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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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NUCLEOPROTEINS
PROTEIN NUCLEIC ACID
(protamins, histons) (polynucleotide)
mononucleotide
ribo/deoxyribo-
nuclease
Phosphoric acidnucleoside
Purine and
Pyrimidine bases
Saccharide
mononucleotidase
(phosphatase)
nucleosidase
3
4
7
8
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
9
10
11
Nucleoside Nucleotide
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-N-glycosidic bond
NUCLEOSIDES
13deoxy
guanine
deoxyguanosine
14
15
16
17
18
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
+
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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31
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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
5´
3´
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
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Right-handed
Skewed
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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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50
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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
„ 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