2023-2024

Fundamentals
of
Biochemistry
BCHE 2030
Nucleotides and
Nucleic Acids
Prof Kwok Fai LAU
School of Life Sciences
CUHK
Nucleotides
Nucleotides have a variety roles in cellular metabolism

Constituents of nucleic acids

Energy currency

Chemical links in the response of cells to hormones and

extracellular stimuli

Enzyme cofactors

2
Structure of nucleotides

nitrogen containing base

Nucleoside
pentose Nucleotide
phosphate

Conformations of ribose

3
Pentose
Ribose 5-phosphate is synthesized from the pentose
phosphate pathway

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Nitrogenous bases
General Structure Common base Uncommon base

N6-methyladenine

4 thiouracil

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Origin of the ring atoms of purines
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Synthesis of deoxyribonucleotides

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Nucleic acids are polymers of nucleotides

Nucleotides are joined by

phosphodiester bonds

Base

Base

The backbones of both DNA and RNA

are hydrophilic
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Polymerases can catalyze the formation of phosphodiester bonds

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DNA forms a double helix

James Watson, Francis Crick and Maurice Wilkins

were awarded the 1962 Nobel Prize for Physiology
or Medicine, "for their discoveries concerning the
molecular structure of nucleic acids and its
significance for information transfer in living
material".
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The Watson-Crick model of DNA has the following major features
(1) Two polynucleotide chains wind around a common axis to
form a double helix
(2) The two strands of DNA are antiparallel
(3) The surface of the double helix contains two grooves of
unequal width: the major and minor grooves

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(4) Each base is hydrogen bonded
to a base in the opposite strand
to form a planar base pair.

An adenine pairs with a thymine;

a guanine pairs with a cytosine
> complementary base pairing

(5) The bases are nearly

perpendicular to helix axis

Figure 4.13
Biochemistry 6th Ed Figure 3-8 13
©2007 WH Freeman Principles of Biochemistry 3rd Ed
©2008 Wiley
DNA supercoiling
DNA double helices can fold up on
themselves to form structures created by
supercoiling
Supercoiled DNA molecules are more complex
Most DNA molecules inside cells are subject
to supercoiling

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DNA molecule in chromosome is highly coiled > can be
compressed into a relatively small space
E. coil chromosome
6
bp
Mx2 M

If all the DNA in a human are unraveled

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bp
Biochemistry. The molecular basis of life, 3rd Ed
©2003 McGraw-Hill

https://slate.com/technology/2014/05/close-encounter-what-if-the- 15
moon-orbited-much-closer-to-earth.html
RNA
RNA molecules differ from DNA in the following ways
(1) The pentose sugar in RNA is ribose instead of
deoxyribose in DNA
(2) Substitution of uracil for thymine in RNA i.e. Bases in
RNA are A, U, G, C
(3) RNA exists as single strand

Cells contain several kinds prominent of RNA: messenger

RNA (mRNA); transfer RNA (tRNA); ribosomal RNA (rRNA)

Eukaryotic cells contain additional small RNA molecules.

e.g. small nuclear RNA (snRNA); micro RNA (miRNA); small
interfering RNA (siRNA)
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Many RNAs have more complex 3-D structure. e.g. Base
pairing occurs intramolecularly, giving rise to stem-loop
structures

Figure 3-9
Principles of Biochemistry 3rd Ed
©2008 Wiley

Transfer RNA

Figure 17.22b 17
Biochemistry. The molecular basis of life, 3rd Ed
©2003 McGraw-Hill
Some non-Watson-Crick base pairings occur in RNA molecules
e.g. 3-D structure of phenylalanine tRNA of yeast

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Double helical DNA (and RNA) can
undergo denaturation and renaturation

Melting temperature (tm) = the temperature

at the midpoint of the transition
tm depends on
pH
Ionic strength
The size of the DNA
The base composition of the DNA 19
(high CG > high tm)
Overview of nucleic acid functions

Figure 3-12; 3-13; 3-14

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Principles of Biochemistry 3rd Ed
©2008 Wiley
DNA carries genetic information

Figure 10.1
Human Genetics: Concepts and Applications 7 th Ed
©2007 McGraw Hill

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Ribozymes

Thomas R. Cech Sidney Altman

The Nobel Prize in Chemistry 1989 was awarded to Thomas R. Cech and
Sidney Altman "for their discovery of catalytic properties of RNA
Mutations
Alteration in DNA structure that produce permanent changes
in genetic information therein
(1) Spontaneous mutations
e.g. Tautomerism A base is changed by the repositioning of
a hydrogen atom
T - A amino
Tautomerism

T - A imino
DNA replication

T - A C - A imino
DNA replication

C - A imino
C - G
An A-T pair is replaced by G-C base pair
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e.g. Deamination Hydrolysis changes a normal base to an
atypical base containing a keto group in place of the original
amine group

G - C

A - U

A - T

An G-C pair is replaced by A-T base pair

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(2) Induced mutations

e.g. Alkylating agents dimethyl sulfate

Methylguanine pairs with

thymine instead of cytosine
G - C

O6-Methyl G - T

A - T

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 e.g. DNA intercalating agents Benzopyrene (the major
mutagen in tobacco smoke)
insert into DNA
adjacent base pairs are either deleted or new base
pairs are inserted > frame-shift mutation

Insertion Normal Deletion

DNA

mRNA
tRNAs

protein

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e.g. Radiation - ultraviolet radiation
Induces formation of pyrimidine dimers on the same DNA
strand

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Block transcription
Other functions of Nucleotides
(1) Energy carriers in cells
Hydrolysis of nucleoside triphosphate provides
chemical energy to drive many cellular reactions

Adenosine triphosphate (ATP) is most widely used in cells

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Hydrolysis of ATP

Hydrolysis +

ATP ADP

Hydrolysis +

ADP AMP

Hydrolysis of each phospho-anhydride bond yields about 30kJ/mol

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(2) Coenzymes
complex organic
molecules that are
required for the functions
of enzymes

Many conenzymes
contain adenine
nucleotides

can function as transient

carriers of specific
functional groups, or
involve in redox reactions
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e.g. Nicotinamide adenine dinucleotide (NAD+)

NAD+ is a coenzyme in many redox reactions

nicotinamide ring acts as an electron carrier

NAD+ (oxidized) NADH (reduced)

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(3) Regulatory nucleotides
Cells respond to their environment by taking cues from hormones or
other external chemical signals
Hormones or other external chemical signals interact with cell surface
receptors often leads to the production of second messengers
Many second messengers are nucleotides e.g. cyclic AMP, cyclic GMP
and ppGpp (guanosine tetraphosphate)

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