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I.
II.
GENERAL DESCRIPTION
Polymeric molecules in which repeating unit is a nucleotide
Discovered by Swiss physiologist, Friedrich Miescher (1844-1895) in 1969 while studying the
nuclei of WBCs
The fact that they were initially found in the cell nuclei and were acidic accounts for the name
nucleic acid
TYPES OF NUCLEIC ACIDS
Phosphate
Base
Sugar
VARIABLE: A, U, C, G, T
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BASIS
Sugar
Bases
Strands
# of nucleotides
RNA
Ribose
Cytosine and Uracil
Single stranded
Much smaller than DNA molecules
DNA
Deoxyribose
Cytosine and Thymine
Double stranded
III.
(Fused ring)
(Single hetero cyclic ring)
FIGURE 2B General Structure of Nitrogen Bases
A. 3 PARTS OF NUCLEOTIDES:
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1. Pentose Sugar
Sugar unit of nucleotide is either the pentose ribose (RNA) or 2-deoxyribose (DNA)
2. Nitrogen-containing bases/Heterocyclic base
i.
Purine
o Bi-cyclic base with fused five-and-six member rings
a. Adenine (A): 6-amino-purine
b. Guanine (G): 2-amino-oxypurine
ii.
Pyrimidine
o Monocyclic base with a six-member ring
o RNA: Cytosine and Uracil
o DNA: Cytosine and Thymine
a. Thymine (T): 2,4-dioxy-5-methylpyrimidine
b. Cytosine (C): 2-oxy-4-aminopyrimidine
c. Uracil (U): 2,4-dioxypyrimidine
3. Phosphate
Third component of nucleotide, derived from phosphoric acid (H3PO4)
An important nucleotide is adenosine monophosphate (AMP) formed from a reaction of
adenosine (a nucleotide) and one molecule of phosphoric acid
B. NUCLEOTIDE FORMATION
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Important characteristics of this combining of three molecules into one molecule (nucleotide) are:
1. Dehydration (formation of water molecule) occurs at two locations: between the sugar and base,
and between the sugar and phosphate.
2. The base is always attached at the C1 position of the sugar. For purine bases, attachment is
through N9 for pyrimidine bases, N1 is involved. The C1 carbon atom of the ribose unit is always
in configuration.
3. The phosphate group is usually attached to the sugar at C5 position through the phosphateester-linkage
C. NUCLEOTIDE NOMENCLATURE
1. All of the names end in 5-monophosphate, which signifies the presence of a phosphate group
attached to the 5-carbon/atom of ribose or deoxyribose
2. Preceding the monophosphate ending is the name of the base present in the modified form. The
suffix osine is used for purine bases, the suffix idine with the pyrimidine bases.
3. The prefix deoxy at the start of the name signifies that the sugar present is deoxyribose, when
no prefix is used, the sugar is ribose.
4. The abbreviations in the table for the nucleotides come from the one-letter symbol for the bases
(A, C, G, T and U); the use of MP for monophosphate and a lower case d at the start of the
abbreviation whenever deoxyribose is the sugar
BASE
DNA Nucleotides
Adenine
Guanine
Cytosine
Thymine
RNA Nucleotides
Adenine
Guanine
Cytosine
Uracil
SUGAR
NUCLEOTIDE NAME
ABBREV.
Deoxyribose
Deoxyribose
Deoxyribose
Deoxyribose
Deoxyadenosine 5-monophosphate
Deoxyguanosine 5-monophosphate
Deoxycytidine 5-monophosphate
Deothymidine 5-monophosphate
dAMP
dGMP
dCMP
dTMP
Ribose
Ribose
Ribose
Ribose
Adenosine 5-monophosphate
Guanosine 5-monophosphate
Cytidine 5-monophosphate
Uridine 5-monophosphate
AMP
GMP
CMP
UMP
o
o
DNA Backbone
RNA Backbone
Deoxyribo
se
Phospha
te
Deoxyribos
e
Phospha
te
Deoxyribo
se
Ribose
Phospha
te
Ribose
Phospha
te
Ribose
3. Each non-terminal phosphate group in the backbone of a nucleic acid carries a -1 charge. The
parent phosphoric acid molecule from which the phosphate was derived originally had three
OH groups. Two of these become involved in the 3,5-phosphodiester linkage. The remaining
OH group is free to exhibit acidic behavior that is, to produce a H+ ion.
