-binding proteins
(TEBPs) and telomere repeatbinding factors (TRFs)
TEBPs bind GT-rich
telomere sequences
TRFs secure the 3′ overhang
Telomerase is normally only
active in germ cells
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.19 TelomeraseCatalyzed Extension of a
Chromosome
During normal human aging,
the telomeres of somatic cells
shorten over time
Once telomeres are reduced
to a critical length,
chromosome replication
cannot occur
Telomere shortening causes
cell death
90% of all cancers have
hyperactive telomerase
Section 18.1: Genetic Information: Replication, Repair, and Recombination
DNA Repair
Mutations are caused by metabolic activities or
environmental exposures on DNA
The natural rate of mutation is about 1.0 mutation
per 100,000 genes per generation
Cells possess a great variety of DNA repair
mechanisms
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Direct Repairs
A few types of DNA damage
can be repaired without the
removal of nucleotides
Figure 18.20 Photoreactivation
Repair of Thymine Dimers
Breaks in the phosphodiester
linkages can be repaired by
DNA ligase
In photoreactivation repair,
pyrimidine dimers are
restored to their original
monomeric structure using a
photoreactivating enzyme and
visible light
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.21 Base
Excision Repair
The resulting apurinic or apyrimidinic sites are
resolved through the action of nucleases that remove
the residue, DNA polymerase (pol I in bacteria; DNA
polymerase b in mammals), and DNA ligase
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.21 Base
Excision Repair
Single Strand Repairs use the complementary,
undamaged strand as a template
Base excision repair is a mechanism that removes
and then replaces individual nucleotides whose bases
have undergone damage
A DNA glycosylase cleaves the N-glycosidic linkage
between the damaged base and the deoxyribose
Section 18.1: Genetic Information: Replication, Repair, and Recombination
In nucleotide excision repair, bulky (230 nt) lesions are removed and the
resulting gap is filled
Two types: global genomic repair and
transcription coupled repair
The excision enzymes of this process
seem to recognize the distortion rather
than the base sequence
Figure 18.22 Excision Repair of
a Thymine Dimer in E. coli
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Transcription coupled repair occurs only on a strand
being actively transcribed
Damage is recognized when RNA polymerase is
stalled
Mfd is a transcription-repair coupling factor that
displaces the polymerase and recruits UvrA2B to
initiate damage removal
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Mismatch repair is a single-strand repair mechanism
that corrects helix distorting base mispairings resulting
from proofreading errors or replication slippage
A key feature is the capacity to distinguish between
old and newly synthesized strands
For a finite amount of time each daughter strand is
hemimethylated, i.e., it consists of one methylated and
one nonmethylated strand
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Double-strand breaks (DSBs) are especially dangerous
for cells because they can result in a lethal breakdown of
chromosomes
Caused by radiation, ROS, DNA damaging agents, or
as result of replication errors
DSBs are repaired by two mechanisms: nonhomologous end joining (NHEJ) and homologous
recombination
NHEJ is error prone because there is no
requirement for sequence homology
Recombination will be explained next
Section 18.1: Genetic Information: Replication, Repair, and Recombination
DNA Recombination
Recombination is the rearrangement of DNA
sequences by exchanging segments from different
molecules
Genetic recombination is a principle source of the
variations that make evolution possible
Two types of recombination:
General recombination occurs between homologous
DNA molecules (most common during meiosis)
Site-specific recombination—the exchange of
sequences only requires short regions of DNA
homology (e.g., transposition)
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Bacterial Recombination is involved in several forms
of intermicrobial DNA transfer:
1. Transformation is the process of naked DNA
molecules entering the cell through small holes in the
cell wall
2. Transduction is when a bacteriophage inadvertently
carries bacterial DNA to a recipient cell
3. Conjugation is an unconventional sexual mating that
involves passing DNA from a donor cell through a sex
pilus to a recipient cell
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Eukaryotic Recombination occurs during the first
phase of meiosis to ensure accurate homologous
chromosome pairing and crossing over
It is similar to prokaryotic recombination but has a
larger number of proteins because of the more complex
genomes
Rad52 is believed to be the initial sensor of DSBs
Rad51, BRCA1, and BRCA2 are involved in DSB
repair
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Site Specific Recombination and
Transposition—This process relies
on short segments of homologous
DNA called attachment (att) sites or
insertional (IS) elements
Recombination at these sites can
lead to insertions, deletions,
inversions, and translocations
Integration of bacteriophage l DNA
into the E. coli chromosome requires
homologous att sites in the phage
and bacterial genomes
Figure 18.27 Insertion of the Bacteriophage l
Genome into the E. coli Chromosome
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Barbara McClintock, a geneticist working with
Indian Corn (maize), found that mobile genetic
elements were responsible for variation in corn kernel
