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 CHAPTER 22: Nucleic Acids & Protein Synthesis General, Organic, & Biological Chemistry Janice Gorzynski Smith CHAPTER 22: Nucleic Acids & Protein Synthesis
Learning Objectives:
q  Nucleosides & Nucleo@des: structure q  DNA & RNA base pairs: names & structures q  Phosphate addi@on q  Nucleic Acids q  Forma@on & primary structure q  DNA double helix structure, hydrogen bonding q  Replica@on, Transcrip@on, Transla@on q  RNA q  rRNA, mRNA, tRNA q  Gene@c Code: codon & an@codon q  Protein Synthesis: ini@a@on, elonga@on, termina@on q  Muta@ons q  Recombinant DNA: forma@on & use CH 22 Homework:
End of Chapter problems: 32, 36, 38, 44, 48, 50, 54, 62, 64, 68, 70, 76,
Smith, Janice Gorzynski. General, Organic, 78, 82, 88, 94, 100 & Biological Chemistry 2nd Ed. 2 Nucleic Acids
Overview
• Nucleic acids are unbranched polymers composed
of repeating monomers called nucleotides.
• There are two types of nucleic acids: DNA and
RNA.
• DNA (deoxyribonucleic acid) stores the genetic
information of an organism and transmits that
information from one generation to another.
• RNA (ribonucleic acid) translates the genetic
information contained in DNA into proteins needed
for all cellular function.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 3 Nucleotides
Definition
• The nucleotide monomers that compose DNA and
RNA consist of: a monosaccharide, a N-containing
base, and a phosphate group:
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 4 Nucleic Acids
Overview
• DNA molecules contain several million nucleotides,
while RNA molecules have only a few thousand.
• DNA is contained in the chromosomes of the
nucleus, each chromosome having a different type
of DNA.
• Humans have 46 chromosomes (23 pairs), each
made up of many genes.
• A gene is the portion of the DNA molecule
responsible for the synthesis of a single protein.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 5 Nucleosides
Definition
• A nucleoside consists of: a monosaccharide and a
N-containing base:
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 6 Nucleosides
The Monosaccharide
• In RNA the monosaccharide is the aldopentose
D-ribose.
• In DNA, the monosaccharide is the aldopentose
D-2-deoxyribose.
7 Nucleosides
The N Containing Base
• The N-containing base is one of 5 types.
• Cytosine (C), uracil (U), and thymine (T) are all
based on the structure of pyrimidine.
8 Nucleosides
The N Containing Base
• Adenine (A) and guanine (G) are based on the
structure of purine.
• DNA contains bases A, G, C, and T.
• RNA contains bases A, G, C, and U.
9 ides—Joining a Nucleoside with a Phosphate
Comparison
with Nucleosides
ed by addingNucleotides
a phosphate group to the
5'-OH of a nucleoside.
Nucleoding the term 5'-monophosphate to the name of the nucleoside from which
onucleotides are
from are
ribose,
while by
deoxyribonucleotides
are
• Nderived
ucleotides
formed
adding a phosphate
ibose.
group to the 5′-OH of a nucleoside.
NH2
N
N
O
−O
O
P
O
5'
CH2
N
O
O
CMP
O−
OH
OH
cytidine 5'-monophosphate
a ribonucleotide
NH2
• The name cytidine 5′-monophosphate is
NH2
abbreviated as CMP.
N
N
Smith, Janice Gorzynski. GN
eneral, Organic, & Biological Chemistry 2nd Ed. O
−O
P
O
5'
CH2
O
N
N
10 N
dAMP
OH
OH
cytidine 5'-monophosphate
a ribonucleotide
Comparison with Nucleosides
Nucleotides
NH2
N
NH2
N
N
O
−
O
P
O
5'
CH2
O
N
N
N
dAMP
O−
OH
deoxyadenosine 5'-monophosphate
a deoxyribonucleotide
names of nucleotides, three- or four-letter abbreviations are commonly
ine 5'-monophosphate is CMP and deoxyadenosine 5'-monophosphate
The name deoxyadenosine 5 -monophosphate is
abbreviated as dAMP.
the information about nucleic acids and their components learned thus
zes the names and abbreviations used for the bases, nucleosides, and
Smith, Janice Gorzynski. General, Organic, cleic acid chemistry.
& Biological Chemistry 2nd Ed. 11 O
four-letter abbreviation.
b. the sugar deoxyribose
O
d. the base U
f. the nucleotide d
O
CH
O
a.
−O
P
3
Di- and triphosphates
can also be prepared from nucleosides by adding two
NH
O groups, respectively, to the 5'-OH. For example, adenosine can be conver
phate
adenosine
5'-triphosphate,
abbreviated as ADP and ATP, r
N
O
P O CH2 and
b. −O 5'-diphosphate
O
will− learn about the central role of these phosphates, especially ATP, in energ
O
Chapter 23.
NH
O
Nucleotides
CH2
N
O
O−
Comparison with Nucleosides
O
• ADP is an example of a diphosphate:
OH
OH
OH
NH2
PROBLEM 22.4
N
O following
O components?
