BCHM 3050 Lecture 10 DNA Structure.ppt

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Structure of DNA

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Definition & Classification

Nucleic Acid:

Linear polymers of

nucleotides

that

function in the storage and expression of

genetic information, and its transfer from

one generation to the next.

Two Main Types:

1 - Ribonucleic Acid (RNA)

2 - De-oxyribonucleic Acid (DNA)

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3

Molecular Components of Nucleotides

Three Components:

1) Nitrogenous Base 1) Nitrogenous Base 2) Pentose Sugar 2) Pentose Sugar 3) Phosphate

3) Phosphate

Phosphate

Ribose

Adenosine-5’-monophosphate

OH

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Pyrimidines:

Six-membered heterocyclic rings of C & N.

Purines:

Fused Six-membered + five-membered

heterocyclic rings of C & N.

Bases:

N-groups can accept protons, giving

“

basic

”

properties to the molecule.

Two Families of Nitrogenous Bases

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Common Purines & Pyrimidines

Purines

Pyrimidines

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Notes & Comments Re Nitrogenous Bases

Occurrence



A, T, C, G & U are main components of nucleic acids.



Xanthine & hypoxanthine . . .

– rarely occur (due to spontaneous deamination of G & A)._{rarely occur (due to spontaneous deamination of G & A).} – are removed during DNA repair._{are removed during DNA repair.}

– are intermediates in nucleotide catabolism._{are intermediates in nucleotide catabolism.}



U occurs only in RNA

’

s where it replaces T.

– DNA contains A,T,C,G._{DNA contains A,T,C,G.}

– RNA contains A,U,C,G._{RNA contains A,U,C,G.}

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Some Interesting Nitrogenous Bases



Theobromine & Theophylline

– Secondary metabolites of cocoa beans and tea leaves. _{Secondary metabolites of cocoa beans and tea leaves.} – Act as diuretic, cardiac stimulant, and esp. vasodilator – _{Act as diuretic, cardiac stimulant, and esp. vasodilator –}

relaxes smooth muscles (bronchiodilator for asthmatics). relaxes smooth muscles (bronchiodilator for asthmatics).



Caffeine

– Stimulant, diuretic. _{Stimulant, diuretic.}

– Antagonist to adenosine._{Antagonist to adenosine.}

Theobromine

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Nucleo

sides

Nitrogenous Bases Attached to Sugars

 Sugar is Ribose or 2-Deoxy-ribose (RNA vs. DNA).Sugar is Ribose or 2-Deoxy-ribose (RNA vs. DNA).

 Attachment via Attachment via -1-1N glycosidic bond.N glycosidic bond.

 Plane of base is Plane of base is  to plane of sugar. to plane of sugar.

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Common Ribonucleosides

Thymidine

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Adenosine

A Physiologically Active Nucleoside

 Inhibitory neurotransmitter synthesized in _{Inhibitory neurotransmitter synthesized in} the brain, binds to adenosine receptors. the brain, binds to adenosine receptors.

 Binding causes . . ._{Binding causes . . .}

– drowsiness (slows down nerve cell _{drowsiness (slows down nerve cell} activity).

activity).

– dilation of blood vessels (lets more _{dilation of blood vessels (lets more} oxygen in during sleep).

oxygen in during sleep).

 Clinically used as an anti-arrhythmic to _{Clinically used as an anti-arrhythmic to} “

“defibrillatedefibrillate”” abnormally fast heartbeats; abnormally fast heartbeats; used in cardiac stress tests.

used in cardiac stress tests.

 Caffeine competes with same (brain) _{Caffeine competes with same (brain)} receptor; reversing effects of adenosine. receptor; reversing effects of adenosine.

Adenosine

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Cordycepin (3

’

- Deoxy Adenosine)

A Physiologically Active Nucleoside

 Antibiotic produced by _{Antibiotic produced by}Cordyceps militarisCordyceps militaris

(the

(the ““Scarlet Caterpillar FungusScarlet Caterpillar Fungus””) – ) – parasitizes burried moth pupae. parasitizes burried moth pupae.