color (1940s)
In 1967, transposable elements were confirmed and
Dr. McClintock received the Nobel Prize in physiology
and medicine
Section 18.1: Genetic Information: Replication, Repair, and Recombination
The IS elements of simple prokaryotic transposons
consist of a transposase gene flanked by short inverted
terminal repeats
More complex bacterial transposons (composite
transposons) will have specific genes (e.g., antibiotic
resistance) between simple IS elements
Insertion of the Tn3 transposon into bacterial DNA
involves the duplication of the target site
Two mechanisms of transposition have been
observed: replicative and nonreplicative
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Figure 18.28 Bacterial Insertion Elements
Section 18.1: Genetic Information: Replication, Repair, and Recombination
Replicative
transposition involves
the transfer of one
strand of the donor DNA
to the target position,
followed by replication
and site-specific
recombination
Figure 18.29a Replicative
Transposition
Section 18.2: Transcription
Figure 18.31 DNA
Coding Strand
Transcription is a complex process involving a variety
of enzymes and associated proteins
RNA polymerase is the enzyme that catalyzes the
addition of ribonucleotides in a 5′3′ direction
The template strand (-) of DNA is antiparallel to
the new RNA strand
The noncoding strand (+) has the same base sequence
as the RNA, except the transcript has uracil for
thymine
Section 18.2: Transcription
Figure 18.33 Transcription
Initiation in E. coli
Transcription consists of three stages: initiation,
elongation, and termination
Initiation involves the binding of RNA polymerase to
the promoter (regulatory sequence upstream of a gene)
Section 18.2: Transcription
Two short consensus
sequences at -10 (Pribnow box)
and -35 are similar among
many bacterial species
Figure 18.34 Typical E. coli
Transcription Unit
Section 18.2: Transcription
Figure 18.36 Intrinsic
Termination
Two types of transcription termination in bacteria:
intrinsic termination and rho-dependent termination
In intrinsic termination, RNA synthesis is terminated
by the transcription of an inverted repeat sequence
The inverted repeat forms a stable hairpin that
causes the RNA polymerase to slow or stop
RNA transcript is released due to weak base-pair
interactions
Section 18.2: Transcription
In rho-dependent termination,
RNA synthesis is terminated with
the aid of the ATP-dependent
helicase rho factor
Rho binds to a specific
recognition sequence on the
nascent RNA chain, upstream
from the termination site
Unwinds the RNA-DNA helix
to release the transcript
Figure 18.37 Rho-Dependent
Termination
Section 18.2: Transcription
Transcription in Eukaryotes
Similar to prokaryotic transcription in several
aspects
Polymerases are similar in structure and function
Initiation factors are distantly related, but perform
similar functions
Regulatory mechanisms differ significantly in both
organisms
One major difference is the limited access to DNA of
the transcription machinery
Section 18.2: Transcription
Figure 18.39 Chromatin
Remodeling
Chromatin is usually at least
partially condensed
For transcription to occur, DNA
most be sufficiently accessible for
RNA polymerase
Histone tails of nucleosomes are
modified by histone acetyl
transferases (HATs) to allow
access
Histone-DNA contacts are
weakened by chromatin
remodeling complexes, SWI,SNF,
and NURF
Section 18.2: Transcription
Eukaryotic promoters- Promoter sequences in
eukaryotic DNA are larger, more complex, and
variable than in prokaryotes
Each consists of a core promoter which can be
focused or dispersed
Focused contain the transcription start site (TSS)
and core promoter elements (CPE)
The most studied CPE is the consensus sequence
called the TATA box (25–30 bp upstream)
Section 18.2: Transcription
TATA-binding protein (TBP) a subunit of the
transcription factor TFIID binds the TATA box and is
the first step of RNA polymerase assembly
Other core elements include the Inr (initiator), BRE
(B recognition element), and DPE (downstream
promoter element)
Dispersed genes often have multiple TSSs which are
distributed over a broad region of 50-100 basepairs
Typically occur within CpG islands and commonly
found in vertebrates.
CpGs are now believed to facilitate nucleosome
destabilization
Section 18.2: Transcription
Figure 18.40 The Eukaryotic RNAPII Core
Promoter
Proximal promoter elements are transcription factor
binding sites within 250 bp of the TSS
The frequency of transcription initiation is often
affected by upstream sites such as the CAAT box and
GC box
Can also be affected by enhancers that may be
thousands of base pairs upstream
Section 18.2: Transcription
Figure 18.46 The Methylated
Cap of Eukaryotic mRNA
RNA Processing- mRNA is the product of extensive
posttranscriptional processing
Pre-mRNAs become associated with about 20 different
types of nuclear proteins in ribonucleoprotein particles
(hnRNP)
Shortly after transcription begins, capping occurs at
the 5′ end
Section 18.2: Transcription
Figure 18.46 The Methylated
Cap of Eukaryotic mRNA
The cap structure consists of a 7-methylguanosine
linked to the mRNA through a triphosphate linkage
Synthesized when the transcript is about 30 nt long
The 5′ cap serves to protect the 5′ end from
exonucleases and promotes translation
Section 18.2: Transcription
One of the more remarkable features of eukaryotic
RNA processing is the removal of introns from an RNA
transcript (RNA splicing)
Introns are cut out of the primary transcript and exons
are linked together to form a functional product
The number of introns and exons is highly variable
