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The flow of biological information
DNA
RNA
Protein
Cell Structure and Function
Noncovalent Bonds
Storage of Biological Information in DNA
Transfer of Biological Information to RNA
Protein Synthesis
Errors in DNA Processing
Signal Transduction through Cell
Membranes
Diseases of Cellular Communication
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Biochemistry and communication
Much study on how cells and organisms
communicate - hormones, pheromones,
neurotransmitters.
DNA, RNA, proteins and other large
molecules contain much information that
is need for cellular processes.
DNA
- information storage
RNA
- information retrieval
Protein
- information processing
2
Communication between cells
• Multicellular organisms need a way to
coordinate activities between cells.
• Most cells produce and secrete molecules
to pass information to others - cause an
effect on a target cell site.
• The most common mechanism for
transmembrane communication is signal
transduction.
• Regulation of glucose is a good example.
3
Communication between organisms.
• One or more chemicals are released to the
environment by an organism.
• Other organisms can detect these
chemicals at very low levels.
• Pheromones are a well known examples.
CH3
O
isoamyl acetate
CH3CHCH2CH2OCCH3 (honey bee alarm)
|
tetradecenyl acetate
(european corn borer
sex pheromone)
||
O
||
CH3CH2CH=CH(CH2)9CH2OCCH3
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Biological and noncovalent
interactions
• DNA, RNA, proteins and some
carbohydrates are informational
molecules.
• Information is retrieved by ‘reading’ the
sequence of monomeric units in them
(molecular recognition).
• Noncovalent forces are used to read this
information - van der Waal’s, ionic,
hydrogen and hydrophobic interactions.
5
Common properties of
noncovalent bonds
Three common characteristics.
Forces are relatively weak and noncovalent.
1-30 kJ/mol, compared to the 350 kJ/mol
for a C-C single bond.
Single interactions are typically not
sufficient to hold two species together.
Several such interactions can participate at
the same time.
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Common properties of
noncovalent bonds
The bonding process is reversible.
Molecules diffuse and will come close
enough for contact.
Thermal motion assists in making the
proper contact.
It does not last more than a few seconds.
Additional thermal motion will cause the
intermediate form to ‘fall apart.’
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Common properties of
noncovalent bonds
Binding is specific
Due to the size and shapes of the
molecules, only certain species are able
to align properly.
Complementary noncovalent interactions
are also required.
Size, shape and type of interaction all
must be correct for binding.
8
Storage of biological information
Total genetic content in a cell is called the
genome.
This information is stored in a long, coiled
DNA molecule.
It is used two ways.
Duplication during cell division
Manufacture of RNA
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DNA molecule
Consists of a long, unbranched hetropolymer
- more than one type of monomer unit.
NH2
|
C
N
deoxyribose
phosphate
C
N
CH
OHC
C
N
N
-O -- P| -- O --CH
NH
2 O
|
C
||
N
CH
O
O
C
CH
O
N
|
-O -- P -- O --CH
O
2 O
||
C
N
||
HN
C
CH
O
O
C
C
N
HN
N
-O -- P| -- O --CH
2 O
||
HN
O
O
C
O
|
-O -- P -- O --CH
2 O
||
O
OH
2
2
nitrogen base
(4 types)
O
||
C
CH3
C
CH
N
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DNA molecule
NH2
|
C
N
O
||
C
adenine
N
C
guanine
HN
N
C
CH
HC
C
CH
HN
C
CH
C
O
N
H
N
thymine
O
||
C
N
N
H
C
H2N
cytosine
NH2
|
C
O
C
N
H
N
CH
CH3
C
CH
N
H
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DNA molecule
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DNA molecule
Strands form
complementary
base pairs.
The entire human
genome takes 1
meter of DNA 3 billion base
pairs.
C
G
T
A
G
C
C
G
A
T
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DNA replication
This is a self-directed process that relies on
many “accessory” proteins.
Each strand serves as a template during
replication by unwinding in small regions.
DNA polymerase is used to covalently link
the DNA backbone.
This is semiconservative since each new
DNA molecule contains one new and one
original strand.
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DNA replication
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Why DNA?
DNA is a very stable molecule
Survives under extracellular conditions.
