Chemistry of nucleotides
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Chemistry of Nucleotides
Part – 1V.S.RAVI KIRAN
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V.S.RAVIKIRAN, MSc., Department of Biochemistry,
ASRAM Medical college, Eluru-534005.AP, [email protected]
om
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Chapter at a Glance• The reader will be able to answer questions on the following topics:
• Purines and pyrimidines
• Nucleosides and nucleotides
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Discovery
• In 1868, Friederich Miescher
isolated nucleic acid (then called
nuclein) from pus cells.
FriederichMiescher
1844–1895
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Discovery
• Albrecht Kossel (Nobel prize,
1910) differentiated RNA and
DNA in 1882.
• In 1906, Kossel described the 4
bases in nucleic acids.Albrecht Kossel
NP 19101853–1927
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Functions
• 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.
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Functions
• 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.
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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.
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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.
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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
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Bases Present in the Nucleic Acids
• Two types of nitrogenous bases;
- the purines and pyrimidines are present in nucleic acids.
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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 are shown in Figure.
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Purine Bases
Adenine is 6-amino purine 2-amino, 6-oxopurine
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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
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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.
Minor bases seen in nucleic acids
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Pyrimidine Bases
• The pyrimidine bases present in nucleic acids are
cytosine,
thymine and
uracil.
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Pyrimidine Bases
• Cytosine is present in both DNA and RNA. Structures are shown in
Figure.
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Pyrimidine Bases
• Thymine is present in DNA and uracil in RNA. Structures are shown in
Figure.
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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
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Nucleosides• Nucleosides are formed when bases are attached to the pentose
sugar, D-ribose or 2-deoxy-D-ribose.
Sugar groups in nucleic acids
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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.
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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.
Numbering in base and sugar groups. Atoms in sugar is denoted with primed numbers.
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Nucleosides• The names of the
different
nucleosides are
given in Table.
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Nucleosides
• Nucleosides with purine bases have the suffix -sine, while pyrimidine
nucleosides end with -dine. vi. Uracil combines with ribose only; and
thymine with deoxy ribose only.
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Nucleosides
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Nucleotides
• These are phosphate esters of nucleosides.
• Base plus pentose sugar plus phosphoric acid is a nucleotide.
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Nucleotides
• 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.
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Nucleosides
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Nucleotides
• Since 5'-nucleotides are more often seen, they are simply written
without any prefix.
• For example, 5'-AMP is abbreviated as AMP; but 3' variety is always
written as 3'-AMP.
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Nucleotides
• Moreover, a base can combine with either ribose or deoxy ribose,
which in turn can be phosphorylated at 3' or 5' positions.
• One purine and one pyrimidine derivative are given as examples in
Table 43.3.
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Nucleotides
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Nucleotides
• Many co-enzymes are derivatives of adenosine monophosphate.
• Examples are NAD+, NADP, FAD and Co-enzyme A.
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Nucleotides
• Nucleotides and nucleic acids absorb light at a wavelength of 260 nm;
this aspect is used to quantitate them.
• As nucleic acids absorb ultraviolet light, chemical modifications are
produced leading to mutation and carcinogenesis.
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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.
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Nucleoside Triphospha
tes
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Nucleoside Triphosphates
• Nucleoside diphosphate
contains one high energy
bond and triphosphates
have 2 high energy bonds.
• ATP is the universal energy
currency.
Adenosine triphosphate (ATP)
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Nucleoside Triphosphates
• It is formed during oxidative processes by trapping the released
energy in the high energy phosphate bond.
• A phosphodiester linkage may be formed between the 3' and 5'
positions of ribose group. Such compounds are called cyclic
nucleotides.
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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
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Nucleoside Triphosphates
• Deoxy ribonucleotides are used for synthesis of DNA and
ribonucleotides for RNA.
• In pseudouridylic acid (found in tRNA) uridine is attached to ribose
phosphate in a C-C bond instead of C-N bond in UMP.
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Nucleoside Triphosphates
Different attachment of uracil to sugars
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Nucleoside Triphosphates
• High energy compounds are listed in Table. 20.2.
• Please note that active methionine, amino acid adenylates, active
sulfate, etc. are higher energy compounds containing adenosine
monophosphate.
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• High energy compounds are listed in Table.
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High energy compounds are listed in Table.
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