LEC 1

CH 460 Fundamentals of Biochemistry

Emphasis on: biological molecules
: structure, metabolism, chemistry
Objectives
: foundational knowledge
: preparation for specialization in Chemistry,
Biochemistry, health professions
: scientic thinking and communication

CH 115 Chapter 4

Syllabus

Grade breakdown

CH 115 Chapter 4

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CH 115 Chapter 4

Nucleic Acids (Ch. 4)

Nucleic acids derivatives of pyrimidine,

purine

CH 115 Chapter 4

Pyrimidines

The common pyrimidine bases in the tautomeric forms

predominant at pH 7.

Tautomeric forms of the bases

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CH 115 Chapter 4

The Chemical Differences Between DNA

and RNA Have Biological Significance
Why does DNA contain thymine?
Cytosine spontaneously deaminates to form
uracil
Repair enzymes recognize these "mutations" and
replace these Us with Cs
But how would the repair enzymes distinguish
natural U from mutant U?
Nature solves this dilemma by using thymine (5methyl-U) in place of uracil

The Chemical Differences Between DNA and

RNA Have Biological Significance

Deamination of cytosine forms uracil.

CH 115 Chapter 4

The Chemical Differences Between DNA

and RNA Have Biological Significance

The 5-methyl group on

thymine labels it as a
special kind of uracil.

Purines

The common purine bases in the tautomeric forms predominant

at pH 7.

CH 115 Chapter 4

Ribose and Deoxyribose

Note: numbers are primed on sugars but not bases

DNA & RNA Differences

Why is DNA 2'-deoxy and RNA is not?
Vicinal -OH groups (2' and 3') in RNA make it
more susceptible to hydrolysis
DNA, lacking 2'-OH, is more stable
This makes sense - the genetic material must be
more stable
RNA is designed to be used and then broken
down

CH 115 Chapter 4

Adenosine, a Nucleoside
(base + sugar)

Anti form

Carbohydrate stereochemistry
terminology

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CH 115 Chapter 4

Adenosine: Nucleoside with Physiological

Activity
Adenosine functions as an
autacoid, or local hormone
Influences blood vessel dilation,
muscle contraction,
neurotransmitter release, fat
metabolism
Adenosine is also a sleep
regulator. Adenosine rises during
wakefulness, promoting eventual
sleepiness.
Caffeine promotes wakefulness
by blocking binding of adenosine
to its neuronal receptors.

Nomenclature

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Bases, Nucleosides, Nucleotides

Base

nucleoside

5-nucleotide

A
G
Cytosine

cytidine

Uracil

uridine

cytidine 5-monophosphate or
CMP or 5-cytidylic acid
uridine 5-monophosphate or
UMP or 5-uridylic acid

ATP, a 5-Nucleotide
(base + sugar + phosphate)

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Nucleotide Functions
1. Provide energy for reactions:
ATP === > ADP + Pi
ATP === > AMP + PPi
2. High energy carrier molecules
UDP-glucose and CDP-diacylglycerol
3. Substrates for making DNA and RNA
All NTPs and dNTPs
4. Regulatory molecules
cAMP and cGMP
5. Coenzyme components
NAD+ and NADP+ ; FMN and FAD

Coenzyme
Nonprotein component of an enzyme
that provides a chemical functionality
not provided by the protein.
Often these are vitamins or contain
vitamins.

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The Nicotinamide Coenzymes NAD+/

NADH and NADP+/NADPH -carry out
hydride (H:-) transfer reactions. All
reactions involving these coenzymes
are two-electron transfers.

The cyclic nucleotide cAMP.

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cAMP functions
Signal the eects of hormones (adrenaline,
glucagon)
Activate protein kinases regulate glycogen and
lipid metabolism
Activate ion channels
Regulate cyclic nucleotide-binding proteins
Regulation of gene expression (prokaryotes)

Nucleoside 5'-Triphosphates Are

Carriers of Chemical Energy
Nucleoside 5'-triphosphates are indispensable
agents in metabolism because their phosphoric
anhydride bonds are a source of chemical
energy
Bases serve as recognition units
Cyclic nucleotides are signal molecules and
regulators of cellular metabolism
ATP is central to energy metabolism
GTP drives protein synthesis
CTP drives lipid synthesis
UTP drives carbohydrate metabolism

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ATP contains two pyrophosphate linkages.

The hydrolysis of phosphoric acid anhydrides
is highly favorable.

Phosphoric Acid Anhydrides

ADP and ATP are examples of phosphoric acid
anhydrides
Note the similarity to acyl anhydrides
Large negative free energy change on
hydrolysis is due to:
electrostatic repulsion
stabilization of products by ionization and
resonance
entropy factors
solvation

CH 115 Chapter 4

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Hydrolysis of Phosphoric Anhydrides is

Highly Favorable

Electrostatic repulsion and resonance in acetic anhydride

Hydrolysis of ATP to ADP

(and hydrolysis of ADP to
AMP) relieves electrostatic
repulsion.

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Why are certain compounds energy

rich?
Resonance
stabilization of
phosphate ion product
Charge repulsion in
reactants
Tautomerization and/or
solvation of products
Entropy contribution

High-energy Carrier Molecules

CH 115 Chapter 4

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Chemical
structures of
ribonucleic
acid (RNA)
and deoxyribonucleic
acid (DNA)

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DNA Synthesis by Polymerase

CH 115 Chapter 4

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Shorthand Notations for DNA

pApGpTpApC

or

1'

AGTAC

3'

or

a
P

5'

OH

5-AGTAC-3

Deoxyribose is the vertical line. The anomeric C is 1 and

phosphodiester bonds link the sugars 3-5.
a and b are cleavage sites for nucleases.
Write chains 5 to 3 left to right

What are the

shorthand
notations for this
sequence?

CH 115 Chapter 4

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Alkaline hydrolysis of RNA proceeds through a

cyclic intermediate not possible in DNA

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Chargaffs Rules

CH 115 Chapter 4

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