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Nucleic acids
Nucleosides & Nucleotides
Nucleic Acids
DNA & Replication
RNA & Transcription
Genetic Code & Protein Synthesis
Genetic Mutations
Recombinant DNA
Viruses
©Chemistry for Allied Health: Chap 22 - DNA
21 - 1
Nucleic acids
Nucleic acids:
– Maintain genetic information
– Determine Protein Synthesis
DNA = deoxyribonucleic acid
– “Master Copy” for most cell information.
– Template for RNA
RNA = ribonucleic acid
– Transfers information from DNA
– Template for Proteins
©Chemistry for Allied Health: Chap 22 - DNA
21 - 2
Nucleic Acids
In chromosomes
(in nucleus)
Have genes
1 gene
1 enzyme
Enzymes determine
external & internal characteristics
©Chemistry for Allied Health: Chap 22 - DNA
21 - 3
NUCLEIC ACIDS
Long chains (polymers) of repeating nucleotides.
– Each nucleotide has 3 parts:
A heterocyclic
Amine Base
N
O
HO P OH
H
HO
O
O
OH
H
A phosphate unit
H
H
H
OH
©Chemistry for Allied Health: Chap 22 - DNA
H
A sugar
H
21 - 4
Nucleotide = phosphate + sugar + base
Phosphate
Base
O
O P
N
Sugar
O
O
O
H
-N-glycosidic
linkage
H
H
H
OH
H
Nucleoside = sugar + base
©Chemistry for Allied Health: Chap 22 - DNA
21 - 5
Nucleic Acids
Nucleic Acids = polymers of Nucleotides.
base
B
P
S
B
P
S
B
P
S
B
P
phosphate
©Chemistry for Allied Health: Chap 22 - DNA
S
B
B
P
S
P
S
sugar
21 - 6
THE SUGAR PART
• The major difference between RNA and DNA is
the different form of sugar used.
Ribose C5H10O5
in RNA
O
HOCH2
H
OH
H
H
OH
OH
H
DeoxyRibose C5H10O4
in DNA
O
HOCH2
H
OH
H
H
OH
H
H
The difference is at carbon #2.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 7
The Nitrogenous Bases
5 bases used fall in two classes
Purines
&
N
N
N
N
Pyrimidines
N
N
H
A double ring
A single ring
(6 & 5 members)
(6 membered)
©Chemistry for Allied Health: Chap 22 - DNA
21 - 8
The Nitrogenous Bases
NH2
Purines:
N
N
Adenine (A)
O
N
H
N
H2N
H
N
H
Thiamine (T)
In DNA only
©Chemistry for Allied Health: Chap 22 - DNA
N
N
H
NH2
O
CH3
N
N
N
Guanine (G)
O
Pyrimidines:
H
O
H
O
H
N
N
H
Uracil (U)
In RNA only
O
N
N
H
Cytosine (C)
21 - 9
Nucleotides
deoxyadenosine 5’ monophosphate
(dAMP)
NH2
N
N
O
O P
O
Name based on
sugar & base names
followed by the #
of phosphates..
©Chemistry for Allied Health: Chap 22 - DNA
N
N
O
5'
O
4' H
H
3'
OH
H
1'
H
2'
H
21 - 10
Primary structure
NH2
|
C
O
|
- O -- P -- O -- CH
2
||
O
N
C
HC
C
CH
N
N
NH2
|
C
O
N
O
|
- O -- P -- O -- CH
2
||
O
Phosphate bonds
link DNA or RNA
nucleotides together
in a linear sequence.
©Chemistry for Allied Health: Chap 22 - DNA
Similar to proteins
with their peptide
bonds and side
groups.
N
CH
C
O
CH
N
O
||
C
O
O
|
- O -- P -- O -- CH
2
||
O
HN
C
C
C
N
CH
H2N
N
N
O
||
C
O
HN
O
|
- O -- P -- O -- CH
2
||
O
C
C
O
CH3
CH
N
O
OH
21 - 11
DNA - Primary Structure
©Chemistry for Allied Health: Chap 22 - DNA
21 - 12
Base pairing and H-bonding
H- bonding between purines and pyrimidines..
N
H-N
N
N-H
guanine
N
N
cytosine
N
N-H
H 3C
H
thymine
N
H
|
N- H
N
N
adenine
N
N
©Chemistry for Allied Health: Chap 22 - DNA
N
21 - 14
DNA - Secondary Structure
Complementary Base Pairing
Guanine pairs with Cytosine
Position of H bonds and distance match
©Chemistry for Allied Health: Chap 22 - DNA
21 - 15
DNA - Secondary Structure
Complementary Base Pairing
Adenine pairs with Thymine
Position of H bonds and distance match
©Chemistry for Allied Health: Chap 22 - DNA
21 - 16
Hydrogen bonding
Each base wants to
form either two or three
hydrogen bonds.
