Biologically important nucleotides Nucleic acids · Biologically important nucleotides Nucleic...

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Biologically important nucleotides Nucleic acids for students of General Medicine Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University Medical Faculty Ďuračková Zdeňka

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Page 1: Biologically important nucleotides Nucleic acids · Biologically important nucleotides Nucleic acids for students of General Medicine Department of Medical Chemistry, Biochemistry

Biologically important nucleotides

Nucleic acids

for students of General Medicine

Department of Medical Chemistry, Biochemistry and Clinical Biochemistry,

Comenius University

Medical Faculty

Ďuračková Zdeňka

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NUCLEOPROTEINS

PROTEIN NUCLEIC ACID

(protamins, histons) (polynucleotide)

mononucleotide

ribo/deoxyribo-

nuclease

Phosphoric acidnucleoside

Purine and

Pyrimidine bases

Saccharide

mononucleotidase

(phosphatase)

nucleosidase

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Tautomeric forms (uracil)

N

N

OH

OH N

N

OH

O N

N

O

O

HH

H

N

N

OH

OH N

N

N

N

HH

H

OH

lactim lactam

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Nucleoside Nucleotide

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-N-glycosidic bond

NUCLEOSIDES

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13deoxy

guanine

deoxyguanosine

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Nucleotides

• supply for NA synthesis

• biologicaly active nucleotides

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AMP

ADP

ATP

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The function of polyphosphates in

the organism

ATP - universal energetic metabolism

GTP - metabolism of proteins, proteosynthesis

CTP – metabolism of lipids

UTP – metabolism of saccharides

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regulation:

• synthesis of peptide hormons

• immunological processes

• lactation

• secretion of stomach juice

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P

+

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25NAD+ + 2H NADH + H+

H H

H+ + e H+ + e

H-

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Co-operation of

NAD+

with FAD, FMN

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H-

H+FAD + 2H FADH2

FMN

alloxazin

ribitol

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ThioethanolaminePanthotenic acid

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NUCLEIC ACID

DNA (deoxyribonucleic acid)

RNA (ribonucleic acid)

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pentose

pentose

pentose

pentose

base

base

base

base

P

5´- end

3´- end

P

P

P

PSequence of nucleotides

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Linear chain of polynucleotide (example with RNA)

3´, 5´ phosphodiester bond

5´ end → 3´ end

N

N

N

N

NH2

O

OH

CH2OP

O

O

O

_

_

NH2

N

N

O

O

OH

O

P O

O

O

_

CH2

O

5´-end

3´- endP

A

C

OH

OH

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deoxyribose adenine thymine deoxyribose

deoxyribose thymine adenine deoxyribose

deoxyribose guanine cytosine deoxyribose

deoxyribose cytosine guanine deoxyribose

deoxyribose thymine adenine deoxyribose

P

P

P

P

P

P

P

P

P P

Complementary chains5’-end

3’-end

3’-end

5’-end

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DNA

G

A

T

C

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Chargaff’s rules

• DNA isolated from different animal species contains the

same bases (A, G, C, T)

• The relative proportion of individual bases is species

dependent

• The base abundance of individual species’ DNA is

independent of age, diet, gender, or environmental changes

• A/T = G/C = 1 A + G = T + C

A + T / G + C = 1,3 – 1,5 at higher animal species

USA 1905 - 2002

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Structure of DNA

2 April 1953

MOLECULAR STRUCTURE OF NUCLEIC ACIDS

A Structure for Deoxyribose Nucleic Acid

J. D. WATSON, F. H. C. CRICK

NATURE,VOL 171, page 737, 1953

Nobel price 1962

American geneticist

1928 -

English

biophysicist

1916 - 2004

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Mutual possition of purine and pyrimidine bases

in double helix of DNA

Mutual possition of bases and ribose

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Double helix

of DNA

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B-DNA A-DNA Z-DNA

The possition

of bases

Base pairs

per turn

Helix

Perpendicular

10

Right-handed

Skewed

11

Right-handed

Zik-zak

skewed

12

Left-

handed

Different kinds of DNA

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Interactions in DNA

Histons +

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Melting point

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Superhelix

DNA

Histones

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H1

(H2A, H2B, H3, H4)2

Nucleosomes

Like white

pearls necklace

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H1

(H2A, H2B, H3, H4)2

Nucleosomes

Like white pearls

necklace

A necklace curls

better around the

neck

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Arrangement

of DNA in the

nucleus

DNA

DNA+His

Superhelix

Chromatin

Chromosome

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NUCLEIC ACIDS

DNA (deoxyribonucleic acid)

