You are on page 1of 7

Allan Jay Domingo, MD, Cell YL5:02.

04 7/4/2013

CELL
Nucleic Acids
OUTLINE
I. Nitrogenous Bases B. Nucleosome
A. Purines C. Histones
B. Pyrimidines D. DNA
II. Nucleosides E. Nucleotide Pairing
A. Definition F. Significance of
B. Properties of Base Pairing
Nucleosides G. DNA Helix is Anti-
C. Naming Nucleosides parallel
III. Nucleotides H.Chemistry of DNA o where X=H
A. Definition I. Configurations of
B. Cyclic Nucleotides DNA 3. Minor Purines
C. Nucleotides VI. RNA Synthesis • 2-Methyladenine
Diphosphate and A. Transcription • 2-Methylguanine
Triphosphate B. Classes of
D. Synthetic Nucleotide Eukaryotic DNA
Analogs C.Classes of RNA
IV. Nucleic Acids VII. Review Questions B. PYRIMIDINES
A. Definition VIII. References  Six-membered heterocyclic aromatic rings
V. DNA Structure and containing two nitrogen atoms
Function  Relatively insoluble in water
A. Chromosome
 Strong absorbance of ultraviolet light due to the
Structure
planar characteristic of the chemical structure
 the r-group in each pyrimidine nitrogenous base is
distinct
I. NITROGENOUS BASES (N-BASES)
1.Thymine (T) [found in DNA]
A. PURINE

 Nine-membered heterocyclic ring system consisting of


two rings, one resembling the pyrimidine ring and
another resembling the imidazol ring
 Relatively insoluble in water
 Strong absorbance of ultraviolet light due to the planar 2. Uracil (U) (found in RNA)
characteristic of the chemical structure
. 1. Adenine (A)
• amine group in the carbon 6

3. Cytosine (C)

2. Guanine (G)
• oxygen in carbon 6

Other examples of nitrogenous bases:


 S-adenosyl-methionine is a purine that gives the
methyl subgroup during methylation
TRANSCRIBED BY GROUP # 8 Asetre, Cruz, Fernandez, Gaña, Gemzon ,Hernandez, Ramos, Terre, Tien, Tolentino, Vergelde Dios, Yumol 1 OF 7
Allan Jay Domingo, MD, Cell YL5:02.04 7/4/2013

 Hypoxanthine, xanthine, uric acid


 Xanthine derivatives: caffeine (methlyxanthine),  Ribose is present in RNA while deoxyribose is present
theobromine and theophylline in DNA

 The structure of ribose and deoxyribose differ in that the


oxygen molecule attached to C2 of ribose is absent in
deoxyribose

 The syn and anti conformers of adenosine differ with


respect to the n-glycosidic bond.

B. PROPERTIES OF NUCLEOSIDES
 Initially hydrophobic but is much more water soluble
when bound to sugar due to hydrophilicity of the sugar
moiety
 Relatively stable in alkali
Structure of Caffeine
 Pyrimidines nucleosides – resistant to acid hydrolysis
 Purine nucleosides – easily hydrolyzed in acid

4. Uncommon in the Body: C. NAMING NUCLEOSIDES


 5-Methylcytosine and 5-Hydroxymethylcytosine  -idine for pyrimidines
 Dimethylaminoadenine and 7-methylguanine  Cytidine, uridine, thymidine
 -osine for purine
 Adenosine, guanosine, inosine
 In the DNA, (1) adenine, (2) guanine, (3)
Ex. Adenosine
cytosine and (4) thymine are present
 both naturally occurring and at the same
 In the RNA, (1) adenine, (2) guanine, (3)
time has pharmacologic clinical uses
cytosine and (4) uracil are present
 Also functions as an autocoid or “local
hormone: and as a neuromodulator
 actively secreted in the vessels of the
body, mostly in arteries
II. NUCLEOSIDES  Blood vessel dilation, smooth muscle
contraction, neuronal discharge,
A. DEFINITION neurotransmitter release and fat
metabolism
 Compounds formed when a nitrogenous base is  Blocks flow of electrical excitation by SA
linked to a sugar, specifically pentoses (C1 of sugar node in hear thus slowing heart rate as a
linked to N1 of pyrimidine or N9 of purine base) treatment in supraventricular tachycardia
 Pentose is a five membered ring form known as  Also implicated in sleep regulation wherein
furanose increase in levels of adenosine promotes
 Glycosidic bond sleepiness
 C-1’ to N-1 of a pyrimidine  Caffeine blocks the interaction of
 C-1’ to N-9 of a purine extracellular adenosine with its neural
 receptors
 Can either be an alpha or beta depending  used in pharmacologic stress testing
on their orientation relative to the anomeric
C atom
 Having syn (the molecules on the III. NUCLEOTIDES
glycosidic bond are at the same side in
terms of planar orientation) and anti (the A. DEFINITION
molecules on the glycosidic bond are at
opposite sides in terms of planar
 Nucleoside linked to a phosphate
orientation) configurations
 Phosphoric acid is esterified to a sugar OH group of
a nucleoside
 Ribose ring has three OH groups: 2’, 3’ and 5’
 Deoxyribose ring only has two: 3’ and 5’
 Sugar is linked to the nitrogenous base via a
glycosidic bond