That’s why only certain
bases will form pairs.
C
G
T
A
G
C
G
A
©Chemistry for Allied Health: Chap 22 - DNA
C
T
21 - 17
Sugarphosphate
backbone
DNA coils
around
outside of
attached
bases like
a spiral
stair case.
Results in a double helix structure.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 18
The double helix
The combination of
the stairstep sugarphosphate backbone
and the bonding
between pairs results
in a double helix.
Distance between
bases = 0.34 nm
©Chemistry for Allied Health: Chap 22 - DNA
One
complete
twist
is 3.4 nm
2 nm
between
strands
21 - 19
DNA - Secondary Structure
Complementary Base Pairing
©Chemistry for Allied Health: Chap 22 - DNA
21 - 20
• The actual chain is like a coiled spring.
– It is something similar to what happens when
protein chains form an alpha helix.
• It is the sequence (order) of the amines coming
off of the backbone that give us all our genetic
information
– Just like the sequence of words in a sentence
give it meaning.
– Of the like in words meaning just sentence a
give sequence it. (Get my meaning ? )
©Chemistry for Allied Health: Chap 22 - DNA
21 - 21
• Crick and Watson
(1962 Nobel Prize)
– Proposed the basic
structure of DNA
– 2 strands wrap around
each other
– Strands are connected by
H-bonds between the
amines.
• Like steps of a spiral
staircase
©Chemistry for Allied Health: Chap 22 - DNA
21 - 22
Chromosomes
Chromosomes consists of DNA strands coiled
around protein - histomes. The acidic DNA’s are
attracted to the basic histones.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 23
©Chemistry for Allied Health: Chap 22 - DNA
21 - 24
Chromosomes
The normal number of chromosome pairs varies
among the species.
Animal
Man
Cat
Mouse
Rabbit
Honeybee,
male
female
Pairs
23
30
20
22
8
16
©Chemistry for Allied Health: Chap 22 - DNA
Plant
Onion
Rice
Rye
Tomato
White pine
Adder’s
tounge fern
Pairs
8
14
7
12
12
1262
21 - 25
DNA: Self - Replication
• When a cell nucleus divides, the bridging
hydrogen bonds break (with the aid of
enzymes) and the intertwined strands unwind
from each other.
• The amines left sticking out from each strand
are now free to pick up new partners from the
plentiful supply present in the cell.
P
P
P
P
S
S
S
S
A
T
G
C
amine bases hanging off the nucleotide chain.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 26
Each A picks up a T, each C picks up a G, etc...
P
P
P
P
S
S
S
S
A
T
G
C
T
P
S
G
P
S
Eventually, every amine group is reunited with
its complimentary amine and the lost partner strand
is reformed.
They now twine around each other to form the
new Double helix.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 27
DNA Replication
©Chemistry for Allied Health: Chap 22 - DNA
21 - 28
Replication of DNA
Replication occurs on both halves
in opposite directions.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 29
DNA Replication
©Chemistry for Allied Health: Chap 22 - DNA
21 - 30
DNA Replication
Okazaki fragments
©Chemistry for Allied Health: Chap 22 - DNA
21 - 31
DNA Replication
Okazaki fragments
©Chemistry for Allied Health: Chap 22 - DNA
21 - 32
• It is the linear sequence of paired bases
(amines) along the DNA molecule that
constitutes the Genetic Code.
– Each series of amines that codes for a
particular protein is called a Gene.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 33
Flow of genetic information
DNA
Replication
Transcription
RNA
Translation
Protein
©Chemistry for Allied Health: Chap 22 - DNA
Flow of
information
is
one way
only.
21 - 47
RNA
Single strands of nucleotides where ribose is
used in the sugar-phosphate backbone.
Several secondary structures (types) based on
the particular role it plays.
RNA is produced by transcription of genes
along a strand of DNA.
DNA may contain all the information but RNA
does all of the work. (Kinda like the architect and the
engineer. Or better yet, the teacher and the student. )
©Chemistry for Allied Health: Chap 22 - DNA
21 - 48
Classes of RNA
Messenger RNA - mRNA
It carries a copy of the genetic information
contained in DNA. Used as pattern to make
proteins.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 49
RNA - THE MESSENGER (m/RNA)
• DNA in the nucleus of the cell directs the
sythesis of an RNA molecule.