RNA (ribonucleic acid)

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Minorit basis and

nucleotides

in RNA

Uracil Pseudouridine

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Pseudouridine - Ψ

Pseudouridine is biosynthesized from uridine via the action of Ψ

synthases.

- Ψ’s role in local structure stabilization

- Ψ - regulators of viral latency processes in human immunodeficiency

virus (HIV) infections

- Mutation of Ψ – increasing of t-RNA instability

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RNA

Phosphoribosyl chain

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Why DNA is more stabile than RNA?

1. DNA consists of Thymine whereas RNA consists of Uracil (in place

of Thymine).

Thymine in DNA confers to more stability

2. Additional -OH (hydroxyl) group at the 2′ position in RNA makes it

more reactive

4. RNA is easily degradable. With this fact, we can infer that it cannot

support longer life spans

3. Furthermore, RNA undergoes mutations at a faster rate as compared

to DNA

RNA is less stable than DNA

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Why DNA is more stabile than RNA?

1. DNA consists of Thymine whereas RNA consists of Uracil (in place of Thymine).

Thymine in DNA confers to more stability.

2. Additional -OH (hydroxyl) group at the 2′ position in RNA makes it more reactive.

4. RNA is easily degradable. With this fact, we can infer that it cannot support longer

life spans.

3. Furthermore, RNA undergoes mutations at a faster rate as compared to DNA.

RNA is less stable than DNA.

Thymine Uracil

deoxyribose ribose

splitting of the bond

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Ribonucleic acids

• Mediator RNA (m-RNA) – simple linear chain

Transfer of genetic information from DNA to ribosoms

Codon – three nucleotides – one AA

• Ribosomal RNA (r-RNA) – complex with acidic proteins

Matrix for proteosynthesis

• Transfer RNA (t-RNA) – clover leaf

Transfer of AA to ribosoms

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DNA

hnRNA polyAAAA

IntronsExons

mRNA

m-RNA

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r-RNA

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Ribosome of eukaryotic

cell

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t - RNA

CCA –AA-binding site3’-end

5’-end

Anticodon

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CO

C

NH2

R

N

N

NH2

P

O

O-

N

N

CH2

O OH

OO

PO

O

O-

CH2

O OH

OO

Bonding of AA to 3´-end of t-RNA

Cyt

t-RNA

3´- end of t-RNA

Ester bond between

-COOH of AA and

-OH group of ribose

Amino acid

A

C

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DNA unfolding prior to transcription

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Codon - anticodon

complementarity

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Ala

Codon - anticodon

complementarity

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Ala

Codon - anticodon

complementarity

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Ending of

translation

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Oxidative effect of nitrous acid HNO2

A - T I - C

G - Cchange of nitrogen base pairing

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Effect of hydroxylamine

C - G Hydroxy-C =>

change of nitrogen base pairing A - T

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Nucleotide transcription in DNA 1 page

Nucleotide transcription in DNA of E. coli

1 book (800 pages)

Nucleotide transcription in human DNA

800 books

1977 – Primary structure of bacteriophage

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Length of all DNA in human

• 1,2.1010 base pairs – 4 m long chain in 46 chromosomes of one cell

• Number of cells in the organisms = 1013

• Length of DNA in the organisms of all cells = 4.1010 km

• Distance from the Earth to the Sun = 1,5 . 108 km

• The length of all DNA in human is 100x longer than the

distance from the Earth to the Sun

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„ Just like a girl taking off

her clothes,

the naked truth has the same properties,

- both are achievable “

Robert Jeffers

Jan Klein: motto of the book

„ Molecular basis of heredity“ (in Slovak), 1964