TRANSCRIBED BY GROUP # 8 Asetre, Cruz, Fernandez, Gaña, Gemzon ,Hernandez, Ramos, Terre, Tien, Tolentino, Vergelde Dios, Yumol 2 OF 7
Allan Jay Domingo, MD, Cell YL5:02.04 7/4/2013

 Protons are shed if the negatively charged


phosphate groups are attached to each other
(cataionic)
 Can form stable complexes with divalent cations
such as Mg and Ca (bonds with the negatively-
charged phosphate group)
 Examples:
 ATP – energy currency of the cell
 GTP – major energy source for protein
synthesis
 CTP – essential metabolite in phospholipid
General Structure of a nucleotide synthesis
 UTP – forms activated intermediates in
glycogen synthesis
D. SYNTHETIC NUCLEOTIDE ANALOGS
 Used in cancer chemotherapy
 5-fluorouracil, 5-iodouracil, 3-deoxyuridine,
6-theioguanin and 6-mercaptopurine, 5- or
6- azauridine, 5- or 6- azacytidine, and 8-
azaguanine
 Other clinical treatments and biological functions
 Allopurinol is used in treatment of
hyperuricemia and gout by inhibiting puring
biosynthesis and axanthin oxidase activity
 Cytarabine is used for cancer treatment
 Azathioprine is used in organ transplant

 Ex: Adenosine-5’-monophosphate
 Adenosine-5’-diphosphate
 Adenosine-5’-triphosphate (major energy source)

 Acyclovir – anti-viral medication for several clinical


B. CYCLIC NUCLEOTIDES uses like herpes simplex virus and chickenpox
 Nucleoside monophosphate in which phosphoric  The phosphate group is cleaved out before the
acid is esterified to 2 of available ribose hydroxyl synthetic chemical structures are added, making
groups the product a synthetic analog coming from a
 cyclic linkage between the phosphate group and 2C nucleotide
or 5C of sugar moiety

IV. NUCLEIC ACIDS (NA)

A. DEFINITION

 Major genetic material in eukaryotes and


prokaryotes

 Linear polymers of nucleotides linked 3’ to 5’


by phosphodiester bridges

 Formed as 5’- nucleoside monophosphates are


C. NUCLEOTIDES DIPHOSPHATE AND TRIPHOSPHATE
successively added to the 3’- OH group of the
 Nucleotides with 2 or more phosphate groups preceding nucleotide
 Strong polyprotic acids in that they dissociate 3 and
4 protons from phosphoric acid groups that are  Two major classes
prime source of chemical energy  Ribonucleic acid (RNA)

TRANSCRIBED BY GROUP # 8 Asetre, Cruz, Fernandez, Gaña, Gemzon ,Hernandez, Ramos, Terre, Tien, Tolentino, Vergelde Dios, Yumol 3 OF 7
Allan Jay Domingo, MD, Cell YL5:02.04 7/4/2013

 Deoxyribonucleic acid (DNA) How was DNA structure identified?

