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Chemical Structures of Nucleic Acids and Lipids

Department of Biochemistry

Jeerus Sucharitakul
Nucleotides
Important chemicals in cellar metabolism
2) Energy currency in living organisms: ATP and GTP
3) Intracellular response of hormone and stimuli from
extracellular signaling: cAMP
3) Genetic information in living organisms

Three components of nucleotides


-Nitrogenous bases
-Pentose (ribose, C5)
-Phosphate
Nitrogenous Bases
Two types of nitrogenous bases

-Both DNA and RNA contain purine bases and cytosine of


pyrimidine bases but thymine is only for DNA and uracil is
only for RNA.
Pentoses
-Nucleic acids have two kinds of pentoses.
-2′-deoxy-D-ribose in deoxyribonucleotides (DNA)
-D-ribose in ribonucleotides (RNA)
-N-9 of purines and N-1 of pyrimidines are joined with pentoses
at 1′carbon of pentose (N-β-glycosyl linkage)
-Phosphate is esterified at 5 carbon by o-glycosidic bond.
Nucleotides and Nucleic Acid Nomenclature

Base + Pentose = Nucleoside


Base + Pentose + Phosphate
= Nucleotide

Nucleoside
Pentose and Bases Components in DNA and RNA

DNA RNA
Polynucleotides (DNA and RNA)
-Nucleotide units are joined
forming DNA and RNA by
5′-phostphate covalently
linked to 3′-hydroxy group
of the next nucleotide.
-Backbones are an alternating
of phosphates and pentoses.
-The phosphate groups are
ionized with negatively charge.
-the end of 5 carbon and 3
carbon lacking nucleotide are
called 5′ end and 3′ end.
-The direction of nucleic acids
always represented as from
5′ end to 3′ end.
Chemical Properties of Phosphodierter Bonds
-Backbone is very slowly hydrolyzed in nonenzymatic reaction,
and can be accelerated by enzyme nuclease.
-RNA is rapidly hydrolyzed under alkaline condition whereas
DNA is degraded in acidic condition.
Chemical Properties of Nitrogenous Bases
-Purines and pyrimidines are weakly basic compounds.
-Both type are aromatic and highly conjugated resulting in
resonance stabilization.
-The resonance properties result in partial double-bond
character: pyrimidine rings are planar and purine rings are
nearly planar.

O OH OH

HN N N

O O HO
N N N
H H H

Resonance forms of pyrimidine (Uracil)


Chemical Properties of Nitrogenous Bases
Purines and pyrimidines are hydrophobic and exist in neutral
form at physiological pH.

Hydrophobic bases are


stacked similar to a stack of
coins with interaction by
van der Waals and dipole-
dipole force. These forces
are the most important to
stabilized nucleic acid
structure.
Chemical Properties of Nitrogenous Bases
Complementary base pairs
-Carbonyl and amino substitute groups on purine and
pyrimidine bases are important to interaction between nucleic
acid molecules via hydrogen bond.
Complementary base pairs

James Watson Francis Crick

-Hydrogen bonds can allow association


of two, three and four strands of
nucleic acids.
-In 1953, Watson and Crick defined the
two types of base pairs A-T (or U) and
G-C, called base pairs.
-Specific base pairs permits the fidelity
of heritages of the genetic information.
Three Dimensional Structure of Nucleic Acids

-In 1950, Rosalin Frankin and


Maurice Wilkins used x-ray
diffraction to analyze DNA
chains as a helical structure.
-Watson and Click proposed
the structure that consists of
two helical DNA chains
wound around the same axis
with right-handed double
helix.
DNA Double Helix Structure

-Right–handed double helix


-The hydrophilic backbones
expose to polar environment.
-The hydrophobic aromatic
bases of both strands are
stacked inside the double
helix perpendicular to the
long axis.
-The geometry in base pairing
creates a major and minor
groove.
Major and Minor Groove in DNA Structure
More hydrophobic environment
Base exposure site Base exposure site
Major groove Major groove

Minor groove Minor groove


Backbone exposure site Backbone exposure site

More hydrophilic environment


The Variation of Three Dimensional Structure of
Nucleic Acids
-The deviations from Watson-Crick DNA structure can be found
in cellular DNA but the key properties is still not affected,
base complementarity and antiparallel strand.
-The variation of structures are caused by different conformation
of three things
1. Different conformation of deoxyribose
2. The free rotation of C′-1-N-glycosyl bond
3. The rotation of phosphodeoxyribose backbone

Different conformation of pentose


The Variation of Three Dimensional Structure of
Nucleic Acids
The free rotation of C′-1-N-glycosyl bond

-Purines are restricted in two stable forms, syn and anti


conformation.
-Pyrimidines are restricted in to anti conformation because of
steric hindrances between sugar ring and carbonyl oxygen.
The Variation of Three Dimensional Structure of
Nucleic Acids
B form DNA is referred to Watson-crick model.