among different genes and species
RNA splicing takes place in a 4.8-megadalton RNAprotein complex called the spliceosome
Splicing occurs at certain conserved sequences
Section 18.2: Transcription
Figure 18.47 RNA Splicing
In eukaryotic nuclear pre-mRNA transcripts, there are
two intron types: GU-AG and AU-AC
In GU-AG introns, 5′-GU-3′ and 5′-AG-3′ are the first
and last dinucleotides of the intron, respectively
The splice event occurs in two reactions:
1. A 2′-OH of an adenosine nucleotide within the
intron attacks a phosphate in the 5′ splice site,
forming a lariat
Section 18.2: Transcription
2. The lariat is cleaved and
the two exons joined when
the 3′-OH of the upstream
exon attacks a phosphate
adjacent to the lariat
5′ splice site is the donor
site and the 3′ splice site
is the acceptor site
Four active spliceosomes
form with each pre-mRNA
to form a supraspliceosome
Figure 18.47 RNA Splicing
Section 18.2: Transcription
An exon junction complex (EJC) binds to each splice
site 20 nt unpstream of the exon-exon junction
EJCs play a role in nonsense-mediated decay
protecting against premature stop codons
Result from splicing errors, random mutations or
rearrangements
Four active spliceosomes form with the majority of
mammalian pre-mRNAs to form a supraspliceosome
Section 18.3: Gene Expression
The precise and timely regulation of gene
expression is required for handling changing
environments, cell differentiation, and intercellular
cooperation
Constitutive genes are routinely transcribed
because they code for gene products required for
normal cell function
Other genes are inducible or repressible, depending
on the cellular state
Section 18.3: Gene Expression
Figure 18.49 The lac
Operon in E. coli
Gene Expression in Prokaryotes
The highly regulated metabolism of prokaryotes such
as E. coli allows these organisms to manage limited
resources and to respond to a changing environment
Control of inducible genes is often affected by the
groups of linked structural and regulatory genes called
operons
Section 18.3: Gene Expression
Riboswitches are metabolite-sensing domains in the
5-untranslated regions of mRNAs (mostly bacteria)
Riboswitches monitor cellular metabolite
concentrations
Genes containing riboswitches typically code for
proteins that are involved in the synthesis of molecules
that are expensive to produce, such as TPP (thiamine
pyrophosphate) or FMN (flavin mononucleotide)
Composed of two structural elements: an aptamer
(binds metabolite) and expression platform (expression
regulator)
Section 18.3: Gene Expression
Figure 18.51a Riboswitches
When the aptamer binds the metabolite, it undergoes a
structural change that alters the structure of the
expression platform
For example, when TPP binds its aptamer, the
riboswitch is converted from a structure that has an
open translation initiation site to one with the start site
sequestered in a hairpin loop, blocking translation
Section 18.3: Gene Expression
Gene Expression in Eukaryotes
Eukaryotic genomes have more intricate regulation
of gene expression
Gene expression is regulated at the following levels:
genomic control, transcriptional control, RNA
processing, RNA editing, RNA transport, and
translational control
Section 18.3: Gene Expression
Figure 18.52 Eukaryotic
Gene Regulatory Proteins
Genomic Control—Two major influences on
transcription initiation: chromatin structure and
transcription factor-regulated RNA polymerase
complex formation
A significant amount of regulation occurs through
transcription initiation control
The particular set of proteins that assembles on a
regulatory DNA sequence is a result of the DNA
structure, gene regulatory proteins present, and their
affinity for one another
Section 18.3: Gene Expression
RNA processing—Among the
most important types of RNA
processing is alternative splicing
The joining of different
combinations of exons to form
cell-specific proteins
Figure 18.53 RNA Processing
Section 18.3: Gene Expression
In general, mRNAs with longer poly(A) tails are more
stable, increasing their opportunities for translation
The site of polyadenylation can alter an mRNA’s
structural and functional properties
There are two forms of IgM: membrane bound and
secreted
The plasma membrane bound form produced
during early B-lymphocyte differentiation has two
extra exons because the polyadenylation sequence
is further downstream
Section 18.3: Gene Expression
After transcription, base changes are effected by means
of RNA editing
Alterations in mRNA base sequence can have
several consequences: RNA stability, translation
initiation, alteration of splice sites, and amino acid
sequence changes
Posttranscriptional Gene Silencing—A form of
postranscriptional gene regulation involves microRNAs
(miRNAs)
miRNAs inhibit translation by binding to
complementary sequences in the 3′-UTR of target
mRNAs
Section 18.3: Gene Expression
Translational Control—Covalent modification of
several translation factors has been shown to alter
translation rate in response to various stimuli
For example, when cellular iron is low, a repressor
protein binds mRNAs coding for the iron storage
protein ferritin
Signal Transduction and Gene Expression—Cells can
alter gene expression patterns in response to signals
from their environment
This is often initiated by binding of a ligand to a
receptor that then initiates a signal transduction
cascade
Section 18.3: Gene Expression
The best understood signal transduction examples are
for cell proliferation, because of the tremendous amount
of research done to understand cancer
This includes two complicating features of intracellular
