Introduction to nucleic acids, nucleosides, nucleotides

1. Dr. Ifat Ara Begum
Associate Professor
Dept of Biochemistry
Dhaka Medical College
Introduction to nucleic acid,
Chemistry of nucleotides

2. Nucleic
Acid

3. Introduction
Biopolymers, or large biomolecules
Are essential to all known forms
of life
The most important of all
biomolecules
synonymous with polynucleotide
They were named for their initial
discovery within the nucleus, and for the
presence of phosphate groups (related to
phosphoric acid).

4. Contd
Although first discovered within
the nucleus of eukaryotic cells, nucleic
acids are now known to be found in all life
forms including
within bacteria, archaea, mitochondria, ch
loroplasts, viruses, and viroids

5. Contd
In all living things, nucleic acids
function to
 Create
and
 Encode
and then
 Store information
in the nucleus of every living cell of
every life-form organism on Earth.

6. Contd
In turn, they transmit and express that
information inside and outside the cell
nucleus to
 The interior operations of the cell
 Ultimately to the next generation of each
living organism.

7. Definition
Nucleic acid may be defined as
the polymer of nucleotides
connected by
3’-5’ phosphodiester bond

8. Components
Components are similar to its monomer
(nucleotide):
1. A pentose (5-carbon) sugar: Ribose /
deoxy ribose
2. Phosphate (phosphoric acid)
3. Nitrogen base: purine / Pyrimidine bases

9. Two types of nucleic acid
1. DNA:
 Polymer of deoxyribonucleotide / d-
ribonucleotide
 d-ribonucleotide = deoxy ribose
sugar + phosphate + nitrogen base

10. Contd
2. RNA:
 Polymer of ribonucleotide
 Ribonucleotide = Ribose sugar +
phosphate + nitrogen base

11. Contd
If phosphate is removed from the
structure of nucleotide, the
remaining structure is called
nucleoside

15. Nucleoti
de

16. Definition
The monomer/building block of nucleic
acid
In other words, phosphorylated
nucleoside
Occurs in mono/di/tri phosphate forms

17. Structure

18. Components
Have three components:
1. A pentose (5-carbon) sugar: Ribose /
deoxy ribose
2. Phosphate (phosphoric acid)
3. Nitrogen base: purine / Pyrimidine bases

19. Contd
 Phosphate remains attached with 5th
carbon of pentose sugar
 Nitrogen base remains attached with 1st
carbon of pentose sugar

20. Contd
 If the sugar is ribose , the nucleotide is
termed as ribonucleotide
 If the sugar is deoxyribose (d-ribose), the
nucleotide is termed as
deoxyribonucleotide (d-ribonucleotide)

21. 1. Ribose & deoxyribose
Ribose is a pentose sugar with aldehyde
function
Deoxyribose (d-ribose) is the ribose
sugar with oxygen atom removed
from its 2nd
carbon

23. Contd
 To avoid confusion between the numerals
of various atoms of nitrogen base &
ribose sugar, the carbons of ribose sugar
is designated by numerals with a prime
 Example: 1’, 2’, 3’, 4’, 5’

24. 2. Phosphate
Total number of phosphate in a
nucleotide may be 1 or 2 or 3
Nucleotides of mono phosphate
variety (AMP, GMP etc) can be
converted to their corresponding
diphosphate variety (ADP, GDP etc)
& triphosphate variety (ATP, GTP
etc) by subsequent phosphorylation

26. 3. Nitrogen base
Two types:
A. Purine base
B. Pyrimidine base

27. Purine base
Adenine (A), Guanine (G), Xanthine,
Hypoxanthine, Uric acid etc.
They contain purine nucleus which is an
aromatic heterocyclic 9 atom ring
composed with 4 nitrogen & 5
carbons

28. Contd
Raw materials for synthesis of
purine nucleus are:
 Aspartic acid (Asp), Glutamine
(Gln), Glycine (Gly)
 CO2
 Formyl tetrahydrofolate (F-FH4) &
methenyl tetrahydrofolate (M-FH4)