Which nucleic acid (DNA or RNA) contains each of the
5'
−O
N
CH
P
O
O
P
a. the sugar ribose
c. the base T
e. the 2nucleotide
GMP
O
b. the sugar deoxyribose
d. the base UO−
O− f. the nucleotide dCMP
OH
N
O
−O
N
P
O−
O
O
P
O−
O
O
O
P
OH
adenosine 5'-tri
ATP
• ATP is an example of a triphosphate:
NH2
N
O
P
O
5'
CH2
O
N
NH2
N
N
O−
O
−O
P
O−
smi02788_ch22_715-750.indd
720
OH
OH
adenosine 5'-diphosphate
ADP
O
O
P
O−
N
O
O
P
O
CH2
N
O
N
N
O−
OH
OH
adenosine 5'-triphosphate
ATP
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. O
O−
OH
Di- and triphosphates can also be prepared from nucleosides by adding two and three phosphate groups, respectively, to the 5'-OH. For example, adenosine
can be 5'-diphosphate
converted to adenosine
adenosine
5'-diphosphate and adenosine 5'-triphosphate, abbreviated as ADP andADP
ATP, respectively. We
will learn about the central role of these phosphates, especially ATP, in energy production in
Chapter 23.
CH2
12 of one nucleotide with the 5'-phosphate of a second nucleotide in a phosphodi(Section 19.6).
joining the 3'-OH group of dCMP (deoxycytidine 5'-monophosphate) and the
Definition
Nucleic Acids
of dAMP (deoxyadenosine 5'-monophosphate) forms a dinucleotide that contains
e on one end (called the 5' end) and a 3'-OH group on the other end (called the
• Nucleic acids (DNA and RNA) are polymers of
nucleotides joined by phosphodiester linkages.
A dinucleotide
NH2
5'-phosphate
N
O
−O
P
O
5'
CH2
N
O
O
NH2
O−
3'
O
N
phosphodiester
linkage
O
P
N
O
5'
CH2
O
N
N
N
O−
3'
OH
3'-OH
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 13 Nucleic Acids
Definition
• A polynucleotide contains a backbone consisting
of alternating sugar and phosphate groups.
• The identity and order of the bases distinguish
one polynucleotide from another (primary
structure).
• A polynucleotide has one free phosphate group
at the 5’ end and one free OH group at the 3 end.
• In DNA, the sequence of the bases carries the
genetic information of the organism.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 14 FIRST PAGES
NUCLEIC ACIDS AND PROTEIN SYNTH
Sugar-Phosphate Backbone
Nucleic
Acids
Figure 22.2 Primary Structure of a Polynucleotide
5'-phosphate
sugar–phosphate backbone
O
−
O
P
O
5'
CH2
O−
cytosine
5'-phosphate P
O
O
C
3'
O
O
P
O
P
5'
CH2
adenine
O
O
O−
A
=
3'
P
O
O
P
O
O
5'
CH2
−
O
thymine
O
P
3'
O
O
The phosphodiester linkage joins
the 3' C of one nucleotide to the
5' C of another nucleotide.
T
O
P
O
5'
CH2
O−
G
guanine
O
3'-OH
HO
3'
OH
3'-OH
15 Smith, Janice Gorzynski. General, Organic, In a polynucleotide, phosphodiester bonds join the 3'-carbon of one nucleotide to the 5'-carbon of another.
& Biological Chemistry 2nd Ed. The name of a polynucleotide is read from the 5' end to the 3' end, using the one-letter abbreviations for the
bases it contains. Drawn is the structure of the polynucleotide CATG.
Nucleic Acids
Naming Polynucleotides
• This polynucleotide
would be named CATG,
reading from the 5 end
to the 3 end.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 16 Definition
DNA
• DNA consists of two
polynucleotide strands that
wind into a right-handed
double helix.
• The two strands run in
opposite directions; one
runs from the 5 end to the
3 end and the other runs
from the 3 end to the 5
end.
• The sugar-phosphate
groups lie on the outside of
the helix and the bases lie
on the inside.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 17 DNA
Base Pairs
The bases always
line up so that a
pyrimidine
derivative can
hydrogen bond to
a purine
derivative on the
other strand.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 18 DNA
Base Pairs
hVp://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/Exam%201%20Review/
Ch02%20Nucleic%20Acids%20and%20ATP.htm. 19 DNA
OBLEM 22.4
Base Pairs
nce of the complementary strand of the following portion of a DNA molecu
• Adenine pairs with thymine with 2 hydrogen
'.
bonds to form an A—T base pair.
• Cytosine
pairs withdirection,
guanine using
3 hydrogen
ntary strand runs
in the opposite
from the
3' to the 5' end. Use b
bonds
to formon
a C—G
base pair.
e corresponding
sequence
the complementary
strand: A pairs with T an
2.9
Original strand: 5'–T A G G C T A–3'
Complementary strand: 3'–A T C C G A T–5'
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. ementary strand for each of the following strands of DNA.
20 DNA
Transcription, Translation, Replication
• The information stored in DNA is used to direct
the synthesis of proteins.
• Replication is the process by which DNA makes
a copy of itself when a cell divides.