signal molecules:
Each type of signal may activate one or more
pathways
Signal transduction pathways may result in the
same or overlapping responses
Section 18.3: Gene Expression
Growth factor effects are believed to include gene
expression, which specifically overcomes inhibitions at cellcycle checkpoints—especially the G1 checkpoint
Induce two classes of genes at the end of their signal
transduction cascades
Early response genes are rapidly activated (within 15
minutes) and are often transcription factors
Includes the protooncogenes jun, fos, and myc
Section 18.3: Gene Expression
Delayed response genes
are induced by the
activities of the
transcription factors and
proteins produced during
the early response phase
Can include Cdks and
cyclins
Figure 18.56 Eukaryotic Gene Expression
Triggered by Growth Factor Binding
Chapter 7
Carbohydrates
Chapter 7: Overview
Carbohydrates are the most abundant biomolecule
in nature
Have a wide variety of cellular functions: energy,
structure, communication, and precursors for other
biomolecules
They are a direct link between solar energy and
chemical bond energy
Section 7.1: Monosaccharides
Figure 7.1 General Formulas
for the Aldose and Ketose
Forms of Monosaccharides
Monosaccharides, or simple sugars, are polyhydroxy
aldehydes or ketones
Sugars with an aldehyde functional group are
aldoses
Sugars with an ketone functional group are ketoses
Section 7.1: Monosaccharides
Monosaccharide Stereoisomers
An increase in the number of
chiral carbons increases the
number of possible optical
isomers
2n where n is the number of chiral
carbons
Almost all naturally occurring
monosaccharides are the D form
All can be considered to be
derived from D-glyceraldehyde
or nonchiral dihydroxyacetone
Figure 7.3 The D Family of Aldoses
Section 7.1: Monosaccharides
Figure 7.5 Formation of
Hemiacetals and Hemiketals
Cyclic Structure of Monosaccharides
Sugars with four or more carbons exist primarily in
cyclic forms
Ring formation occurs because aldehyde and ketone
groups react reversibly with hydroxyl groups in an
aqueous solution to form hemiacetals and hemiketals
Section 7.1: Monosaccharides
Figure 7.6 Monosaccharide
Structure
The two possible diastereomers that form because of
cyclization are called anomers
Hydroxyl group on hemiacetal occurs on carbon 1 and
can be in the up position (above ring) or down position
(below ring)
In the D-sugar form, because the anomeric carbon is
chiral, two stereoisomers of the aldose can form the aanomer or b-anomer
Section 7.1: Monosaccharides
Figure 7.7 Haworth Structures
of the Anomers of D-Glucose
Haworth Structures—these structures more
accurately depict bond angle and length in ring
structures than the original Fischer structures
In the D-sugar form, when the anomer hydroxyl is up
it gives a b-anomeric form (left in Fischer projection)
while down gives the a-anomeric form (right)
Section 7.1: Monosaccharides
Figure 7.8 Furan and Pyran
Five-membered rings are called furanoses and sixmembered rings are pyranoses
Cyclic form of fructose is fructofuranose, while
glucose in the pyranose form is glucopyranose
Figure 7.9 Fischer and Haworth Representations of D-Fructose
Section 7.1: Monosaccharides
Reaction of Monosaccharides
The carbonyl and hydroxyl groups can undergo
several chemical reactions
Most important include oxidation, reduction,
isomerization, esterification, glycoside formation, and
glycosylation reactions
Section 7.1: Monosaccharides
Figure 7.17 Formation
of Acetals and Ketals
Glycoside Formation—hemiacetals and hemiketals
react with alcohols to form the corresponding acetal
and ketal
When the cyclic hemiacetal or hemiketal form of the
monosaccharide reacts with an alcohol, the new linkage
is a glycosidic linkage and the compound a glycoside
Section 7.1: Monosaccharides
Figure 7.18 Methyl Glucoside Formation
Naming of glycosides specifies the sugar component
Acetals of glucose and fructose are glucoside and
fructoside
Section 7.1: Monosaccharides
If an acetal linkage is formed between the hemiacetal
hydroxyl of one monosaccharide and the hydroxyl of
another, this forms a disaccharide
In polysaccharides, large numbers of monosaccharides
are linked together through acetal linkages
Section 7.1: Monosaccharides
Glycosylation Reactions attach sugars or glycans
(sugar polymers) to proteins or lipids
Catalyzed by glycosyl transferases, glycosidic
bonds are formed between anomeric carbons in
certain glycans and oxygen or nitrogen of other
types of molecules, resulting in N- or O-glycosidic
bonds
Section 7.1: Monosaccharides
Glycation is the reaction of reducing sugars with
nucleophilic nitrogen atoms in a nonenzymatic reaction
Most researched example of the glycation reaction is
the nonenzymatic glycation of protein (Maillard
reaction)
The Schiff base that forms rearranges to a stable
ketoamine, called the Amadori product
Can further react to form advanced glycation end
products (AGEs)
Promote inflammatory processes and involved in
age-related diseases
Section 7.1: Monosaccharides
Figure 7.20 The Maillard
Reaction
Section 7.1: Monosaccharides
Figure 7.21 a-D-glucopyranose
Important Monosaccharides
Glucose (D-Glucose) —originally called dextrose, it is
found in large quantities throughout the natural
world
The primary fuel for living cells
Preferred energy source for brain cells and cells
without mitochondria (erythrocytes)
Section 7.1: Monosaccharides
Figure 7.22 b-D-fructofuranose
Fructose (D-Fructose) is often referred to as fruit
sugar, because of its high content in fruit
On a per-gram basis, it is twice as sweet as sucrose;
therefore, it is often used as a sweetening agent in