30. Contd
Purine bases are derivatives of
purine nucleus
For synthesis of purine nucleotides
all the previously /above mentioned
raw materials plus ribose 5 – P are
needed

31. Pyrimidine base
Cytosine (C), Uracil (U), Thymine
(T), Orotic acid .
They contain pyrimidine nucleus which is
an aromatic heterocyclic 6 atom
ring composed with 2 nitrogen & 4
carbons

32. Contd
Raw materials for synthesis of
pyrimidine nucleus are:
 Aspartic acid (Asp)
 Glutamine (Gln)
 CO2

34. Contd
Pyrimidine bases are derivatives of
pyrimidine nucleus
For synthesis of pyrimidine
nucleotides all the previously
/above mentioned raw materials
plus ribose 5 – P & methylene
tetrahydrofolate are needed

35. Contd
Remember,
 A, G, C contain NH2 group
 T contains CH3 group
 Among the all nitrogen bases, only
five bases are found in nucleic acid :
A, G, C, U, T
 T is found only in DNA , U only in
RNA
 The other three (A, G, C) are found
both in DNA & RNA

37. Point Purine bases Pyrimidine bases
Structure Derivatives of aromatic
heterocyclic 9 atom
(4N, 5C) ring compound
Derivatives of
aromatic
heterocyclic 6
atom (2N, 4C) ring
compound
Raw
material
for
synthesis
Asp, Gln, Gly, F-FH4,
M-FH4, CO2
Asp, Gln, CO2
Types A, G C, T
In DNA Both C, T
In RNA Both C, U

39. Nomenclature of nucleotides
N. Base Nucleoside (N.
Base + Sugar)
Nucleotide
(nucleoside +
phosphate) with
examples
Purine bases
Adenine
(A)
Adenosine,
d-adenosine
AMP (adenylic acid),
dAMP
Guanine
(G)
Guanosine, d-
guanosine
GMP (guanylic acid),
dGMP

40. Contd
N. Base Nucleoside (N.
Base + Sugar)
Nucleotide
(nucleoside +
phosphate) &
examples
Pyrimidine bases
Cytosine
(C)
Cytidine, d - cytidine CMP (cytidylic acid),
dCMP
Uracil
(U)
Uridine UMP (uridylic acid)
Thymine
(T)
D - thymidine dTMP (thymidylic
acid)

41. Contd
Nucleoside:
 Derivative of purine/pyrimidine base and
composed of ribose/d-ribose sugar
attached with the nitrogen base
If ribose : Ribonucleoside
If d-ribose: deoxy ribonucleoside (d-
ribonucleoside)

42. Function of nucleotides
1. Monomer of nucleic acid
&
thus conveys genetic information
2. Participate in energy metabolism
&
serve as energy store : ATP, GTP etc

43. Contd
3. Regulatory function as
physiological mediator:
 Acts as intracellular 2nd
messenger:
cAMP, cGMP
 Helps in signal transduction : G-
Protein (made of GTP)
 Causes platelet aggregation : ADP
 Regulation of coronary blood flow:
Adenosine

44. Contd
4. Acts as:
 Coenzymes: e.g. NAD, FMN, FAD etc
 Allosteric effector to regulate
enzyme activity: e.g. ATP, AMP,
ADP etc
 Carrier of active intermediates in
synthetic processes : e.g. UDP
glucose for glycogen synthesis
 Methyl donor

45. Nucleotide biosynthesis
Two pathways for biosynthesis of
nucleotides:
1.De-novo synthesis: Nucleotides are
synthesized new from simple precursor
molecules. Occurs primarily in liver
(cytoplasm)
2.Salvage pathway: Recycling of the
nitrogen bases. Occurs primarily in
extrahepatic tissues.

48. 1. De-Novo
synthesis

49. 1)Ribonucleotide de-novo synthesis
A) Purine nucleotides:
The purine ring is synthesized first from
amino acids, tetrahydrofolate derivatives &
CO2
Then ribose phosphate is added from
PRPP (phospho ribosyl pyrophosphate) to
form a purine nucleotide.