• Transcription is the ordered synthesis of RNA
from DNA; the genetic information stored in DNA
is passed onto RNA.
• Translation is the synthesis of proteins from RNA;
the genetic information determined the specific
amino acid sequence of the protein.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 21 DNA
Replication
Before replication
A replication fork forms as the
2 strands split apart
Synthesis of the lagging
strand
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 22 DNA
Replication
Enzymes involved in DNA replica@on: DNA Helicase, DNA Plymerase, DNA clamp, Single-­‐
Strand Binding Proteins, Topoisomerase, DNA Gyrase, DNA Ligase, Primase, & Telomerase hVp://en.wikipedia.org/wiki/
DNA_replica@on 23 DNA
Replication
• The identity of the bases on the template strand
determines the order of the bases on the new
strand.
• A must pair with T, and G must pair with C.
• A new phosphodiester bond is formed between the
5 -phosphate of the nucleoside triphosphate and
the 3 -OH group of the new DNA strand.
• Replication occurs in only one direction on the
template strand, from the 3 end to the 5 end.
• The new strand is either a leading strand, growing
continuously, or a lagging strand, growing in
small fragments.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 24 RNA
Definition
• There are important differences between DNA and
RNA.
• In RNA, the monosaccharide is ribose.
• The thymine (T) base is not present in RNA;
instead, the uracil (U) base is used.
• RNA is a single strand, and smaller than DNA.
• The three types of RNA molecules are ribosomal
RNA (rRNA), messenger RNA (mRNA), and
transfer RNA (tRNA).
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 25 RNA
Definition
• Ribosomal RNA (rRNA) provides the site where
polypeptides are assembled during protein
synthesis.
• Messenger RNA (mRNA) carries the information
from DNA to the ribosome.
• Transfer RNA (tRNA) brings specific amino acids
to the ribosomes for protein synthesis.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 26 RNA
tRNA
tRNA is drawn as a cloverleaf shape, with an
acceptor stem at the 3 end, which carries the
needed amino acid, and an anticodon, which
identifies the needed amino acid.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 27 RNA
Transcription
• Transcription is the synthesis of mRNA from DNA.
• The DNA splits into two strands, the template
strand, which is used to synthesize RNA, and the
informational strand which is not used.
• Transcription proceeds from the 3 end to the 5
end of the template.
• Transcription forms a mRNA with a complementary
sequence to the template DNA strand and an
exact sequence as the informational DNA strand.
• The difference between mRNA and the information
DNA strand is that the base U replaces T on mRNA.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 28 RNA
Transcription
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 29 RNA
Genetic Code
• A sequence of three nucleotides (a triplet) codes
for a specific amino acid.
• Each triplet is called a codon.
• For example, UAC is a codon for the amino acid
serine; UGC is a codon for the amino acid cysteine.
• Codons are written from the 5’ end to the 3’ end of
the mRNA molecule
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 30 RNA
Genetic Code
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 31 RNA
Translation & Protein Synthesis
• mRNA contains the sequence of codons that
determine the order of amino acids in the protein.
• Individual tRNAs bring specific amino acids to
the peptide chain.
• rRNA contains binding sites that provide the
platform on which protein synthesis occurs.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 32 RNA
Translation & Protein Synthesis
• Related codons, anticodons, and amino acids:
• The three main parts of translation are initiation,
elongation, and termination.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 33 RNA
Protein Synthesis in Ribosome
hVp://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/Exam%201%20Review/
Ch02%20Nucleic%20Acids%20and%20ATP.htm 34 Initiation
RNA
• Initiation begins with
mRNA binding to the
ribosome.
• A tRNA brings the
first amino acid,
always at codon AUG.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 35 RNA
Elongation
• Elongation proceeds as the next tRNA molecule
delivers the next amino acid, and a peptide bond
forms between the two amino acids.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 36 RNA
Termination
• Translation continues until a stop codon (UAA,
UAG, or UGA) is reached, which is called
termination; the completed protein is released.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 37 RNA
Translation & Protein Synthesis
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 38 Mutations
Definition
• A mutation is a change in the nucleotide sequence
in a molecule of DNA.
• Some mutations are random, while others are
caused by mutagens.
• A point mutation is the substitution of one
nucleotide for another.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 39 Mutations
Definition
• A deletion mutation occurs when one or more
nucleotides is/are lost from a DNA molecule.
• An insertion mutation occurs when one or more
nucleotides is/are added to a DNA molecule.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 40 Mutations
Definition
• A silent mutation has a negligible effect to the
organism, because the resulting amino acid is
identical.
The mutation has no effect.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 41 Mutations
Genetic Disease
• A mutation that produces a protein with one
different amino acid usually has a small to
moderate effect on the protein overall.
• Some proteins, such as hemoglobin, substitution
of just one amino acid can result in the fatal
disease sickle cell anemia.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 42 Mutations
Genetic Disease
• If a mutation causes a big change, like producing
a stop codon, the remainder of the protein will
not be synthesized, which can have catastrophic
results.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 43 Mutations
Genetic Disease
• When a mutation causes a protein deficiency
or defective protein synthesis and this mutation is
passed through generations, it is a genetic disease.
Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 44