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1. Chemistry of Nucleic acids

2. Nucleic acids
Nucleic acids are repositories and transmitters of
genetic information
Nucleic acids are the polymers of nucleotides i.e.
they are built up by the monomeric units - nucleotide
Nucleic acids are of two types namely
deoxyrihonucleic acid (DNA) and ribonucleic acid
(RNA).

3. Structure of Nucleotides
Nucleotides essentially consists of
Nucleobase, sugar and phosphate.
The term nucleoside refers to base + sugar.
Thus,
Nucleotide is nucleoside + phosphate

6. Structure and function of DNA
DNA is a polymer of deoxyribonucleotides (or
simply deoxynucleotides
The monomericd eoxvnucleotidesin DNA are hefd
together by 3',5'-phosphodiesterb ridges

8. DNA double Helix
The double helical structure of DNA was proposed
by lames Watson and Francis Crick in 1953
(Nobel Prize, 1962)
The structure of DNA double helix is comparable to
a twisted ladder

12. Salient features of Watson-Crick model of DNA
(now known as B-DNA)
1 . The DNA is a right handed double helix. It consists of two
polydeoxyribonucleotide chains (strands) twisted around
each other on a common axis.
2. The two strands are antiparallel, i.e., one strand runs in the
5' to 3' direction while the other in 3' to 5’ direction.
3. The width (or diameter) of a double helix is 20 Ao (2 nm).
4. Each turn (pitch) of the helix is 34 Ao(3.4 nm) with 10 pairs
of nucleotides, each pair placed at a distance of about 3.4 Ao

13. 5. Each strand of DNA has a hydrophilic deoxyribosep
hosphate backbone (3'-5' phosphodiester bonds) on the
outside (periphery)o f the molecule while the hydrophobic
bases are stacked inside (core).
6. The two polynucleotide chains are not identical but
complementary to each other due to base pairing
7. The two strands are held together by hydrogen bonds
formed by complementary base pairs. The A-T pair has 2
hydrogen bonds while G-C pair has 3 hydrogen bonds.
The G = C is stronger by about 50% than A=T.

14. 8. The hydrogen bonds are formed between a purine and a
pyrimidine only. The only base arrangement possible in DNA
structure, from spatialc onsiderationsis A-T, T-A, G-C and C-
C.
9. The complementary base pairing in DNA helix proves
Chargaffs rule. The content of adenine equals to that of
thymine (A = T) and guanine equals to that of cytosine (G =
C).
10. The genetic information resides on one of the two strands
known as template strand or sense strand. The opposite
strand is antisense strand. The double helix has (wide) major
grooves and (narrow) minor grooves along the
phosphodiester backbone. Proteins interact with DNA at
these grooves, without disrupting the base pairs and double
helix.

15. Functions of DNA
DNA is the reserve bank of genetic information
,ultimately responsible for the chemical basis of life
and heredity.

16. DNA is organized into genes, the fundamental units
of genetic information. Genes control protein
biosynthesis through the mediation of RNA.

18. Structure of RNA
RNA is a polymer of ribonucleotides held together by 3',5'-
phosphodiester bridges.
Although RNA has certain similarities with DNA structure,
they have specific differences

19. l. Pentose : The sugar in RNA is ribose in contrast to
deoxyribose in DNA.
2. Pyrimidine : RNA contains the pyrimidine uracil in place of
thymine (in DNA).
3. Single strand : RNA is usually a single stranded
polynucleotide. However, this strand may fold at certain
places to give a double stranded structure, if complementary
base pairs are in close proximity
4. Chargaff's rule-not obeyed : Due to the single-stranded
nature, there is no specific relation between purine and
pyrimidine contents. Thus the guanine content is not equal
to cytosine (as is the case in DNA).

20. 5. Susceptibility to alkali hydrolysis : Alkali can hydrolyse
RNA to 2',3'-cyclic diesters. This is possible due to the
presence of a hydroxyl group at 2' position. DNA cannot be
subjected to alkali hydrolysis due to lack of this group.
6. Orcinol colour reaction : RNAs can be histologically
identified by orcinol colour reaction due to the presence of
ribose

21. Types of RNA
Messenger RNA (mRNA) : 5-10%
Transfer RNA (tRNA) : 10-200%
Ribosomal RNA (rRNA) : 50-80%
 Heterogeneous nuclear RNA (hnRNA)
 Small nuclear RNA (snRNA)
 Small nucleolar RNA (snoRNA) and
Small cytoplasmic RNA (scRNA)

23. Clover leaf model of tRNA

24. Clover leaf model of tRNA contains four arms, each
arm with a base paired stem
1. The acceptor arm : This arm is capped with a sequence
CCA (5' to 3'). The amino acid is attached to the acceptor arm.
2. The anticodon arm : This arm, with the three specific
nucleotide bases (anticodon), is responsible for the
recognition of triplet codon of mRNA. The codon and
anticodon are complementary to each other.