V. DNA STRUCTURE AND FUNCTION


D. DNA
A. CHROMOSOME STRUCTURE  Contained in chromosomes
 Located in the nucleus  Double-helical structure
 46 chromosomes in the human eukaryotic cell (23  Linear for humans, mostly circular in viruses and
each from male and female) bacteria
 Short arm and long arm joined by centromere  Entire stretch has many genes that contain genetic
 Composed of tightly packed DNA code
surrounded by histones  6 ft long when stretched out
 Complexed with histones (proteins)
B. NUCLEOSOME  Negatively charged because of phosphate groups
 Part of the chromosome  Double-stranded with sugar-phosphate backbone
 Bead-like appearance  Nitrogenous bases make up the linear configuration
 Histone with DNA wound around (linear indicates stacking)
8 histone molecules + 146 nucleotide pairs of DNA  Sugar = deoxyribose that is attached to P and to
 2 of each H2A, H2Bm H3, H4; bases
H1 = linker DNA  Bases = adenine, guanine (purine); cytosine,
thymine (pyrimidine)
 Outer structure is hydrophobic and inner structure
is hydrophilic

C. HISTONES
 Positively charged
 Contains basic amino acids (Eg. Arginine and
lysine)

TRANSCRIBED BY GROUP # 8 Asetre, Cruz, Fernandez, Gaña, Gemzon ,Hernandez, Ramos, Terre, Tien, Tolentino, Vergelde Dios, Yumol 4 OF 7
Allan Jay Domingo, MD, Cell YL5:02.04 7/4/2013

 10 base pairs per turn, 3.4 nm in length (per turn)


 Width of DNA: 2 nm
 Forces in between bases for every turn stabilize
DNA molecule

H. CHEMISTRY OF DNA
 Forces affecting the stability of the DNA double
helix:
a. Hydrophobic interactions – stabilize
 Hydrophobic inside, hydrophilic outside
Stacking interactions –stabilize
 Relatively weak but additive van der Waals forces
Hydrogen bonding – stabilize
 Relatively weak but additive and facilitates stacking
Electrostatic interactions – destabilize
 Contributed primarily by the negative phosphates
E. NUCLEOTIDE PAIRING
 Affect intrastrand and interstrand interactions

Hydrogen bond between base pairs  Repulsion can be neutralized with the positive
 2H bonds for A-T charges (ex. Positively-charged Na+ ions or
 3H bonds for C-G proteins)
 DNA with more C-G base pairs have higher
melting point because of more bonds (through the I. CONFIGURATIONS OF DNA
process of denaturation)
 The number of adenosine is equal to the number of
thymine (in DNA) or uracil (in RNA) present, while the
 Generally 6 configurations found in nature (A, B, C,
number of guanine is equal to the number of cytosine
D, E and Z); but for humans, only A, B and Z are
(Chargaff’s rule)
present
 A-right handed, 2.8nm/turn (more compact than B
F. SIGNIFICANCE OF BASE PAIRING configuration)
 Determined mechanism of replication, transcription  B-right handed, 3.4nm. turn (most common for
and translation humans)
Replication – the process in which each strand  Z-left handed, zigzag appearance
of the original double-stranded DNA serves as template (We also have D and E)
for production of complementary strands
Transcription = RNA is formed from DNA
template
Translation = formation of protein
 mRNA – code
 rRNA – machinery that transcribes code by
mRNA
 tRNA – carry amino acids that synthesizes
protein

G. DNA HELIX IS ANTI-PARALLEL


 5’ to 3’ strand matched with 3’ to 5’ strand
 Each phosphate group links the 3’C of one sugar to
the 5’C of the next sugar along the backbone

TRANSCRIBED BY GROUP # 8 Asetre, Cruz, Fernandez, Gaña, Gemzon ,Hernandez, Ramos, Terre, Tien, Tolentino, Vergelde Dios, Yumol 5 OF 7
Allan Jay Domingo, MD, Cell YL5:02.04 7/4/2013

 Messenger RNA (mRNA)


 Comprises only 5% of total RNA in the cell
 Eukaryotic feautires: 5’-capping and addition of
polyA tail
 genetic coding templates used by translational
machinery to determine the order of amino acids that
are incorporated at an elongating polypeptide
 tRNA
 make up about 15% ot total RNA in the cell
 small RNAs that form covalent attachments to
individual amino acids
 recognize the encoded sequences of mRNAs to
allow the correct insertion of amino acids to the
elongating polypeptide chain
 clover-shaped
3’ end is where the amino acid is attached
5’ end codes for the anticodon

