BASIC PRINCIPLES OF
MEDICINE 1:
FOUNDATIONS TO MEDICINE
Structure and Function
Nucleic Acids
Part 1 – Nucleosides, Nucleotides
and the Phosphodiester Bond
Transcription Translation
Replication DNA RNA Protein
Reverse transcription
The “Central Dogma” of Molecular Biology
•Describes the flow of information from the heredity material
(typically dsDNA to protein) via an RNA intermediate
•Both DNA and RNA are nucleic acid polymers
•In most organisms the hereditary material is double stranded
DNA (dsDNA)
•In some viruses RNA (via reverse transcription) or single
stranded DNA (ssDNA) is the hereditary material
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Monomeric Units
Each nucleotide contains three components:
1) A nitrogenous heterocyclic base
-purine or pyrimidine
2) A pentose sugar
-ribose (RNA) or deoxyribose (DNA)
3) A phosphoric acid group in ester linkage to the 5’ carbon of the
pentose
O Heterocyclic Base
Phosphate ester N
N
H
O-
O 5’
P O
O- N N NH2
O
1’
The phosphate is esterified HO OH
to the C5 of the pentose sugar Pentose sugar In both DNA & RNA the base is
by means of an ester bond (in this diagram, ribose is shown) attached to the 1 position of the
sugar through a β-N-glycosidic
bond
The Nucleotide unit 3
Structures of deoxyribose and ribose, and of the
nitrogenous bases in DNA and RNA
Purines are heterocyclic
compounds consisting of a
pyrimidine fused to a 5
member imidazole ring.
>adenine and guanine
Pyrimidines are heterocyclic
compounds containing
nitrogen atoms at position 1
and 3 of a 6 member ring.
>cytosine, thymine (DNA), and
uracil (RNA) DNA contains A,G,C & T
RNA contains A,G,C & U
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Ribose and Deoxyribose:
•A pentose sugar is composed of
five carbon atoms
•RIBOSE (found in RNA): hydroxyl
(-OH) group attached to the 2’-
carbon
•DEOXYRIBOSE (found in DNA):
the hydroxyl (-OH) group attached
to the 2’-carbon is replaced by a
hydrogen (-H) group
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Chemical structures of
DNA and RNA
Nucleosides consist of a
nitrogenous base and a ribose or
deoxyribose sugar.
Nucleotides consist of a nitrogenous base, a
ribose or deoxyribose sugar, and a
phosphate group. The base is attached to
the 1’ carbon of the sugar by a β-N-
glycosidic bond attached to nitrogen
number one of pyrimidine and number 9 of
the purine.
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Functions of Nucleoside Triphosphates:
1. Precursors of the nucleotides for
RNA and DNA synthesis.
2. ATP - universal chemical energy
3. GTP - protein synthesis
4. UTP - biosynthesis of glycoproteins
5. CTP - phospholipid biosynthesis
6. Formation of coenzymes
Nomenclature clarification: nucleotides are more accurately termed nucleoside
mono, di or tri phosphates depending on the number of phosphates attached to
the sugar.
*** Nucleoside Triphosphates are required for synthesis of DNA and RNA
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polymers.
DNA and RNA are
nucleic acid
polymers.
DNA/RNA polymerase
catalyzes the formation
of a phosphodiester
bond between the 3’
OH group of the
deoxyribose/ribose on
the last nucleotide and
the 5’-phosphate of the
dNTP/NTP precursor.
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Phosphodiester bonds - catalysed by DNA & RNA Polymerase.
The 3’ OH gp of one residue DNA illustrated in the diagram
becomes linked to the 5’ CH2 gp
of the next. D 5’ terminus D
O N N
O
O P O
A A
O P O
O
T O
5 CH T
2
Base Base E 5 CH
E
O
DNA/RNA
2
Base Base
M O
M
4 1
2
P Polymerase 4 1
P
3
L 3 2
L
OH H
A O H
A
O O O
T O P O
T
E
O–P–O–P–O P O + 2 Pi O E
O O O 5
CH2
S O
Base Base S
5
CH2
Base Base T 4 1 T
O
R 3 2 R
4 1
A OH A
3 2 H
N N
N.b., always uses a
OH H
D 3’ terminus D
dNTP/NTP precursor
The directionality of this bond means that polynucleotides have one end that terminates in a 5’
phosphate & the opposite end terminating in a 3’ OH. Cleavage of the triphosphate is the energy source
for this reaction.
Phosphodiester bonds - formed by DNA Ligase
Responsible for sealing nicks in DNA during replication and repair
O
O
O P O
O P O 5’ terminus
O
O
5 CH CH2
2
Base O
Base
O
4 1
3 2 Ligase 3
O H
OH H
+ H2O
Condensation O P O
reaction O
Phosphodiester
O 5 CH2 Bond
O Base
O P O
O
5
CH2 OH H
O
Base
4 1 3’ terminus
N.b., always uses a
3 2
dNMP/NMP
OH H
ATP is the energy source for this reaction
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