25. 3. The D arm : It is so named due to the presence of
dihydrouridine.
4. The T C arm : This arm contains a sequence of T,
pseudouridine (represented by psi, ) and C.
5. The variable arm : This arm is the most variable in tRNA.
Based on this variabiliy.
Base pairs in tRNA :
The acceptor arm - 7 bp
The T C arm - 5 bp
The anticodon arm - 5 bp
The D arm -4bp

30. BIOSYNTHESIS OF
PURINE RIBONUCLEOTIDES

31. The purines are built upon a
pre-existing ribose 5-phosphate

38. SALWAGE PATHWAY FOR PURINES

40. DEGRADATION OF PURINE
NUCLEOTIDES

42. DISORDERS OF PURINE
METABOLISM

43. 1. Hyperuricemia and gout
Normal Conc. of serum uric acid: 3-7 mg/dl.
[In women, it is slightly lower (by about 1 mg) than in men]
Daily excretion of uric acid in humans is about 500-700 mg
Hyperuricemia refers to an elevation in the serum
uric acid concentration

44. Gout is a metabolic disease associated with
overproduction of uric acid
Sodium urate.
ln severe hyperuricemia, crystals of sodium urate get deposited in
the soft tissues, particularly in the joints.
Tophi
This causes inflammat ioni n the joints resultingi n a painful gouty
arthritis
Sodium urate and/or uric acid may also precipitate in kidneys and
ureters that results in renal damage and stone formation.

45. Gout is of two types-primary and secondary
Primary gout : lt is an inborn error of metabolism due to
overproduction of uric acid
Secondary gout : Secondary hyperuricemia is due to
various diseases causing increased synthesis or
decreased excretion of uric acid

48. TREATMENT OF GOUT
Allopurinol
This is a structural analog of hypoxanthine that
competitively inhibits the enzyme xanthine oxidase.
Allopurinol is oxidized to alloxanthine by xanthine
oxidase.
Alloxanthine, in turn, is a more effective inhibitor of
xanthine oxidase. This type of inhibition is referred to as
suicide inhibition

50. Pseudo Gout
This disorder is caused by the
deposition of calcium pyrophosphate
crystals in joints.
Where as, serum uric acid
concentration is normal in pseudo gout

51. Lesch-Nyhan syndrome
This disorder is due to the deficiency of hypoxanthine-
guanine phosphoribosyl transferase (HGPRT)
An enzyme of purine salvage pathway
It is a sex linked metabolic disorder since the structural
gene for HGPRT is located on the X-chromosome.
It affects only the males and is characterized by
excessive uric acid production.

52. Imunodeficiency disorders associated with
purine metabolosm
The deficiency of adenosine deaminase (ADA) causes
severe combined immunodeficiency (SCID) involving T-
cell and usually B-cell dysfunction.
ADA deficiency results in the accumulation of dATP
which is an inhibitor of ribonucleotide reductase and,
therefore, DNA synthesis and cell replication.
The deficiency of purine nucleotide phosphorylase is
associated with impairment of T-cell function

53. BIOSYNTHESIS OF PYRIMIDINE
RIBONUCLEOTIDES

58. Basic information about DNA

59. Central dogma of life

60. Cell cycle

61. Replication is a process in which DNA
copies itself to produce identical daughter
molecules of DNA

62. Replication is semi-conservative

63. Natlve DNA
Formation of replication bubble and fork
RNA primer
DNA helicases
Single-stranded DNA binding (SSB) protein
DNA polymerase lll
DNA polymerase I
DNA ligase

74. INHIBITORS OF DNA REPLICATION
Bacterial Topo isomerase (Gyrase) inhibitors: antibiotics
such as ciprofloxacin, novobiocin and nalidixic acid.
These are widely used as antibacterial agentssince they
can effectively block the replication of DNA and
multiplication of cells.
Human topoisomerase inhibitors : Anticancer agents
such as adriamycin, etoposide, doxorubicin.
The nucleotide analogs that inhibit DNA replication:
6-mercaptopurnie , 5-fluoro uracil .

75. TRANSCRIPTION

76. Transcription is a process in which
ribonucleic acid (RNA) is synthesized
from DNA

77. 1. Initiation
2. Elongation
3. Termination
Stages of transcription

78. Overview of transcription

79. Promoter Region

81. Base pairing relationship

82. RNA Polymerase

93. Promoter Region

94. Eukaryotic transcription

96. Outline of post-transcriptional modification

102. Schematic of a mature mRNA

103. GENETIC CODE
The three nucleotide (triplet) base
sequences in mRNA that act as code words
for amino acids in protein constitute the
genetic code or simply codons

104. The codons are composed of the four
nucleotide bases
These four bases produce 64 different
combinations (43)
UAA, UAG and UCA are stop
codons/termination codons
AUG and GUG are Initiation codons

105. Characteristics of genetic code
Universal
Specific
 Non-overlapping and
Degenerate

108. Wobble hypothesis

109. It is the phenomenon in which a single
tRNA can recognize more than one
codon. This is due to the fact that the
third base (3'-base) in the codon often
fails to recognize the specific
complementary base in the anti-codon
(5'-base)