Covalent backbone is chemically stable in
aqueous environments.
Sixty five million year old dinosaur
samples and 120 million year old weevil
samples have been found to still contain
large amounts of DNA.
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Transfer of biological information
Transcription
Production of RNA from DNA.
Only a small portion of a DNA strand is
actually used during a transcription.
Much of DNA’s information is used to
make RNA but not all of it.
Some traits are not expressed.
Some regions in prokaryotic cells are
not usable.
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Transcription
Production of RNA is similar to DNA
replication. The differences are:
• Ribonucleotides are used.
• Uracil replaces thymine.
• RNA:DNA hybrid duplex product
eventually unravels and RNA is released.
• RNA polymerase is used to link
nucleotides.
• The product is a single-strand species.
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Types of RNA
There are three types of RNA. All share
some common properties.
• All are single strands.
• All are produced by DNA transcription
using RNA polymerase (except RNA
viruses).
• All play roles in protein synthesis.
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Ribosomal RNA (rRNA)
The most abundant type of RNA.
A combination of protein and rRNA
molecules is used to form ribosomes.
These are the sites of protein synthesis.
Multiple RNA strands are used in each
ribosome.
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Transfer RNA (tRNA)
The smallest type of RNA molecule,
consisting of 73-93 nucleotides.
They combine with amino acids and act to
transport them to the site of protein
synthesis.
At least one type of tRNA for each
amino acid.
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Transfer RNA (tRNA)
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Messenger RNA (mRNA)
The information from a single gene.
The ‘tape’ that is read by the ribosome
when producing a protein.
It is unstable and rapidly decays.
mRNA
ribosome
3’
end
5’
end
complete
peptide
growing
peptide
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Protein synthesis
tRNA
DNA
mRNA
protein
rRNA
mRNA is the intermediate carrier of DNA
information.
It is a linear sequence of bases used to make
a sequence of amino acids - protein.
The process is called translation.
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The genetic code
The order of bases in DNA will specify
which amino acids are used in a protein.
• Triplet code - three bases are needed to specify
an amino acid.
• The sets of three bases are nonoverlapping and
read sequentially.
• An amino acid may have more than one code
(degenerate), but no amino acids share the same
code.
• Stop and start codes are also used.
• Code is nearly universal for all life.
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Exons and Introns
In prokaryotic cells, DNA is read from “start”
to “stop”, producing mRNA.
For eukaryotic cells, sections of mRNA are
removed prior to producing protein.
It appears that DNA contains noncoding
regions.
exons
coding regions of DNA
introns
noncoding regions of DNA
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Exons and Introns
Exons
• Contain 120-150 bases used to represent
a 40 - 50 amino acid sequence.
Introns
• 50 - 20,000 bases.
• Purpose is unknown; may be evolutionary
“junk DNA.”
• Absent in prokaryotes, rare in lower
eukaryotic cells like yeast.
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Exons and Introns
• Newly synthesized mRNA is longer than
the final, mature form.
• Final form is the result of extensive postprocessing to remove regions produced
from intron regions.
• Maturing of mRNA may require several
accessory enzymes.
• It’s not uncommon for a gene to contain
two or more introns.
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Errors in DNA processing
DNA mutations
Millions of years of evolution have
resulted in replication, transcription and
translation processes that are highly
accurate.
Errors can still occur - mutations - at a
rate of about 1 error/109 nucleotides.
Mechanisms to repair mutations have also
evolved.
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Errors in DNA processing
The effect of mutation is based on the area
where it occurs.
For intron region, it has no real effect.
If it occurs in an exon region, it may alter
the amino acid sequence of a protein.
One example - sickle cell anemia
Only two “incorrect” amino acids out of
546 in hemoglobin. Results in a very
significant change.
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Errors in DNA processing
Normal
Sickle
Hemoglobin
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Signal transduction
through cell membranes
Information transfer by signal transduction.
• Many biological activities require precise
coordination - both in and between cells.
• The more highly developed the organism, the
greater the need for coordination. Different
organs take on specific roles.
• Chemicals like hormones and growth factors are
used by one cell to alter the activities of another.
• Target cells use receptors on their surface to
recognize signal molecules.