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BASE PAIRING
Chargaffs Rule
o Number of Purine molecules = Number of Pyrimidine molecules
A
=
T
G
C
Complementary Bases
o Specific pairs of bases in nucleic acid structures that hydrogen-bond to each other
o Two strands of DNA in double helix are not identical they are complementary (that
means if you know the order of bases in one strand, you can predict the order of
bases in the other strand).
o A mnemonic device for recalling base pairing combinations in DNA and RNA
involves listing the base in alphabetical order. Then the first and last bases pair, and
so the middle.
o DNA A
C
G
T
o RNA A
C
G
U
o In specifying base sequence of segment of strand of DNA or RNA, the bases are listed
in sequential order (using their one-letter abbreviations) in the direction from 5 end
to 3 end of the segment
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CHROMOSOMES
Individual DNA molecule bound to a group of molecule
These are nucleoproteins; they are combinations of nucleic acid (DNA) and various proteins.
15% by mass DNA and 85% by mass proteins
FIGURE 6A Chromosomes
DNA REPLICATION
Process by which DNA molecules produce exact duplicates of themselves.
Prior to division, cell has to duplicate its DNA
Semi-conservative replication
o Produces two new DNAs (daughter strand DNAs) identical to each other and exact copies
of the original parent DNA
o Strands are identical to original due to complementary base pairing
Complementary base pairing ensures the correct placement of bases in the new DNA strands
Helicase
o Unwinds/uncoils DNA helix and splits double strand
Single-Strand Binding Proteins (SSB)
o A single-strand binding-protein stabilizes the separated strands, and prevents them from
recombining, so that the polymerization chemistry can function on the individual strands.
DNA polymerase
o Catalyzes formation of phosphodiester bonds between the nucleotides
o Energy is provided to join each new nucleotide to the backbone of a growing DNA strand
o Catalyzes the replication process at each of these open DNA sections (replication forks)
o Catalyzes only phosphodiester bonds between the 5-phosphate of one of the nucleotide
and the 3-hydroxyl of the next, which means that DNA polymerases have to move in
opposite directions along the separated strands of DNA
Adds nucleotides in 5 3 direction (leading strand) movement towards
helicase (replication fork)
o Binds complementary bases
a. Leading strand
Replication is continuous
b. Lagging strand
Synthesized in the opposite direction
Formed in short segment of 100-200 nucleotides
Grows in direction of 53 because DNA polymerase III only works in the 53
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RNA Primase
o Places an RNA primer near fork
o Bonds the RNA nucleotides together
RNA primer
o Short sequence of RNA nucleotides, complementary to a small, initial section of the DNA
strand being prepared for replication
o Adds short RNA strand to DNA
Allows DNA polymerase to start on lagging strand
o Made by adding complimentary RNA nucleotides to the lagging DNA strand by hydrogen
bonding of the bases
RNA has U instead of T
o Enzymatically removed and replaced with an appropriate sequence of DNA nucleotides
DNA polymerase I
o Removes the RNA primers creating Okazaki fragments and replaces it with DNA
Okazaki fragments = short lengths of DNA formed between RNA primers
DNA ligase
o Adds DNA nucleotides to fill the gaps between Okazaki fragments and connect lagging
strand fragments by creating sugar-phosphate bond
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b. mRNA
o Carries genetic information (instructions for protein synthesis) from DNA to ribosome
o Messenger and its precursor 5-10%
o Primary Transcript RNA (ptRNA)
Material from which messenger RNA is made
c. tRNA
o Delivers specific individual amino acids to the ribosomes, the sites of protein synthesis
o Constitutes 10-15% cellular RNA
c. OVERVIEW OF PROTEIN SYNTHESIS 2 STEPS
DNA
A
G
C
T
RNA
U
C
G
A
d. TERMINATION
o Appearance in the mRNA codon sequence of one of the three stop codons terminates the
process
e. POST-TRANSLATION PROCESSING
o Some modification of proteins usually occurs after translation
THE GENETIC CODE
1. The genetic code is highly degenerated that is many amino acids designated by more than
one codon. Codons that specify the same amino acids are called synonyms
2. There is a pattern to the arrangement of the genetic code table
3. The genetic code is almost universal, the same codon specifies the same amino acid whether
the cell is a bacterial cell, a corn plant cell, or a human cell
4. An initiation codon exists
o The existence of stop codons suggests the existence of start codons
o The one initiation codon is AUG
First Position (5
end)
A
A
Lys
Asn
Lys
Asn
Gln
His
Gln
His
Glu
Asp
Glu
Asp
Stop
Typ
Stop
tyr
Second Position
C
G
U
Thr
Arg
Ile
Thr
Ser
Ile
Thr
Arg Met/Start
Thr
Ser
Ile
Pro
Arg
Leu
Pro
Arg
Leu
Pro
Arg
Leu
Pro
Arg
Leu
Ala
Gly
Val
Ala
Gly
Val
Ala
Gly
Val
Ala
Gly
Val
Ser
Stop
Leu
Ser
Cys
Phe
Ser
Trp
Leu
Ser
Cys
Phe
Third Position (3
end)
A
C
G
U
A
C
G
U
A
C
G
U
A
C
G
U
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GENETIC MUTATIONS:
Occurs if one of the code letters is omitted or if one is added or if the order of the code letters is
rearranged. Such a change in the sequence of nucleotides may:
1. Give no detectable effect, particularly of the change is in the third letter of the code.
2. Cause a different amino acid to be incorporated into the chain (the results may be
acceptable, or totally unacceptable to the function of the protein)
3. Cause the termination of the chain prematurely so that the protein cannot normal.
Causes:
1. Exposure to radiation
2. Because of naturally occurring radiation and cosmic rays
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4. GALACTOSEMIA
Results from the lack of enzyme uridyl transferase, which catalyzes the formation of glucose
from galactose. This disease may result in an increased concentration of galactose in the blood.
Galactose in the blood is reduced in the eye to galacticol, which accumulates and causes a
cataract, even liver failure and mental retardation will occur.
Transfer of enzyme requuired for the metabolism of glucose-1-phosphate is absent.
Accumulation of Gal-1-P leads to cataracts and mental retardation.
Treatment Administration of galactose free diet
5. WILSONS DISEASE
Caused by the bodys failure to eliminate excess Cu 2+ ions because of a lack of ceruplasmin or
failure in the bonding of copper ions to the copper-bonding globulin or both. In this disease,
copper accumulates in the liver, kidneys and brain. Increased copper in the kidneys may lead to
damage of the renal tubules, leading to increased urinary output of amino acids and peptides.
6. ALBINISM
Caused by lack of enzyme tyrosinase, which is necessary for the formation of melanin, the
pigment of the hair, skin, and eyes. Although the disease is not serious, persons affected by it are
very sensitive to sunburn.
7. HAEMOPHILIA
Caused by a missing protein, an antihemophilic globulin, which is important in the normal
clotting process of the blood. Consequently, any cut may be life threatening to hemophiliacs, but
the primary damage is the crippling effect of repeated episodes of internal bleeding into body
joints.
One or more defective blood clotting factors lead to poor coagulation, excessive bleeding, and
internal hemmorhages.
8. MUSCULAR DYSTROPHY (MD)
Duchennes muscular dystrophy, one of 10 forms of MD, is caused by the lack of protein called
dystrophin, as caused by a mutation in the X chromosome. This disease primarily affects boys at
about age 5 with death by age 20. It causes progressive weakness and muscle wasting.
9. DOWN SYNDROME
The leading cause of mental retardation, occuring in about 1 in every 100 live births, although
the mothers age strongly influences its occurrence. Mental and physical problems including
heart and eye defects are the result of the formation of three chromosomes, usually
Chromosome 21, instead of a pair.
10. FAMILIAL HYPOCHOLESTEREMIA
A mutation of a gene on chromosome 19 results in high cholesterol levels that leads to early
Coronary Heart Disease in people 30-40 years old.
11. HUNTINGTONS DISEASE (HD)
Appearing in middle age, affects the nervous system, leading to total physical impairment. It is
the result of a mutation in a gene on chromosome 4, which can now be mapped to test people in
families with HD.
12. TAY-SACHS DISEASE
Hexosamindase A is defective, causing an accumulation of gangliosides resulting in mental
retardation, loss of motor control, and early death.
TREATMENT OF GENETIC DISEASES:
1. Correct the metabolic consequences of the disease by supplying the missing product.
2. Replace the missing enzyme or hormone.
3. Remove excessive stored substances
4. Correct the major genetic abnormality.
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