processed food
Section 7.1: Monosaccharides
Figure 7.23 a-D-galactopyranose
Galactose is necessary to synthesize a variety of
important biomolecules
Important biomolecules include lactose, glycolipids,
phospholipids, proetoglycan, and glycoproteins
Galactosemia is a genetic disorder resulting from a
missing enzyme in galactose metabolism
Section 7.2: Disaccharides
Figure 7.27 Glycosidic Bonds
Disaccharides
Two monosaccharides linked by a glycosidic bond
Linkages are named by a- or b-conformation and by
which carbons are connected (e.g., a(1,4) or b(1,4))
Section 7.2: Disaccharides
Disaccharides Continued
Lactose (milk sugar) is the
disaccharide found in milk
One molecule of galactose linked to
one molecule of glucose (b(1,4)
linkage)
It is common to have a deficiency in
the enzyme that breaks down
lactose (lactase)
Lactose is a reducing sugar
Figure 7.28 a- and b-lactose
Section 7.2: Disaccharides
Disaccharides Continued
Sucrose is common table sugar
(cane or beet sugar) produced in
the leaves and stems of plants
One molecule of glucose linked to
one molecule of fructose, linked by
an a,b(1,2) glycosidic bond
Glycosidic bond occurs
between both anomeric carbons
Sucrose is a nonreducing sugar
Figure 7.31 Sucrose
Section 7.3: Polysaccharides
Polysaccharides (glycans) are composed of large
numbers of monosaccharides connected by glycosidic
linkages
Smaller glycans made of 10 to 15 monomers called
oligosaccharides, most often attached to polypeptides
as glycoproteins
Two broad classes: N- and O-linked oligosaccharides
Section 7.3: Polysaccharides
N-linked
oligosaccharides
are attached to
polypeptides by
an N-glycosidic
bond with the
side chain amide
nitrogen from the
amino acid
asparagine
Three major
types of
asparagine-linked
oligosaccharides:
high mannose,
hybrid, and
complex
O-Glycosidic
linkages
attach glycans
to the side
chain hydroxyl
of serine or
threonine
residues or the
hydroxyl
oxygens of
membrane
lipids
Figure 7.32 Oligosaccharides
Linked to Polypeptides
Section 7.3: Polysaccharides
Homoglycans
Have one type of monosaccharide and are found in
starch, glycogen, cellulose, and chitin (glucose
monomer)
Starch and glycogen are energy storage molecules
while chitin and cellulose are structural
Chitin is part of the cell wall of fungi and arthropod
exoskeleton
Cellulose is the primary component of plant cell
walls
No fixed molecular weight, because the size is a
reflection of the metabolic state of the cell producing
them
Section 7.3: Polysaccharides
Figure 7.33 Amylose
Starch—the energy reservoir of plant cells and a
significant source of carbohydrate in the human diet
Two polysaccharides occur together in starch:
amylose and amylopectin
Amylose is composed of long, unbranched chains of Dglucose with a(1,4) linkages between them
Section 7.3: Polysaccharides
Figure 7.33 Amylose
Amylose typically contains thousands of glucose
monomers and a molecular weight from 150,000 to
600,000 Da
The other form is amylopectin, which is a branched
polymer containing both a(1,6) and a(1,4) linkages
Branch points occur every 20 to 25 residues
Section 7.3: Polysaccharides
Glycogen is the carbohydrate storage molecule in
vertebrates found in greatest abundance in the liver
and muscle cells
Up to 8–10% of the wet weight of liver cells and 2–3%
in muscle cells
Similar in structure to amylopectin, with more branch
points
More compact and easily mobilized than other
polysaccharides
Section 7.3: Polysaccharides
Figure 7.34 (a) Amylopectin
and (b) Glycogen
Section 7.3: Polysaccharides
Figure 7.35 The
Disaccharide Repeating
Unit of Cellulose
Cellulose is a polymer of D-glucopyranosides linked
by b(1,4) glycosidic bonds
It is the most important structural polysaccharide of
plants (most abundant organic substance on earth)
Section 7.3: Polysaccharides
Figure 7.36 Cellulose
Microfibrils
Pairs of unbranched cellulose molecules (12,000
glucose units each) are held together by hydrogen
bonding to form sheetlike strips, or microfibrils
Each microfibril bundle is tough and inflexible with a
tensile strength comparable to that of steel wire
Important for dietary fiber, wood, paper, and textiles
Section 7.3: Polysaccharides
Heteroglycans
High-molecular-weight carbohydrate polymers that
contain more than one type of monosaccharide
Major types: N- and O-linked glycosaminoglycans
(glycans), glycosaminoglycans, glycan components of
glycolipids, and GPI (glycosylphosphatidylinositol)
anchors
GPI anchors and glycolipids will be discussed in
Chapter 11
Section 7.3: Polysaccharides
Heteroglycans Continued
N- and O-Glycans—many proteins have N- and Olinked oligosacchaarides
N-linked (N-glycans) are linked via a b-glycosidic bond
O-linked (O-glycans) have a disaccharide core of
galactosyl-b-(1,3)-N-acetylgalactosamine linked via an
a-glycosidic bond to the hydroxyl of serine or threonine
residues
Glycosaminoglycans (GAGs) are linear polymers with
disaccharide repeating units
Five classes: hyaluronic acid, chondroitin sulfate,
dermatan sulfate, heparin and heparin sulfate, and
keratin sulfate
Varying uses based on repeating unit
Section 7.4: Glycoconjugates
Glycoconjugates result from
carbohydrates being linked
to proteins and lipids
Proteoglycans
Distinguished from other
glycoproteins by their high
carbohydrate content (about
95%)
Occur on cell surfaces or
are secreted to the
extracellular matrix
Figure 7.38 Proteoglycan Aggregate
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press
Section 7.4: Glycoconjugates
Glycoproteins
Commonly defined as proteins that are covalently
linked to carbohydrates through N- and O-linkages