 _{Inhibits the final step of RNA biosynthesis}_{Inhibits the final step of RNA biosynthesis}

by termination of the ribonucleotide chain. by termination of the ribonucleotide chain.

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Cytokinins

Plant Hormnes Derived from Adenine

Cytokinins

 Contain adenine ring system with an attached 5-carbon _{Contain adenine ring system with an attached 5-carbon} hydrophobic group at the free NH

hydrophobic group at the free NH₂₂..

 Promote cell division in plants._{Promote cell division in plants.}

Zeatin Zeatin

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Nucleo

tides

Nucleosides with One or More Phosphates

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Common Ribonucleotides

IMP is the IMP is the bio-synthetic precursor synthetic precursor of nucleotides (AMP) of nucleotides (AMP)

Fig. 14.23a Fig. 14.23a

Note:

Note: Thymidine- Thymidine-5

5’’-monophosphate -monophosphate is not shown (not

is not shown (not

found in RNA

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Common Deoxy-Ribonucleotides

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Metabolic Functions of Nucleotides

(besides building blocks of nucleic acids)

Nucleotide Specific Functions:



ATP

–

phosphate acceptor/donor

GTP

–protein synthesis and signal

transduction



CTP

–

membrane & storage lipid

synthesis



UTP

–

carbohydrate synthesis &

degradation.

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The Central Role

of ATP in Energy Metabolism

Fig. 4.7 Fig. 4.7

Catabolism Catabolism

Anabolism Anabolism

Energy-Dependent

Processes:

 Biosynthetic processesBiosynthetic processes

 Active transport Active transport

 Mechanical work (muscles)_{Mechanical work (muscles)}

 Temperature regulationTemperature regulation

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A Closer Look at the Structure of

Adenylate Nucleotides (ATP)

High Energy Bonds

Group Leaving Potential

Energy (



G) of Hydrolysis

(



= easily broken) = easily broken)

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Energy of Hydrolysis

of Key Phosphorylated Biomolecules

Reaction



G (Kcal/mole)

AMP

AMP  Ade + P Ade + P_i_i

Glucose-6-phosphate Glucose-6-phosphate Fructose-6-phosphate Fructose-6-phosphate

ATP

ATP  ADP + P ADP + P_i_i ATP

ATP  AMP + P AMP + P_i_iPP_i_i ADP

ADP AMP + PAMP + P_i_i P

P_i_iPP_i_i  2 P 2 P_i_i

Phosphocreatine Phosphocreatine

Glycerate-Glycerate-11,3-bisphosphate,3-bisphosphate Carbamoyl phosphate

Carbamoyl phosphate Phosphoenolpyruvate Phosphoenolpyruvate

– – 1.51.5 – – 3.33.3 – – 3.83.8 – – 7.37.3 – – 7.67.6 – – 6.56.5 – – 8.08.0 –

– 10.310.3 –

– 11.811.8 –

– 12.312.3 –

– 14.814.8

(Modified from Table 4.1) (Modified from Table 4.1)

(Phosphocreatine) (Phosphocreatine)

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Significance of

“



G

”

“



G

”

Gibbs Free Energy

The energy difference before and The energy difference before and after a process or reaction occurs. after a process or reaction occurs.



G

°

= G

₂₂

– G

₁₁

If



G is

“

+

”

 Input of energy is required.Input of energy is required.  Reactions are Reactions are ““unfavorableunfavorable””..

If



G is

“

-

”

 Energy is given off.Energy is given off.

 Reactions are Reactions are ““favorablefavorable”” (or (or spontaneous).

spontaneous).

G

G₁₁ 

G

G₂₂ 

T ot al E ne rg y (G ) T ot al E ne rg y (G )  

Progress of Reaction

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Implications of



G

 Reactions with more negative _{Reactions with more negative}G give off more energy.G give off more energy.

 Energy given off (-_{Energy given off (-}G) can be used to do G) can be used to do ““workwork””..