 Ribosomal RNA (rRNA)


 Make up 80% of total RNA in the cell
 Single stranded nucleotide
 assembled, together with numerous ribosomal
proteins to form the ribosomes
 ribosomes engage the mRNA and form a
catalytic domain into which tRNAs enter with their
attached amino acids

 Small nuclear ribonucleic acid (snRNA)


 Always associated with a set of specific proteins,
the complexes are referred to as small nuclear
ribonuclear proteins (snRNP or “snurps”)
VI. RNA SYNTHESIS (TRANSCRIPTION)

A. TRANSCRIPTION Difference in DNA between viruses and humans


(a) base pairing: viruses contain lesser base pairs than
 Mechanism by which a template strand of DNA is humans
used by specific RNA polymerase to generate 1-3 (b) conformation: viruses have a circular DNA
different classes of RNA conformation while humans have a linear DNA
conformation
B. CLASSES OF EUKARYOTIC RNA

Positive supercoiling of DNA occurs when the right-


handed, double-helical conformation of DNA is twisted
even tighter (twisted in a right-handed fashion). Negative
supercoiling, on the other hand, involves
twisting against the helical conformation (twisting in a
left-handed fashion), which preferentially underwinds and
"straightens" the helix at low twisting stress, and knots
the DNA into negative supercoils at high twisting stress.

Supercoiling is expected to occur in any process where


the DNA helix must be topographically linearized (i.e. the
helix must be uncoiled) for the function of a
macromolecular assembly. Transcription is a prime
example of such a situation, and topoisomerases are
indeed influential in regulating transcriptional
C. CLASSES OF RNA supercoiling.

 RNA is linear and single-stranded, but folds unto itself


through base pairing
 Areas with no occurrence of base pairing create hairpin
loops
TRANSCRIBED BY GROUP # 8 Asetre, Cruz, Fernandez, Gaña, Gemzon ,Hernandez, Ramos, Terre, Tien, Tolentino, Vergelde Dios, Yumol 6 OF 7
Allan Jay Domingo, MD, Cell YL5:02.04 7/4/2013

VII. REVIEW QUESTIONS http://genomealberta.ca/files/Education/dnatimelinef.jpg


http://www.vce.bioninja.com.au/_Media/picture_2_med.jpeg

1. Select the components and bonding present in


RNA.
a. Nitrogen bases; deoxyribose;
phosphodiester bonds
b. Nitrogen bases; ribose;
phosphodiester bonds
c. Nitrogen bases; deoxyribose; N-
glycosidic bonds
d. Nitrogen bases; ribose; amide bonds
2. When Chargaff analyzed the concentration of
bases in DNA, he found that:
a. A = T; G = C
b. A = G; T = C
c. A + C = T
d. A = T = C = G
3. The double helix as determined by Watson and
Crick is composed of
a. Two, parallel complementary strands
b. Two, antiparallel complementary
strands
c. A single strand of phosphodiester
linkages
d. Two strands in α-helix conformation
4. Which of the following reagents and/or conditions
will denature double-stranded DNA?
a. Heat
b. Urea
c. Extreme pH changes
d. All of the above
5. True or False: A nucleotide forms when a
phosphoryl group is linked to a carbohydrate
hydroxyl group on the nucleoside.
a. True
b. False
Study the structure of the oligonucleotide below and answer
the following questions.

1. What is the nitrogen base at the 5’ end? adenine


2. Is this molecule RNA or DNA? DNA
3. What is the structure for the complementary
oligonucleotide? 3’TACG

VIII. REFERENCES AND ADDITIONAL READING

Read chapters 34 and 35 for the test


http://www.callutheran.edu/BioDev/omm/topo1/frames/coil.ht
m
http://1.bp.blogspot.com/vf7nGEouIOo/UNc5DLd_o_I/AAAAAA
AAAac/veTGWgsGawY/s640/RNA+metabolism.bmp
TRANSCRIBED BY GROUP # 8 Asetre, Cruz, Fernandez, Gaña, Gemzon ,Hernandez, Ramos, Terre, Tien, Tolentino, Vergelde Dios, Yumol 7 OF 7

You might also like