Several addition reactions in the lumen of the
endoplasmic reticulum and Golgi complex are
responsible for final N-linked oligosaccharide structure
O-glycan synthesis occurs later, probably initiating in
the Golgi complex
Carbohydrate could be 1%–85% of total weight
Glycoprotein Functions occur in cells as soluble and
membrane-bound forms and are nearly ubiquitous in
living organisms
Vertebrate animals are particularly rich in
glycoproteins
Section 7.4: Glycoconjugates
Figure 7.39 The Glycocalyx
Section 7.5: The Sugar Code
Living organisms require large coding capacities
for information transfer
Profound complexity of functioning systems
To succeed as a coding mechanism, a class of
molecules must have a large capacity for variation
Glycosylation is the most important
posttranslational modification in terms of coding
capacity
More possibilities with hexasaccharides than
hexapeptides
Section 7.5: The Sugar Code
In addition to their immense combinatorial
possibilities they are also relatively inflexible, which
makes them perfect for precise ligand binding
Lectins
Lectins, or carbohydrate-binding proteins, are
involved in translating the sugar code
Bind specifically to carbohydrates via hydrogen
bonding, van der Waals forces, and hydrophobic
interactions
Section 7.5: The Sugar Code
Lectins Continued
Biological processes
include binding to
microorganisms,
binding to toxins, and
involved in leukocyte
rolling
Figure 7.40 Role of Oligosaccharides in
Biological Recognition
Section 7.5: The Sugar Code
The Glycome
Total set of sugars and glycans in a cell or organism
is the glycome
Constantly in flux depending on the cell’s response
to environment
There is no template for glycan biosynthesis; it is
done in a stepwise process
Glycoforms can result based upon slight variations
in glycan composition of each glycoprotein
Chapter 11
Lipids and Membranes
Section 11.1: Lipid Classes
Figure 11.1 Fatty
Acid Structure
Fatty Acids
Monocarboxylic acids that typically contain
hydrocarbon chains of variable lengths (12 to 20 or
more carbons)
Numbered from the carboxylate end, and the acarbon is adjacent to the carboxylate group
Terminal methyl carbon is denoted the omega (w)
carbon
Important in triacylglycerols and phospholipids
Section 11.1: Lipid Classes
Section 11.1: Lipid Classes
Most naturally occurring fatty acids
have an even number of carbons in an
unbranched chain
Fatty acids that contain only single
carbon-carbon bonds are saturated
Fatty acids that contain one or more
double bonds are unsaturated
Figure 11.2 Isomeric
Forms of Unsaturated
Molecules
Can occur in two isomeric forms: cis
(like groups on the same side) and trans
(like groups are on opposite sides)
Section 11.1: Lipid Classes
Figure 11.3 Space-Filling and
Conformational Models
The double bonds in most naturally occurring fatty
acids are cis and cause a kink in the fatty acid chain
Unsaturated fatty acids are liquid at room
temperature; saturated fatty acids are usually solid
Monounsaturated fatty acids have one double bond
while polyunsaturated fats have two or more
Section 11.1: Lipid Classes
Plants and bacteria can synthesize all fatty acids
they require from acetyl-CoA
Animals acquire most of theirs from dietary sources
Nonessential fatty acids can be synthesized while
essential fatty acids must be acquired from the diet
Omega-3 fatty acids (i.e., a-linolenic acid and its
derivatives) may promote cardiovascular health
Certain fatty acids attach to proteins called acylated
proteins; the groups (acyl groups) help facilitate
interactions with the environment
Myristoylation and palmitoylation
Section 11.1: Lipid Classes
Eicosanoids
Figure 11.4a Eicosanoids
A diverse group of powerful, hormone-like (generally
autocrine) molecules produced in most mammalian
tissues
Include prostaglandins, thromboxanes, and
leukotrienes
Mediate a wide variety of physiological processes:
smooth muscle contraction, inflammation, pain
perception, and blood flow regulation
Section 11.1: Lipid Classes
Figure 11.4a Eicosanoids
Eicosonoids are often derived from arachidonic acid
or eicosapentaenoic acid (EPA)
Prostaglandins contain a cyclopentane ring and
hydroxyl groups at C-11 and C-15
Prostaglandins are involved in inflammation,
digestion, and reproduction
Section 11.1: Lipid Classes
Figure 11.4b Eicosanoids
Thromboxanes differ structurally from other
eicosanoids in that they have a cyclic ether
Synthesized by polymorphonuclear lymphocytes
Involved in platelet aggregation and vasoconstriction
following tissue injury
Section 11.1: Lipid Classes
Figure 11.4c Eicosanoids
Leukotrienes were named from their discovery in
white blood cells and triene group in their structure
LTC4, LTD4, and LTE4 have been identified as
components of slow-reacting substance of anaphylaxis
Other effects of leukotrienes: blood vessel fluid
leakage, white blood cell chemoattractant,
vasoconstriction, edema, and bronchoconstriction
Section 11.1: Lipid Classes
Figure 11.5 Triacylglycerol
Triacylglycerols
Triacylglycerols are esters of glycerol with three fatty
acids
Neutral fats because they have no charge
Contain fatty acids of varying lengths and can be a
mixture of saturated and unsaturated
Section 11.1: Lipid Classes
Depending on fatty acid
composition, can be termed
fats or oils
Figure 11.6 Space-Filling and
Conformational Models of a
Triacylglycerol
Fats are solid at room
temperature and have a high
saturated fatty acid
composition
Oils are liquid at room
temperature and have a high
unsaturated fatty acid
composition
Section 11.1: Lipid Classes
Figure 11.5 Triacylglycerol
Roles in animals: energy storage (also in plants),
