Nucleotides

1. Chemistry of Nucleotides
Presented by: Wajeeha Akram
Department of Biochemistry and Molecular
Biology
NUMS

2. Outline:
Presentation covers the following aspects of Nucleotides:
 Discovery
 Composition
 Biochemical function
 Derivatives of Nucleotides & Significance
 Synthetic Nucleotides

3. Discovery
• In 1868, Friederich Miescher
isolated nucleic acid (then called
nuclein) from pus cells.
Friederich Miescher
(1844–1895)

4. Discovery
• Albrecht Kossel (Nobel prize,
1910) determined the chemical
composition of nucleic acid in 1882.
• In 1906, Kossel described the 4
bases in nucleic acids.
Albrecht Kossel
(1853–1927)

5. Composition of Nucleotides
• A nucleotide is made up of 3 components:
- a. Nitrogenous base (a purine or a pyrimidine)
- b. Pentose sugar, either ribose or deoxyribose
- c. Phosphate groups esterified to the sugar.

6. Composition of Nucleotides
• When a base combines with a pentose sugar, a nucleoside is formed.
• When the nucleoside is esterified to a phosphate group, it is called a
nucleotide or nucleoside monophosphate.

7. Composition of Nucleotides
• When a second phosphate gets esterified to the existing phosphate
group, a nucleoside diphosphate is generated.
• The attachment of a 3rd phosphate group results in the formation of
a nucleoside triphosphate.
• The nucleic acids (DNA and RNA) are polymers of nucleoside
monophosphates

8. Bases Present in the NucleicAcids
• Two types of nitrogenous bases;
- the purines and pyrimidines are present in nucleic acids.

9. Purine Bases
• The purine bases present in RNA and DNA are the same;
- adenine and guanine.
• Adenine is 6-amino purine and guanine is 2-amino, 6-oxopurine.
• The numbering of the purine ring with the structure of adenine and
guanine is as follow:

10. Purine Bases
6-amino purine 2-amino, 6-oxopurine

11. Minor Purine Bases
• These bases may be found in small amounts in nucleic acids and
hence called minor bases.
• These are hypoxanthine (6-oxopurine) and Xanthine(2, 6-di-
oxopurine).
Minor bases seen in nucleic acids

12. Minor Purine Bases
• Uric acid (2,6,8-tri-oxopurine) is formed as the end product of the
catabolism of other purine bases.
• It can exist in the "enol" as well as "keto" forms (tautomeric forms).
• Keto form is by far the predominant type under physiological
conditions

13. Pyrimidine Bases
• The pyrimidine bases present in nucleic acids are
 Cytosine
 Thymine and
 Uracil

14. Pyrimidine Bases
• Cytosine is present in both DNA and RNA.
2-Oxy,4-amino pyrimidine

15. Pyrimidine Bases
• Thymine is present in DNA and Uracil in RNA.
2,4-dioxy pyrimidine 2,4-dioxy-5-methyl pyrimidine

16. Modified pyrimidine bases
• A few other modified pyrimidine bases like dihydrouracil and 5-
methyl cytosine are also found rarely in some types of RNA.
Modified pyrimidine bases

17. Nucleosides
• Nucleosides are formed when bases are attached to the pentose
sugar, D-ribose or 2-deoxy-D-ribose.
Sugar groups in nucleic acids

18. Nucleosides
• All the bases are attached to the corresponding pentose sugar by a
beta-N-glycosidic bond between the 1st carbon of the pentose sugar
and N9 of a purine or N1 of a pyrimidine.
• The deoxy nucleosides are denoted by adding the prefix d- before the
nucleoside.

19. Nucleosides
• The carbon atoms of the pentose sugar are denoted by using a prime
number to avoid confusion with the carbon atoms of the purine or
pyrimidine ring.
• Atoms in sugar is denoted
with primed numbers.

