Nucleic Acids
Nafisa Rawshan(MSc, B.Pharm)
Lecturer
Department of Pharmacy, Primeasia University
Original slides: Ms. Rubaba Karim (Asst. Professor)
Types of nucleic acids
There are two main types of nucleic acids:
DNA (deoxyribonucleic acid)
It is the reserve bank of genetic information that exclusively maintain the
identity of different species and also regulate cellular functions. DNA controls
protein synthesis through mediating RNA.
RNA (ribonucleic acid)
This performs several functions carried out by different types of RNA-
mRNA specifies the sequence of amino acids in protein synthesis. rRNA is
associated with structure and function of ribosome. tRNA delivers amino acids
to ribosomes for protein synthesis.
Other functions-
• It serves as a carrier for genetic information.
• This forms links between mRNA and amino acids being coupled in protein
synthesis.
• RNA is an essential component of ribosomes and some enzymes.
Nucleotides
Nucleic acids (both DNA and RNA) are the polymers of
nucleoside monophosphates. Nucleotides are essentially
consist of a nitrogenous base, a pentose sugar and a
phosphate.
Pentose sugar
A five carbon sugar in a pentose ring form; ribose sugar
(RNA nucleotide or ribonucleotide) and deoxyribose sugar
(DNA nucleotide or deoxyribonucleotide).
Nitrogenous base
The bases are aromatic heterocyclic compounds that are attached to
nucleic acids are of two structural type; purine and pyrimidine
where purine consists of linked 5 and 6- membered rings while
pyrimidine consists of 6- membered rings.
Purines
There are 2 purines commonly found in both DNA and RNA which are
adenine (A) and guanine (G).
Pyrimidine
There are 3 pyrimidines; cytosine (C), thymine (T) and uracil (U).
Cytosine can be found in both DNA and RNA whereas Thymine is
found only in DNA and Uracil is found only in RNA.
U T C
A G
The phosphates
Nucleotide contains phosphate group which is a strong acid
and gives nucleic acids their acidic nature. This could be
attached through the ―OH group at the 5 or 3 carbon
position of the sugar unit.
The anionic properties of nucleotide due to the negative
charges contributed by the phosphate group.
A nucleoside could be di- or tri-phosphate according
to the number of phosphate group present. Eg. A
nucleoside with adenine base with 3 phosphate is termed
adenosine triphosphate (ATP) while that with 2
phosphate groups and 1 phosphate group are termed
adenosine diphosphate (ADP) and monophosphate
(AMP) respectively.
Adenosine 5’- Thymidine 5’-
monophosphate monophosphate
Nucleoside monophosphate AMP, GMP,
CMP, TMP, UMP
Nuceloside di-phosphate ADP, GDP,
CDP, TDP, UDP
Nicleoside tri-phosphate ATP, GTP, CTP,
Polynucleotides
The pentose sugars are bound to nitrogenous bases by
β-N-glycosidic bonds.
Covalent bonding between N9 of purine ring to C1 of pentose
sugar while N1 of pyrimidine to C1 of a pentose. The 5 end
of a sugar always joined through a phosphate
molecule to the 3 end of the adjacent sugar.
The primary polymeric structure
Nucleotides are linked together by phosphodiester bonds
between ―OH group at 3C of pentose sugar on one nucleotide
with the ―OH group at 5C of the sugar of corresponding
nucleotide through a phosphate molecule.
The sugar-phosphate linkage forms the symmetrical backbone
to which variable bases are attached that determines the
coding of nucleic acids and identify their types (DNA or RNA).
Structure of DNA
DNA is a polymer of deoxyribonucleotide.
The double helical DNA:
o DNA is right handed double helix consisting of two strands of
polydeoxyribonucleotide chains where the strands are antiparallel; ie. where one
strand runs fro 5 to 3 direction where the adjacent strand from 3 to 5 direction.
o The deoxyribose
phosphate backbone is
hydrophilic and stands
outside the structure
while the hydrophobic
bases are stacked
inside.
Watson-Crick model of
DNA helix
Complementary base pairing
The two strands are held together by complementary bases through
formation of hydrogen bonding. That means a purine base of one
strand will make pair with the adjacent pyrimidine base of the
other strand through H-bond. Guanine will only pair up with
cytosine while adenine will only pair up with thymine (in case of RNA,
adenine will pair up with uracil).
Dimensions
One of the 2 strands is known as the template or sense strand that
encodes genetic information while the opposite strand is known as
antisense strand.
Along the backbone, there is a wide major grooves and narrow minor
grooves.
It is through these grooves many drugs and proteins can make contact
with the bases of DNA without requiring the helix to open.
Nucleoprotein
Organization of DNA in the cell
In prokaryotic cells DNA is loosely packed while in eukaryotic cells
DNA is found in association with protein called histone to form
nucloesomes which are nucleoproteins.
These nucleosomes further coil up the DNA within the
chromosomes, hence forming the basic structure of chromosome.
There are different types of histone protein that are catagorized on the
basis of the ratio of lysine and arginine residues within their structure.
Histones are basic in nature so strongly bind to the acidic DNA.
Linker
DNA
Separation of DNA strands in the double helix
Denaturation
The separation of double helix or unwinding of DNA can be
done by increasing temperature, exposure to
radiation (uv or x-ray) or treatment with alkali due to
hydrolysis of H-bond that holds the strands.
Renaturation
Denaturation is reversible.
The denatured DNA, that is the two separated DNA
strands can be reformed into a double helix under
suitable condition (by adjusting the temperature
and pH conditions).
Under such condition the H-bonds between the
bases of the two complementary DNA strands are
reformed, thereby returning to its helical form. This
is called renaturation or reannealing.
DNA replication
Initiation
Certain proteins recognize and bind to this origin of replication.
The proteins facilitate the enzyme helicase to unwind and separate
the DNA helix into single-stranded DNA. As the DNA opens up, Y-
shaped structures called replication forks are formed.
Elongation
During elongation, an enzyme called DNA polymerase adds
DNA nucleotides to the 3' end of the newly synthesized
polynucleotide strand.
Only the nucleotide complementary to the template
nucleotide at that position is added to the new strand.
Termination
Termination requires that the progress of the DNA
replication fork must stop or be blocked.
Termination occurs at a specific locus and involves the
interaction between two components: (1) a
termination site sequence in the DNA, and (2) a protein
which binds to this sequence to physically stop DNA
replication.
RNA Structure
RNA is a single stranded polymeric chain of ribonucleotides which are
held together by 3’,5’-phosphodiester bond.
The bond is between 3’-hydroxyl on the sugar of one ribonucleotide
through a phosphate to the 5’-hydroxyl on the sugar of another
ribonucleotide.
The sugar-phosphate linkage form a symmetrical backbone
like the DNA and the variable bases stick out from the backbone.
o The single strand of RNA may fold at certain places to give a
double stranded structure (similar to DNA) if the
complementary base pairs are in close proximity.
o Such RNA is known as A-form double helix where the two
strands are anti-parallel. In such case, RNA forms a stem
loop structure.
o In RNA, adenine pairs with uracil through two H-bonds
while guanine pairs with cytosine through three H-
bonds.
Codons and anti-codons
mRNA makes up 3-5% of RNA in a cell. These molecules are
single helical strands with several thousands of nucleotides
in which triplets of bases act as codons during the
synthesis of protein within the ribosomes.
tRNA makes up 10-15% of RNA content within the cell. There
are 75-90 nucleotides that are present in the single
stranded tRNA molecule that wound into a double helix
forming three prominent bulges.
Translati
on
The genetic code (is the
sequence of nitrogenous
bases in RNA.