insulation at low temperatures, and water repellent
for some animals’ feathers and fur
Better storage form of energy for two reasons:
1. Hydrophobic and coalesce into droplets; store an
equivalent amount of energy in about one-eighth the
space
2. More reduced and thus can release more electrons
per molecule when oxidized
Section 11.1: Lipid Classes
Figure 11.8 The Wax Ester
Melissyl Cerotate
Wax Esters
Waxes are complex mixtures of nonpolar lipids
Protective coatings on the leaves, stems, and fruits
of plants and on the skin and fur of animals
Wax esters composed of long-chain fatty acids and
long-chain alcohols are prominent constituents of
most waxes
Examples include carnuba (melissyl cerotate) and
beeswax
Section 11.1: Lipid Classes
Figure 11.9 Phospholipid
Molecules in Aqueous
Solution
Phospholipids
Amphipathic with a polar head group (phosphate and
other polar or charged groups) and hydrophobic fatty
acids
Act in membrane formation, emulsification, and as a
surfactant
Spontaneously rearrange into ordered structures when
suspended in water
Section 11.1: Lipid Classes
Two types of phospholipids: phosphoglycerides and
sphingomyelins
Sphingomyelins contain sphingosine instead of
glycerol (also classified as sphingolipids)
Phosphoglycerides contain a glycerol, fatty acids,
phosphate, and an alcohol
Simplest phosphoglyceride is phosphatidic acid
composed of glycerol-3-phosphate and two fatty
acids
Phosphatidylcholine (lecithin) is an example of
alcohol esterified to the phosphate group as choline
Section 11.1: Lipid Classes
Section 11.1: Lipid Classes
Another phosphoglyceride,
phosphatidylinositol, is an
important structural
component of glycosyl
phosphatidylinositol (GPI)
anchors
GPI anchors attach
certain proteins to the
membrane surface
Proteins are attached
via an amide linkage
Figure 11.10 GPI Anchor
Section 11.1: Lipid Classes
Figure 11.11 Phospholipases
Phospholipases
Hydrolyze ester bonds in glycerophospholipid
molecules
Three major functions: membrane remodeling, signal
transduction, and digestion
Membrane remodeling—removal of fatty acids to
adjust the ratio of saturated to unsaturated or
repair a damaged fatty acid
Section 11.1: Lipid Classes
Phospholipases Continued
Signal Transduction—phospholipid hydrolysis
initiates the signal transduction by numerous
hormones
 Digestion—pancreatic phospholipases degrade
dietary phospholipids in the small intestine
Toxic Phospholipases—various organisms use
membrane-degrading phospholipases as a means of
inflicting damage
Bacterial a-toxin and necrosis from snake
venom (PLA2)
Section 11.1: Lipid Classes
Figure 11.12 Sphingolipid Components
Sphingolipids
Important components of animal and plant
membranes
Sphingosine (long-chain amino alcohol) and ceramide
in animal cells
Section 11.1: Lipid Classes
Sphingomyelin is found in
most cell membranes, but is
most abundant in the myelin
sheath of nerve cells
Figure 11.13 Space-Filling and
Conformational Models of
Sphingolmyelin
Section 11.1: Lipid Classes
Figure 11.14a Selected
Glycolipids
The ceramides are also precursors of glycolipids
A monosaccharide, disacchaaride, or oligosaccharide
attached to a ceramide through an O-glycosidic bond
Most important classes are cerebrosides, sulfatides,
and gangliosides (may bind bacteria and their toxins)
Section 11.1: Lipid Classes
Figure 11.14b Selected Glycolipids
Cerebrosides have a monosaccharide for their head
group
Galactocerebroside is found in brain cell
membranes
Sulfatides are negatively charged at physiological pH
Gangliosides possess oligosaccharide groups; occur in
most animal tissues and GM2 is involved in Tay-Sachs
disease
Section 11.1: Lipid Classes
Figure 11.15
Isoprene
Isoprenoids
Vast array of biomolecules containing repeating fivecarbon structural units, or isoprene units
Isoprenoids consist of terpenes and steroids
Terpenes are classified by the number of isoprene
units they have
Monoterpenes (used in perfumes), sesquiterpines (e.g.,
citronella), tetraterpenes (e.g., carotenoids)
Section 11.1: Lipid Classes
Figure 11.16 Vitamin K, a
Mixed Terpenoid
Carotenoids are the orange pigments found in plants
Mixed terpenoids consist of a nonterpene group
attached to the isoprenoid group (prenyl groups)
Include vitamin K and vitamin E
Section 11.1: Lipid Classes
Figure 11.17 Prenylated
Proteins
A variety of proteins are covalently attached to prenyl
groups (prenylation): farnesyl and geranylgeranyl
groups
Unknown function, but may be involved in cell
growth
Section 11.1: Lipid Classes
Figure 11.18 Structure
of Cholesterol
Steroids are derivatives of triterpenes with four fused
rings (e.g., cholesterol)
Found in all eukaryotes and some bacteria
Differentiated by double-bond placement and various
substituents
Section 11.1: Lipid Classes
Cholesterol is an important molecule in animal cells
that is classified as a sterol, because C-3 is oxidized to a
hydroxyl group
Essential in animal membranes; a precursor of all
steroid hormones, vitamin D, and bile salts
Usually stored in cells as a fatty acid ester
The term steroid is commonly used to describe all
derivatives of the steroid ring structure
Section 11.1: Lipid Classes
Figure 11.19 Animal Steroids
Section 11.1: Lipid Classes
Lipoproteins
Figure 11.21 Plasma
Lipoproteins
Term most often applied to a
group of molecular complexes
found in the blood plasma of
mammals
Transport lipid molecules
through the bloodstream from
organ to organ
Protein components
(apolipoproteins) for lipoproteins
are synthesized in the liver or
intestine
Section 11.1: Lipid Classes
Lipoproteins are classified according to their density:
Chylomicrons are large lipoproteins of extremely low