20. Nucleosides
• Nucleosides with purine
bases have the suffix
• -sine, while pyrimidine
nucleosides end with
• -dine.

21. Nucleoside Triphosphates
• Corresponding nucleoside di- and tri- phosphates are formed by
esterification of further phosphate groups to the existing ones.
• In general, any nucleoside triphosphate is abbreviated as NTP or
d-NTP.

22. Nucleoside
Triphosphates

23. Nucleotides
• These are phosphate esters of nucleosides.
• Base plus pentose sugar plus phosphoric acid is a nucleotide.
• The esterification occurs at the 5th or 3rd hydroxyl group of the
pentose sugar.
• Most of the nucleoside phosphates involved in biological function are
5'-phosphates.

24.  The nucleic acids (DNA and RNA)
are polymers of nucleoside
monophosphates.
 The ester linkage is formed
between 5’PO of one nucleotide
and 3’OH of other nucleotide. This
formation is important as DNA and
RNA always read 5’ to 3’. Therefore
location of PO and OH tell us what
is an orientation of DNA.
Nucleotides

25. Biochemical Functions of Nucleotide
• Nucleotides are precursors of the nucleic acids, deoxyribonucleic acid
(DNA) and ribonucleic acid (RNA).
• The nucleic acids are concerned with the storage and transfer of
genetic information.
• Many metabolic pathways are regulated by the level of the
individual nucleotides (ATP, GTP, NADPH, NADH, AMP etc)

26. Biochemical Functions of Nucleotide
 The universal currency of energy, namely ATP,is a nucleotide
derivative.
 Nucleotides are also components of important co-enzymes like
 NAD+ and FAD, and
 metabolic regulators such as cAMP and cGMP.
 Nucleotides act as a second messenger in cell signaling.

27. Nucleoside Triphosphates
• 3', 5'-cyclic AMP or cAMP
is a major metabolic
regulator.
• Cyclic GMP also behaves
similarly.
• These are second
messengers in mediating
the action of several
hormones.
3',5'-cyclic AMP or cAMP

28. •High energy
compounds

29. 1- Adenine
ATP, ADP, AMP
 ATP is energy currency for cell
 ADP is part of many coenzyme
 ADP requires in oxidative phosphorylation and ETC
 cAMP is involved in cell signaling , glycogenolysisn, lipolysis
 Phosphoadenosine 5-Phoshosulfate (PAPs)-sulfate donor, acts as a coenzyme
in sulfotransferase reactions.
Derivatives Of Nucleotide And Their Functions

30. 2- Guanine
GDP, GTP, GMP
 GTP and GDP are high energy compound
 Involve in Citric acid cycle
 Protein Synthesis
 G-Proteins are part of cell membrane Receptor
 Cyclic GMP act as messenger for certain hormones
 GDP is carrier of activated sugar in biosynthesis of mucopolysaccharides
 Ribozyme action dependents on GMP

31. 3- Uracil
UDP
UDP-Glucose. Provide glucose for synthesis of glycogen, glycoproteins,
UDP-Glucuronic acid serves as a donor of glucuronide in conjugation
Reaction (formation of bilirubin)
4- Cytosine
CTP, CDP
CDP-choline serve as a donor of cholin for synthesis of phospholipids
CTP takes part in synthesis of lecithin
CDP takes part in synthesis of choline
Derivatives Of Nucleotide And Their Importance

32. Synthetic Nucleotide -Clinical Application
Chemotherapy
 5-fluoro- or 5-iodouracil
 6-thioguanine and 6-mercaptopurine
 5- or 6-azauridine
 5- or 6-azacytidine,
 8-azaguanine
 Cytarabine

33.  Methotrexate inhibits dihydrofolate reductase and use to treat
cancer, rheumatoid arthritis
 5-iodo-deoxyuridine inhibits Herpes keratitis
 Aminophyllin and theophyllin increase cAMP, bronchodilators
 Acyclovir inhibit viral infection
 Allopurinol, inhibits purine biosynthesis and xanthine oxidase
activity
 Suppress immunologic rejection during organ transplantation

34. Sources:
1. Harper’s Illustrated Biochemistry
2. Internet source
3. Dr. Asifa Majeed lecture