A form DNA:
-Right-handed double helix
-Dehydrated form: the most compact form
-Structure of DNA tending to crystallize

Z form DNA:
-Left-handed double helix
-Zigzag appearance in sugar-phosphate backbone
-Purine bases is are syn conformation, alternating with
pyrimidine in anti conformation: the extended form
-Evidenced some structures in living organism, both
prokaryotes and eukaryotes
The Variation of Three Dimensional Structure of
Nucleic Acids
Unusual DNA Structures

Duplex structures
Hairpin or cruciform structure
-Palindrome sequence;
identical reading either
forward or backward (inverted
repeats)
-Self-complementary within
each strand
Unusual DNA Structures
Three- or four-DNA strand structures
-They are important structure to DNA metabolism, repilcation,
recombination and transcription.
Triplex DNA (C≡G•C+ or T=A•T)

Protonated cytidine

Hoogsteen pairing
Unusual DNA Structures

Quadruplex DNA (G tetraplex)

-High rich sequence of G


-Highly stable
-Possible two directions
Lipids
Lipids (Greek: lipos = fat) are biological substances soluble in
organic solvent.
Lipid classification
Storage lipid
-Fatty acids -Fats and oils are energy storage
-Triacylglycerols form in living organism.
-Glycerophospholipids -Hydrocarbon derivatives are very
-Sphingolipids low oxidation state.
-Cholesterol -Hydrophobic molecule with low
water solvation different from
polysaccharides and polypeptides.
-Organisms can store energy without
carrying a lot of mass weight.
Fatty Acids

-Fatty acids are carboxylic acids with long carbon chain ranging
from 4-36 carbon atoms.
-The hydrocarbon chains can be fully saturated or unsaturated
with double bonds.
-Notation of fatty acids
C1 is referred to carboxyl carbon
C18 with saturated hydrocarbon chain, 18:0
C20 with two double bonds between C9-C10 and between C12-
C13, 20:2(∆9,12)
-The double bonds of polyunsaturated fatty acid are not
conjugated, (no −CH=CH−CH=CH− but −CH=CH−CH2−CH=CH−).
-All natural fatty acids are synthesized as cis conformation.
-Trans conformation can be occurred in dairy animals because of
the fermentation in rumen of them.
Physical Properties of Natural Fatty Acids
-By length of chains
-By degree of unsaturation
Physical Properties of Natural Fatty Acids

•Most fatty acids have an


even number of C because
biosynthesis is carried out
by adding C2 units of acetyl
-CoA.
•The first double bond of an
unsaturated fatty acid
commonly occurs between
C9 and C10.
Triacylglycerols
-Triacylglycerols are fatty acids ester of glycerol.
-They are composed of one glycerol molecule with the same
(simple) or different kind (mixed) of fatty acids linked by
esterification.
-Triacylglycerols are nonpolar molecules, insoluble in water.
-Most of eukaryotes store energy as form of triacylglycerol
(oil droplets) in separated phase in specialized cells,
adipocytes (animals)
and plants (germinating seeds).
-Adipocyte and germinating seeds
have enzyme lipase, enzymes
that catalyze hydrolysis of ester
bond to release fatty acids from
triacylglycerols.
Biological Waxes
•Biological waxes are esters of long chain fatty acids (14-36)
with long chain of alcohols.
•Waxes function as water-repellent substances and coating
material in skins.
•Pharmacoceutical, cosmetic and chemical industries
Lanolin from wood
Beeswas
Extract from spermaceti (from whales)
Structural Lipids in Membranes
Structural Lipids in Membranes
-Membrane are lipid bilayer composed of amphipathic
molecules: outer is hydrophilic and inner is hydrophobic.
Glycerophospholipids (Phosphoglycerides)
-Fatty acid components link to C1 and C2 of glycerol via ester
bonds.
-The highly charged group of phosphate links to C3 of glycerol.
Glycerophospholipids

•Glycerol 3-phosphate is esterified at C1 and C2.


•Amphipathic molecules
Glycerophospholipids
Phospholipids with Ether-Linked Fatty Acids
Some animal tissues and
unicellular organism can
synthesize ether phospholipid
with two fatty acid chain linked
to glycerol 3-phosphate by
ether bonds.
Plasmalogen: about 50% of
heart vertebrate tissue
phospholipids are plamalogen,
and it can be found in bacteria
and invertebrates
Platelet-activating factor:
substances are released by
leukocytes to stimulate platelets

aggregation and the release


of serotonin resultng in
Glycolipid
-Membrane lipids
contain a simple sugar
or complex
oligosaccharides.
-Predominate
membrane lipid types
are found n plant cells
Galactolipid
-One or two galactose
residues connected to
C3 of glycerol
-Component in
thylakoid membrane
(chloroplast)
Glycolipid

Sulfolipids
-One sulfonated glucose residue connected to C3 of glycerol
-Component of plant cell membranes.
Sphingolipids
•Sphingolipds are composed of one molecule of long chain
of amino alcohol.
• Ceramide is a parent compounds of sphingolipids
I Sphingophospholipid: ceramides containing either
phosphocholine or phosphoethanolamine
-Sphingomyelins is similar to phosphatidylcholine component
in plasma membrane of animal cells surrounding the axon
(myelin sheath) of neuron for insulation some positions for
action potential.

Sphingosine
Sphingolipids

II Sphingoglycolipids: ceramides head groups (no phosphate)


that consist of a single sugar residue or more than one residue.
-Component of plasma membrane in neuron tissues, brain and
certain carbohydrate moieties representing the human
blood group

-Cerebroside; head group contains a single sugar residue


-Glangliosides; head group contains oligosacharides with
charateristic sugar derivatives, sialic acid (N-acetylneuraminidate)
Cerebrosides

Cerebrosides lack of phosphate


groups, and most of them are
nonionic compounds.

or β-D-glucose, glucocerebroside
Glangliosides
Sphingolipids
Steroids
•Eukaryotic origins
•Derivatives of cyclopentanoperhydrophenanthrene
•Most abundant in animals, cholesterol
•Cholesterol is a major component of plasma membranes but
lesser amounts in the membranes of subcellular organells.

C D

A B

Cyclopentanoperhydrophenanthrene
Sterols
•Plants contain sterol component in their membranes,
stigmasterol and β-sitosterols.
•Yeast and fungi have ergosterols as a membrane component.