Cell and Molecular Biology Module

1. Dr Zahid Azeem
BIOCHEMISTRY
AJK Medical College, Muzaffarabad
MBBS2019- CMB Module

2. Early discovery
Early discovery of DNA in 1953 and subsequent
elucidation of how DNA directs synthesis of RNA,
which directs assembly of protein– the co called
central dogma were monumental achievements
marking early days of molecular biology.

3. Central Dogma of Molecular Biology

4. Nucleic Acid
Two type of chemically similar nucleic acids
a.Deoxyribonucleic acid (DNA) and
b.ribonucleic acid (RNA)
are principle information carrying molecules of the cell

5. Two types of Molecules

6. Nucleic Acid
Deoxyribonucleic acid contains all the information
required to build the cells and the tissues of an
organism.
The exact replication of this information in any
species assures its genetic continuity from generation
to generation and is critical to the normal
development of an individual.

7. Nucleic Acid Monomers
The Monomers from which DNA and RNAs are built
are called nucleotides. Purines are fused ring
structure while pyrimidines contain single ring
structure

8. Purine bases of plants
 Plants contain certain methylated purines.
 Caffeine (1,3,7-trimethylxanthine):
 It is found in coffee.
 It acts as a stimulant.
 Theophylline (1,3-dimethylxanthine):
 Present in tea leaves.
 It acts as a bronchial smooth muscle relaxant.
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9. Minor (unusual) pyrimidines found in nucleic acids
Methylcytosine present in DNA & dihydrouracil
present in tRNA.
Pyrimidine analogs:
These have structural similarities to pyrimidines.
They act either as inhibitors of enzymes in the
metabolism of pyrimidines or interact with nucleic
acids.
5-fluorouracil:
It inhibits the enzyme thymidylate synthase.
It is used in the treatment of cancer.
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10. Minor/Unusual bases
• Specific DNA and RNA contains small quantities
of Minor/modified bases also.
• These modifications includes-
• Methylation
• Hydroxymethylation
• Glycosylation
• Alteration of atoms.

11. • Modification of Adenine:
N-methyladenine,
N6N6- dimethyladenine
• Modification of Guanine:
7-methylguanine
• Modification of Cytosine:
5-methylcytosine
5-hydroxymethylcytosine
Minor/Unusual base

12. • Modification of Uracil:
Dihydroxyuracil
• Special Bases:
Hypoxanthine (6-oxopurine)
Xanthine (2,6-dioxopurine)
Uric acid (2,6,8-trioxopurine)

13. Special Bases
Uric Acid (2,6,8-trioxypurine)

14. Commonality of monomers
All the nucleotides have common structure;
phosphate group linked by phosphodiester bond to
the pentose (a five carbon sugar molecule) that in
turn linked to nitrogen and carbon containing ring
called base;

15. Bases
A. The bases are often abbreviated by A, T, C, G and U.
These same single letter abbreviation are commonly
used to denote the entire nucleotide in nucleic acid
polymer. Both DNA and RNA contains three
common bases A, C, G. However, T is only DNA
specific and U is present only in RNA.
B. In nucleotides carbon 1’ of sugar is attached with N9
of base in purine, however, In case of pyrimidine N1
of base is attached with carbon 1’ of sugar.

16. Nucleosides
Cell and extracellular fluids contain small
concentration of nucleosides, combination of base
and sugar without phosphate.

17. Composition of nucleic acids
Nucleic acids
Polymer of
Nucleotides
PhosphateNucleosides
Bases
Purines
Pyrimidines
Sugar
Ribose
deoxyribose

18. Nucleoside
18
OH-CH2
SUGAR
1’
2
’
3’
4’
5
’

21. NUCLEIC ACID
Linear Polymer with End-to-End Directionality
Like polypeptide nucleic acid strand has an end to end
chemical orientation.
5’ end (FIVE PRIME END) has Phosphate group on the
5’ carbon of its terminal sugar.
This directionality, plus the fact that synthesis proceeds
from 5’ to 3’ direction give rise to the convention
that polynucleotide sequences are written and read
in
5’  3’ direction.

22. End to End directionality with phosphodiester bond

23. Linear sequence of nucleotide linked by
phosphodiester bond constitutes to primary structure
of nucleic acids.
Like polypeptides, polynucleotides can twist and fold
into three dimensional conformations stabilized by
covalent bonds.
Only primary structure of DNA and RNA are
generally similar

25. Native DNA
Double helix of complementary anti-parallel
strands
James D Watson and Francis H.C crick proposed that
DNA has double helical structure.
DNA consists of consists of two associated polynuctide
chains wind together to form a double helix.
Two sugar-phosphate backbones are on the outside of
the double helix and the bases projects to the interior.
Orientation of two strands anti-parallel, that is, their
5’3’ are opposite

26. Antiparallel pairing

27.  Hydrophilic
deoxyribose-phosphate
 Hydrophobic bases
stacked inside
 Overall structure
resembles a twisted
ladder
 Results Major and
Minor groove formation
 Dactinomycin D
intercalates narrow
groove

28. Bases Complementarity
This base complementarity is consequence of the
size, shape and chemical composition of the bases.
The presence of such thousands of hydrogen bonds in
the DNA molecule contribute greatly to the stability
of double helix.
In 1950 a Scientist Chargaff revealed composition of
bases. He said A and always equal to T and similar C
& G are equal.

29. Watson and crick base pairing

30. Why DNA is twisted around axis of Symmetry
The double helix of DNA is like a twisted ladder.
In this ladder curving side shows sugar and phosphate
backbone
While
Rungs are base pairs. Spaces between base pairs is 3.32
Å (Angstorm) or 0.332nm. After addition of 10 bases
DNA completes one twist with total space of 3.32nm.
Such consecutive twists result into Major and minor
grooves.

32.  Two chain coiled
against axis of
symmetry.
Base are
perpendicular to axis
PDB is parralel

37. The end