density that transport triacylglycerol and cholesteryl
esters (synthesized in the intestines)
Very low density lipoproteins (VLDL) are synthesized
in the liver and transport lipids to the tissues
Low density lipoproteins (LDL) are principle
transporters of cholesterol and cholesteryl esters to
tissues
High density lipoprotein (HDL) is a protein-rich
particle produced in the liver and intestine that seems
to be a scavenger of excess cholesterol from membranes
Section 11.2: Membranes
A membrane is a noncovalent heteropolymer of lipid
bilayer and associated proteins (fluid mosaic model)
Membrane Structure
Proportions of lipid, protein, and carbohydrate vary
considerably among cell types and organelles
Section 11.2: Membranes
Figure 11.25 Lateral
Diffusion in Biological
Membranes
Membrane lipids: phospholipids form bimolecular
layers at relatively low concentrations; this is the
basis of membrane structure
Membrane lipids are largely responsible for many
membrane properties
Membrane fluidity refers to the viscosity of the lipid
bilayer
Rapid lateral movement is apparently responsible for
normal membrane function
Section 11.2: Membranes
The movement of molecules
from one side of a membrane
to the other requires a
flipase
Membrane fluidity largely
depends on the percentage of
unsaturated fatty acids and
cholesterol
Cholesterol contributes
to stability with its rigid
ring system and fluidity
with its flexible
hydrocarbon tail
Figure 11.24 Diagrammatic View of
a Lipid Bilayer
Section 11.2: Membranes
Selective permeability is provided by the hydrophobic
chains of the lipid bilayer, which is impermeable to
most all molecules (except small nonpolar molecules)
Membrane proteins help regulate the movement of
ionic and polar substances
Small nonpolar substances may diffuse down their
concentration gradient
Self-sealing is a result of the lateral flow of lipid
molecules after a small disruption
Asymmetry of biological membranes is necessary for
their function
The lipid composition on each side of the membrane
is different
Section 11.2: Membranes
Figure 11.26 Integral and
Peripheral Membrane Proteins
Membrane Proteins—most functions associated with
the membrane require membrane proteins
Classified by their relationship with the membrane:
peripheral or integral
Section 11.2: Membranes
Figure 11.27 Red Blood Cell
Integral Membrane Proteins
Integral proteins embed in
or pass through the
membrane
Red blood cell anion
exchanger
Peripheral proteins are
bound to the membrane
primarily through
noncovalent interactions
Can be linked covalently
through myristic, palmitic, or
prenyl groups
GPI anchors link a wide
variety of proteins to the
membrane
Section 11.2: Membranes
Figure 11.28 Lipid Rafts
Membrane Microdomains—lipids and proteins in
membranes are not uniformly distributed
Specialized microdomains like “lipid rafts” can be
found in the external leaflet of the plasma membrane
Section 11.2: Membranes
Figure 11.29 The Lipid
Raft Environment
Lipid rafts often include cholesterol, sphingolipids, and
certain proteins
Lipid molecules are more ordered (less fluid) than nonraft regions
Lipid rafts have been implicated in a number of
processes: exocytosis, endocytosis, and signal
transduction
Section 11.2: Membranes
Figure 11.30 Transport
across Membranes
Membrane Function
There are a vast array of membrane functions,
including transport of polar and charged substances
and the relay of signals
Section 11.2: Membranes
Membrane Transport—the mechanisms are vital to
living organisms
Ions and molecules constantly move across the
plasma membrane and membranes of organelles
Important for nutrient intake, waste excretion,
and the regulation of ion concentration
Biological transport mechanisms are classified according
to whether they require energy
Section 11.2: Membranes
Figure 11.30 Transport
across Membranes
In passive transport, there is no energy input, while
in active transport, energy is required
Passive is exemplified by simple diffusion and
facilitated diffusion (with the concentration gradient)
Active transport uses energy to transport molecules
against a concentration gradient
Section 11.2: Membranes
Simple diffusion involves the propulsion of each solute
by random molecular motion from an area of high
concentration to an area of low concentration
Diffusion of gases O2 and CO2 across membranes is
proportional to their concentration gradients
Does not require a protein channel
Facilitated diffusion uses channel proteins to move
large or charged molecules down their concentration
gradient
Examples include chemically gated Na+ channel
and voltage-gated K+ channel
Section 11.2: Membranes
Figure 11.31 The Na+-K+ ATPase
and Glucose Transport
Active transport has two forms: primary and secondary
In primary active transport, transmembrane ATPhydrolyzing enzymes provide the energy to drive the
transport of ions or molecules
Na+-K+ ATPase
Section 11.2: Membranes
Figure 11.31 The Na+-K+ ATPase
and Glucose Transport
In secondary active transport, concentration
gradients formed by primary active transport are
used to move other substances across the membrane
Na+-K+ ATPase pump in the kidney drives the
movement of D-glucose against its concentration
gradient
Section 11.2: Membranes
Membrane Receptors provide mechanisms by
which cells monitor and respond to changes in their
environment
Chemical signals bind to membrane receptors in
multicellular organisms for intracellular
communication
Other receptors are involved in cell-cell recognition
Binding of ligand to membrane receptor causes a
conformational change and programmed response