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Signal transduction
through cell membranes
Examples of ‘signal’ molecules
Prostaglandins
Control many functions like contraction of
smooth muscles and blood platelet
aggregation.
Insulin and Glucagon
Glucose regulation.
Sex hormones
Secondary sex characteristics.
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Signal transduction
through cell membranes
The process used for transduction will vary
for each hormone.
Each will follow a general series of events.
At least three types of protein are used.
Binding site protein
G protein
Adenylate cyclase
34
Steps in signal transduction
extracellular fluid
Hormone is
picked up by the
target cell
because it
contains a
receptor site to
accept it
(binding protein)
G
adenylate
cyclase
cytoplasm
35
Steps in signal transduction
extracellular fluid
Binding stimulates
the receptor site
to interact with a
G protein in the
inner membrane.
“G” because the
protein will bind
guanine nucleotides
(GDP, GTP).
adenylate
cyclase
G
GTP
GDP
cytoplasm
36
Steps in signal transduction
extracellular fluid
Activated G protein
passes signal to an
enzyme (typically
adenylate cyclase)
which either
stimulates or
inhibits it.
G
adenylate
cyclase
cytoplasm
37
Steps in signal transduction
extracellular fluid
Adenylate cyclase
catalyzes the
formation of cyclic
adenosine 3’,5’monophosphate
(cAMP) from ATP.
G
adenylate
cyclase
ATP
cAMP
cytoplasm
38
Steps in signal transduction
extracellular fluid
cAMP then goes on
to do whatever it is
required to do. It
acts as a
secondary, shortlived messenger.
adenylate
cyclase
G
cellular
response
cytoplasm
active
protein
cAMP
inactive
protein
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Control of glucose levels
Insulin
• Hormone produced by the beta cells in
the pancreas.
• Stored as proinsulin (inactive form) as
small granules.
• Release is triggered by increased glucose
levels in the blood.
• Stimulates glucose uptake by tissue by
binding to receptors in the cell
membrane. Permits glucose to enter cell.
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Control of glucose levels
High glucose
level
Production
of insulin
in pancreas
Insulin
binds to site
on cell membrane
which allows
glucose to enter
Glucose can then be
used by the cell
or stored as glycogen
(liver or skeletal
muscles).
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Control of glucose levels
Glucagon
• This hormone is also produced in the
pancreas in an inactive form.
• Low glucose levels result in its conversion
to an active form and its release.
• Its entry into liver cells results in the
conversion of glycogen to glucose, with
glucose being released to the blood.
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Control of glucose levels
Low glucose
level
glucose enters blood
Production
of glucagon
in pancreas
glucagon
Glucagon starts process
that converts
glycogen to glucose
Targets
site on
liver cell membrane
(adenylate cyclase)
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Control of glucose levels
Epinephrine
• Adrenaline - ‘flight or fight hormone’
• Similar in effect to glucagon but affects
primarily muscle tissue.
• It also affects the nervous system.
• Results in a very rapid “all systems
ready.”
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Control of glucose levels
Approach of
large carnivorous
animal!
glucose enters blood
Production
of epinephrine
by adrenal gland
epinephrine
Targets
site on
muscle cell
membrane
epinephrine starts
process
that converts
glycogen to glucose
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Characteristics of
signal transduction
Chemical signal that results from hormone
binding is amplified.
Many molecules of cAMP can be produced
from a single hormone signal
Hormones are usually released by the
endocrine system on demand.
Not continuous - system can make changes
as needed. Rapid release and transient
existence provide for ability to respond
quickly.
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Diseases of cellular
communication
Example - Cholera toxin
Interferes with the normal action level of
G protein. Causes continuous activation
of adenylate cyclase.
Results in high cAMP levels in epithelial
cells of the intestine.
Causes uncontrolled release of water and
sodium, leading to diarrhea and
dehydration.
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Diseases of cellular
communication
Work is being conducted to develop new
drugs - three approaches
Function at DNA level
Block transcription of disease genes.
Interfere with translation of mRNA.
Bind to receptor proteins
Block toxins, viruses ...
Interfere with signaling pathways in cell
Small, nonpolar chemicals that inhibit
proteins involved in signaling process.
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