50. Contd
IMP (inosine monophosphate) is the 1st
purine nucleotide product of the
biosynthetic pathway.
IMP is the precursor of AMP and GMP
Feedback inhibition controls both the
overall rate of purine biosynthesis and the
balance between AMP and GMP
production.

53. Contd
A) Pyrimidine nucleotides:
The pyrimidine ring is synthesized first
Then ribose phosphate is added from
PRPP (phospho ribosyl pyrophosphate) to
form a pyrimidine nucleotide.

55. 2. d-ribonucleotide de-novo
synthesis
As sugar moiety of PRPP is ribose & as
PRPP provides this ribose sugar during
nucleotide synthesis, ribonucleotide
(purine/pyrimidine) are the end products of
nucleotide synthesis.
But as DNA uses d-ribonucleotide , cells
require pathway to convert ribonucleotide
into their deoxy forms.

56. Contd
This conversion is done by direct
reduction of ribose sugar by ribonucleotide
reductase ,
which involves removal of oxygen from 2nd
carbon of ribose
This reduction of ribonucleotides to d-
ribonucleotides occurs only in diphosphate
form.

59. 2. Salvage
pathway

60. Introduction
A salvage pathway is a pathway in
which
nucleotides (purine & pyrimidine) are
synthesized
from intermediates in the degradative
pathway for nucleotides / nucleic acids.

62. Contd
Salvage pathways are used to
recover bases and nucleosides that are
formed
during degradation of RNA and DNA
The salvaged bases and nucleosides
can then be converted back into
nucleotides.
.

63. Contd
.
Points Purine Pyrimidine
Salvaged
bases
Adenine,
Hypoxanthine,
Guanine
Uracil , Thymine
Enzymes
involved
HGPRT Uridine phosphorylase
, Uridine kinase ,
Thymidine
phosphorylase,
Thymidine kinase
Products IMP, GMP UMP, dTMP

64. Contd
Salvage pathway is important in some
organs because some tissues cannot
undergo de novo synthesis
.

65. Salvage pathway for Purine
nucleotides
.
Points Description
What happens? Recycling the products of
nucleic acid breakdown
Where happens? Primarily in extrahepatic
tissues
What does the pathway
use?
Free bases ( A, G)
Which enzymes are
responsible for recycling?
APRT & HGPRT (HPRT)

66. Contd
Most purine bases are recycled rather than
degraded
Points Description
How effective is the
pathway?
90% of daily purine
nucleotide biosynthesis
occurs
Why this pathway occurs? Salvage pathway needs
less energy than de-
novo biosynthesis

69. Contd
HGPRT :
 Catalyzes the salvage synthesis of IMP
and GMP from the purine bases
hypoxanthine and guanine respectively,
utilizing PRPP as a co-substrate
 Its defect results in the accumulation of its
substrates, hypoxanthine and guanine,
which are converted into uric acid by
means of xanthine oxidase

70. Contd
APRT :
 Catalyzes the salvage synthesis of
adenosine monophosphate (AMP) from
adenine utilizing PRPP as a co-substrate.
 Elevated APRT activity may contribute to
purine overproduction.

71. Salvage pathway for Pyrimidine
nucleotides
Recyclation of free pyrimidine bases

72. Contd

73. Salvage pathway versus de-novo
synthesis of nucleotides
Salvage pathway De-novo synthesis
Provides most of the
required nucleotides in
non-dividing or slowly
dividing cells
It is important in rapidly
proliferating cells
Much less energy
consuming process
Very expensive energy
wise, only done when
absolutely necessary

74. Catabolism
of
nucleotides

76. Catabolism of purine nucleotide
.

77. Contd
Abnormalities with purine catabolism
leads to hyperuricemia & gout
Which can be treated by
drugs inhibiting xanthine oxidase

78. Catabolism of pyrimidine nucleotide
.

79. Contd
Pyrimidine nucleotide degradation is just
reverse of their synthesis
Pyrimidine ring can be degraded (unlike
purine rings which can not be cleaved in
human cells)

80. Contd
End product of catabolism :
 CO2, NH3, acetyl CoA (from beta
alanine) , succinyl CoA (from beta
aminoisobutyrate)
 Highly water soluble
 Have no clinical significance