– The RNA will carry the sequence of amines
found on a particular portion of the DNA
• Only a portion of a DNA strand is used to make
any given RNA.
• There needs to be a way to start and stop
transcription.
• The DNA has systems of promoter and
termination base sequences.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 50
RNA synthesis
In the first step,
RNA polymerase binds
to a promotor sequence
on the DNA chain.
This insures that
transcription occurs in
the correct direction.
The initial
reaction is to
separate the two
DNA strands.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 51
RNA synthesis
initiation
sequence
termination
sequence
‘Special’ base
sequences in the
DNA indicate
where RNA
synthesis starts
and stops.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 52
RNA synthesis
Once the
termination
sequence is
reached, the
new RNA molecule
and the
RNA synthase
are released.
The DNA recoils.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 53
• The messenger RNA (mRNA) move
outside the nucleus to the cytoplasm
where Ribosomes are anxiously awaiting
their arrival.
60 S
rRNA
rRNA
40 S
©Chemistry for Allied Health: Chap 22 - DNA
21 - 54
• The messenger RNA (mRNA) move
outside the nucleus to the cytoplasm
where Ribosomes are anxiously awaiting
their arrival.
60 S
rRNA
rRNA
40 S
©Chemistry for Allied Health: Chap 22 - DNA
21 - 55
• The messenger RNA (mRNA) move
outside the nucleus to the cytoplasm
where Ribosomes are anxiously awaiting
their arrival.
60 S
rRNA
rRNA
40 S
©Chemistry for Allied Health: Chap 22 - DNA
21 - 56
• The messenger RNA (mRNA) move
outside the nucleus to the cytoplasm
where Ribosomes are anxiously awaiting
their arrival.
60 S
rRNA
rRNA
40 S
©Chemistry for Allied Health: Chap 22 - DNA
21 - 57
Ribosomal RNA – rRNA: Platform for protein
synthesis. Holds mRNA in place and helps
assemble proteins.
60 S
rRNA
rRNA
40 S
©Chemistry for Allied Health: Chap 22 - DNA
21 - 58
•The Ribosomes are like train stations
–The mRNA is the train slowly moving
through the station.
60 S
rRNA
Codons
AUG
GCU
AUG
5’
UUG
3’mRNA
rRNA
40 S
©Chemistry for Allied Health: Chap 22 - DNA
21 - 59
Transfer RNA - tRNA =
• relatively small compared to other RNA’s
(70-90 bases.)
• transports amino acids to site of protein
synthesis.
HO-
A
C
C
A
G
G
A U G
U
C
G
G U A
C G C G G
U
C
G
C
G
U
C
G
G
C
U
U
G
C A G G
C C
U C C
G G
C
C G
C
U
G
U
A
G
G C G C
U
U U
C
G A G
U
A
C
G
C
G
C
G
G
G
C G C
©Chemistry for Allied Health: Chap 22 - DNA
21 - 60
Anticodons on t-RNA
HO-
C
Site of amino
acid attachment
G
A
U
G
U
C
G
G U
A
C G
G
Three base
anticodon site
C
C
A
C
G
G
U
G
C
G
C
G
U
C
G
G
C
U
U
G
C
A
G
G
C
C
U
U
A
G
U
C
G C
C
C
G
G
C
G
C
U
G
C
G
U
A
C
G
C
G
C
G
A
U
G
U
G
C
©Chemistry for Allied Health: Chap 22 - DNA
A
G
C
G
Point of
attachment
to mRNA
21 - 61
Amino acid codons
alanine
GCA, GCC, GCG
GCU, AGA, AGG
arginine
AGA, AGG, CGA
CGC, CGG, CGU
asparagine AAC, AAU
aspartate
GAC, GAU
cysteine
UGC, UGU
glutamate GAA, GAG
glutamine CAA, CAG
glycine
GAA, GCC, GGG
GGU
histidine
CAC, CAU
isoleucine AUA, AUC, AUU
leucine
CUA, CUC, CUG
CUU, UUA, UUG
©Chemistry for Allied Health: Chap 22 - DNA
lysine
AAA, AAG
methionine
AUG
phenylalanine UUC, UUU
proline
CCA, CCC
CCG, CCU
serine
UCA, UCC
UCG, UCU
AGC, AGU
