1 The flow of biological information DNA RNA Protein Cell Structure and Function Noncovalent Bonds Storage of Biological Information in DNA Transfer of

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The flow of biological The flow of biological informationinformation

DNA RNA Protein Cell Structure and FunctionDNA 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

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 Biochemistry and communicationcommunication

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.

DNADNA - information storage

RNARNA - information retrieval

ProteinProtein - information processing

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Communication between cellsCommunication 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 signal transductiontransduction.

• Regulation of glucose is a good example.

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Communication between Communication between organisms.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 | ||

CH3CHCH2CH2OCCH3

CH3CH2CH=CH(CH2)9CH2OCCH3

isoamyl acetate(honey bee alarm)

tetradecenyl acetate(european corn borer

sex pheromone)

O ||

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Biological and noncovalent Biological and noncovalent interactionsinteractions

• 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.

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Common properties of Common properties of noncovalent bondsnoncovalent bonds

Three common characteristics.

Forces are relatively weak and noncovalent.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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The bonding process is reversible.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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Binding is specificBinding 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.

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Storage of biological informationStorage of biological information

Total genetic content in a cell is called the genomegenome.

This information is stored in a long, coiled DNA molecule.

It is used two ways.It is used two ways.Duplication during cell divisionManufacture of RNA

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DNA moleculeDNA molecule

Consists of a long, unbranched hetropolymerhetropolymer - more than one type of monomer unit.

deoxyribose

phosphate

nitrogen base (4 types)

O|

O -- P -- O --||O

- CH2 O

OH

O|

O -- P -- O --||O

- CH2 O

O|

O -- P -- O --||O

- CH2 O

O-

| O -- P -- O --

||O

- CH2 O

NC

C

CCN

N

N

CH

NH2

|

H

NC

C

CCNO

NH2

|

H

H

NC

C

CCN

N

N

CH

O||

H

H2N

NC

C

CCNO

H

H

O|| CH3

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NC

C

CCN

N

NH

CH

NH2

|

H

NC

C

CCN

N

NH

CH

O||

H

H2N

adenineadenine guanineguanine

NC

C

CCNH

O

NH2

|

H

H NC

C

CCNH

O

H

H

O|| CH3

cytosinecytosine thyminethymine

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Strands form complementary base pairs.

The entire human genome takes 1 meter of DNA - 3 billion base pairs.

G

T

C

A

C G

A

C

T

G

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DNA replicationDNA 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 semiconservativesemiconservative since each new DNA molecule contains one new and one original strand.

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DNA replicationDNA replication

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Why DNA?Why DNA?

DNA is a very stable moleculeDNA is a very stable moleculeSurvives 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 Transfer of biological informationinformation

TranscriptionTranscriptionProduction 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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TranscriptionTranscription

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 RNATypes 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)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)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)Transfer RNA (tRNA)

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Messenger RNA (mRNA)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.

mRNAribosome

5’end

3’end

growingpeptide

completepeptide

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Protein synthesisProtein synthesis

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 translationtranslation.

tRNA

rRNA

DNA mRNA protein

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The genetic codeThe 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 IntronsExons 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.

exonsexons coding regions of DNA

intronsintrons noncoding regions of DNA

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ExonsExons• Contain 120-150 bases used to represent

a 40 - 50 amino acid sequence.

IntronsIntrons

• 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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• Newly synthesized mRNA is longer than the final, mature form.

• Final form is the result of extensive post-processing 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 processingErrors in DNA processing

DNA mutationsDNA mutationsMillions of years of evolution have resulted in replication, transcription and translation processes that are highly accurate.

Errors can still occur - mutationsmutations - at a rate of about 1 error/109 nucleotides.

Mechanisms to repair mutations have also evolved.

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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 anemiaOne example - sickle cell anemiaOnly two “incorrect” amino acids out

of 546 in hemoglobin. Results in a very significant change.

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Normal SickleHemoglobin

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Signal transduction Signal transduction through cell membranesthrough cell membranes

Information transfer by signal transduction.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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Examples of ‘signal’ moleculesExamples of ‘signal’ molecules

ProstaglandinsProstaglandinsControl many functions like contraction of smooth muscles and blood platelet aggregation.

Insulin and GlucagonInsulin and GlucagonGlucose regulation.

Sex hormonesSex hormonesSecondary sex characteristics.

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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 proteinBinding site protein

G proteinG protein

Adenylate cyclaseAdenylate cyclase

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Steps in signal transductionSteps in signal transduction

Hormone is picked up by the target cell because it contains a receptor site to accept it (binding protein)

G

extracellular fluid

adenylatecyclase

cytoplasm

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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).

G

GTP GDP

extracellular fluid

adenylatecyclase

cytoplasm

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Activated G protein passes signal to an enzyme (typically adenylate cyclase) which either stimulates or inhibits it.

G

extracellular fluid

adenylatecyclase

cytoplasm

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Adenylate cyclase catalyzes the formation of cyclic adenosine 3’,5’-monophosphate (cAMP) from ATP.

G

ATP

cAMP

extracellular fluid

adenylatecyclase

cytoplasm

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cAMP then goes on to do whatever it is required to do. It acts as a secondary, short-lived messenger.

G

cAMP

inactiveprotein

activeprotein

cellularresponse

extracellular fluid

adenylatecyclase

cytoplasm

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Control of glucose levelsControl of glucose levels

InsulinInsulin

• 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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High glucoselevel

Productionof insulin

in pancreas

Insulinbinds to site

on cell membranewhich allows

glucose to enter

Glucose can then beused by the cell

or stored as glycogen (liver or skeletal

muscles).

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GlucagonGlucagon

• 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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Low glucoselevel

Productionof glucagonin pancreas

glucagonTargetssite on

liver cell membrane(adenylate cyclase)

Glucagon starts processthat converts

glycogen to glucose

glucose enters blood

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EpinephrineEpinephrine

• 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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Approach oflarge carnivorous

animal!

Productionof epinephrine

by adrenal gland

epinephrineTargetssite on

muscle cellmembrane

epinephrine startsprocess

that convertsglycogen to glucose

glucose enters blood

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Characteristics of Characteristics of signal transductionsignal transduction

Chemical signal that results from hormone Chemical signal that results from hormone binding is amplified.binding is amplified. Many molecules of cAMP can be produced from a single hormone signal

Hormones are usually released by the Hormones are usually released by the endocrine system on demand.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 Diseases of cellular communicationcommunication

Example - Cholera toxinExample - Cholera toxinInterferes 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 Diseases of cellular communicationcommunication

Work is being conducted to develop new drugs - three approaches

Function at DNA levelFunction at DNA levelBlock transcription of disease genes.Interfere with translation of mRNA.

Bind to receptor proteinsBind to receptor proteinsBlock toxins, viruses ...

Interfere with signaling pathways in cellInterfere with signaling pathways in cellSmall, nonpolar chemicals that inhibit proteins involved in signaling process.

Documents

1 The flow of biological information DNA RNA Protein Cell Structure and Function Noncovalent Bonds Storage of Biological Information in DNA Transfer of