 Reactions with large -_{Reactions with large -}G can be coupled to those with G can be coupled to those with +

+ G to promote unfavorable reactionsG to promote unfavorable reactions

Reaction



G (Kcal/mole)

Glucose-6-phosphate Glucose-6-phosphate ATP

ATP  ADP + P ADP + P_i_i

Phosphoenolpyruvate Phosphoenolpyruvate

– – 3.33.3 – – 7.37.3 –

– 14.814.8

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Cyclic Nucleotides

Second Messengers in Signal Cascades

Second Messenger

A short-lived intracellular chemical

signal molecule that relays a

message (stimulus) from an external

“

“first messengerfirst messenger””. This relay typically . This relay typically results in a cascade of events leading

results in a cascade of events leading

to a marked amplification of the first

messenger.

First Messengers:

First Messengers: Hormones, Hormones, neurotransmitters

neurotransmitters

Second Messengers:

Second Messengers: Ca Ca2+2+ ions, _ions,

inositol-Pi

inositol-Pi₃₃, diacylglycerol, , diacylglycerol, cyclic cyclic nucleotides

nucleotides..

Fig. 16.2 (An amplified enzyme cascade).

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How is cAMP formed?

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AMP---24

Cyclic AMP & Cyclic GMP

Second Messengers in Signal Cascades

Adenylate Cyclase

ATP → cAMP + PPi

 cAMP is involved in _{cAMP is involved in}manymany signal signal cascades.

cascades.

 hormone signaling (e.g. _{hormone signaling (e.g.}

adrenaline, glucagon), apoptosis, adrenaline, glucagon), apoptosis, disease reactions, neuron function. disease reactions, neuron function.

Guanylate Cyclase

GTP → cGMP + PPi

 cGMP is involved in nitric oxide _{cGMP is involved in nitric oxide} (NO) signaling.

(NO) signaling.

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cAMP-Mediated Signal Transduction

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Recap--Nucleotides

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

DNA Structure: Variations

on a Theme



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,

and due to low hydration



Z-DNA (zigzag

conformation) is

left-handed DNA that can form

as a result of torsion

during transcription

Figure 17.12 A-DNA, B-DNA, and Z-DNA

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Griffith Experiment



Transformation of

one strain by

another



Two strains of

bacteria



R—harmless (1)



S—deadly (2)



Heat killed S is also

‑

harmless (3)



Heat killed S makes R

‑

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Avery, MacLeod, and McCarty



Used the same assay system

–

Isolated compounds from Strain S

–

Added these to Strain R



Only DNA

transformed Strain R, ie, only isolated

DNA from strain S could make strain R harmful,

NOT PROTEINS.

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Hershey and Chase experiment

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Study Questions / Objectives

1.

1. Identify and/or describe the molecular components of nucleotides and Identify and/or describe the molecular components of nucleotides and nucleic acids, including distinctions between purines & pyrimidines, nucleic acids, including distinctions between purines & pyrimidines, nucleosides vs. nucleotides, DNA vs. RNA.

nucleosides vs. nucleotides, DNA vs. RNA. 2.

2. Exemplify & describe the occurrence and/or function of nitrogenous Exemplify & describe the occurrence and/or function of nitrogenous bases and related derivatives that are not part of nucleic acids.

bases and related derivatives that are not part of nucleic acids. 3.

3. Describe the role and relative energy yields of ATP and its derivatives Describe the role and relative energy yields of ATP and its derivatives (including other phosphorylated metabolites) in energy metabolism, and (including other phosphorylated metabolites) in energy metabolism, and the significance of

the significance of ““_G”G”.. 4.

4. Briefly describe the role or importance of cyclic nucleotides( cAMPand Briefly describe the role or importance of cyclic nucleotides( cAMPand cGMP) in cell signaling.

cGMP) in cell signaling. 5.

5. Describe how a phosphodiester bond is formed?Describe how a phosphodiester bond is formed? 6.

6. How does a DNA chain grow in the 5’-3’ direction?How does a DNA chain grow in the 5’-3’ direction? 7.

7. Describe Griffith, Avery/McLoed/Mccarthy, and Hershey& Chase’s Describe Griffith, Avery/McLoed/Mccarthy, and Hershey& Chase’s