threonine
ACA, ACC
ACG, ACU
tryptophan
UGG
tyrosine
UCA, UCU
valine
GUA, GUC
GUG, GUU
21 - 62
Protein Synthesis
1: Activation
Each AA is activated by reacting with an
ATP
The activated AA is then attached to
particular tRNA... (with the correct anticodon)
activated AA
anticodon
©Chemistry for Allied Health: Chap 22 - DNA
fMET
C
G
A
21 - 63
NH2
Aa +
N
N
O
O P
O
©Chemistry for Allied Health: Chap 22 - DNA
N
O
N
5'
O
1'
4' H
H
H
H
2'
3'
H
OH
adenosine 5’ triphosphate
(ATP)
21 - 64
Translation
AUG
Initiation
factors
5’
GCU
AUG
UUG
mRNA
3’
Psite A site
40S ribosome unit
©Chemistry for Allied Health: Chap 22 - DNA
21 - 65
Translation
fMET
U A C
AUG
Initiation
factors
5’
GCU
AUG
UUG
mRNA
3’
Psite A site
40S ribosome unit
©Chemistry for Allied Health: Chap 22 - DNA
21 - 66
Translation
fMET
60S
U A C
AUG
5’
GCU
AUG
UUG
mRNA
3’
Psite A site
40S ribosome unit
©Chemistry for Allied Health: Chap 22 - DNA
21 - 67
Translation
Ala
fMET
60S
C G A
U A C
AUG
5’
GCU
AUG
UUG
mRNA
3’
Psite A site
40S ribosome unit
©Chemistry for Allied Health: Chap 22 - DNA
21 - 68
Translation
peptide bond
forms
fMET
Ala
U A C
C G A
AUG
GCU
AUG
UUG
mRNA
3’
5’
ribosome unit
©Chemistry for Allied Health: Chap 22 - DNA
21 - 69
Translation
peptide bond
forms
fMET
Ala
U A C
C G A
AUG
GCU
AUG
UUG
mRNA
3’
5’
ribosome unit
©Chemistry for Allied Health: Chap 22 - DNA
21 - 70
Translation
Amino Acid
peptide bond
Met
Ala
Z Z Z
C G A
GCU
UUC
UUG
mRNA
3’
5’
ribosome unit
©Chemistry for Allied Health: Chap 22 - DNA
21 - 71
Translation
peptide bond
forms
Met
Ala
???
C G A
? ?
?
GCU
UUC
UUG
mRNA
3’
5’
ribosome unit
©Chemistry for Allied Health: Chap 22 - DNA
21 - 72
Termination
After the last translocation (the last
codon is a STOP), no more AA are
added.
“Releasing factors” cleave the last
AA from the tRNA
The polypeptide is complete
©Chemistry for Allied Health: Chap 22 - DNA
21 - 73
Codons
There are two additional types of codons:
Initiation
AUG
(same as methionine)
Termination
UAG, UAA, UGA
A total of 64 condons are used for all amino
acids and for starting and stopping. All protein
synthesis starts with methionine. After the polypeptide has been made, an enzyme removes this
amino acid.
©Chemistry for Allied Health: Chap 22 - DNA
21 - 74
Amino acid codons
alanine
GCA, GCC, GCG
GCU, AGA, AGG
arginine
AGA, AGG, CGA
CGC, CGG, CGU
asparagine AAC, AAU
aspartate
GAC, GAU
cysteine
UGC, UGU
glutamate GAA, GAG
glutamine CAA, CAG
glycine
GAA, GCC, GGG
GGU
histidine
CAC, CAU
isoleucine AUA, AUC, AUU
leucine
CUA, CUC, CUG
CUU, UUA, UUG
©Chemistry for Allied Health: Chap 22 - DNA
lysine
AAA, AAG
methionine
AUG
phenylalanine UUC, UUU
proline
CCA, CCC
CCG, CCU
serine
UCA, UCC
UCG, UCU
AGC, AGU
threonine
ACA, ACC
ACG, ACU
tryptophan
UGG
tyrosine
UCA, UCU
valine
GUA, GUC
GUG, GUU
21 - 75
Recombinant DNA
Circular DNA found in bacteria
E.Coli plasmid bodies
Restriction endonucleases cleave DNA at
specific genes
Result is a “sticky end”
Addition of a gene from a second
organism
Spliced DNA is replaced and organism
synthesizes the new protein
©Chemistry for Allied Health: Chap 22 - DNA
21 - 87
Recombinant DNA
Bacterium
Remove
gene segment
DNA
Plasmid
sticky ends
Cut gene
for insulin
Replace in
bacterium
©Chemistry for Allied Health: Chap 22 - DNA
21 - 88