Transcript Lecture Resource ()

Organic Chemistry
4th Edition
Paula Yurkanis Bruice
Chapter 27
Nucleosides,
Nucleotides,
and
Nucleic Acids I
Irene Lee
Case Western Reserve University
Cleveland, OH
©2004, Prentice Hall
Nucleic Acids
In nucleic acid, the phosphate group is phosphodiester
The Bases in Nucleic Acids
Adenine, guanine, cytosine, and thymine are found in
DNA
Adenine, guanine, cytosine, and uracil are found in RNA
Nucleosides = Base + Sugar
Nucleotides = Base + Sugar +
Phosphate
Different Forms of Nucleotides
ATP as a Chemical Energy Source
The energy released from ATP hydrolysis is used to drive
the phosphorylation of D-gluose (coupled reactions)
Breakage of the Phosphoanhydride
Bond in ATP
Without ATP, the OH– group cannot be displaced
This reaction does not occur without ATP because of the
poor leaving group
Phosphoryl Transfer Reaction
Mechanism I
Phosphoryl Transfer Reaction
Mechanism II
Phosphoryl Transfer Mechanism III
Pyrophosphate can be further hydrolyzed to phosphate
O
O
P
P OO
-O OO-
+ H2O
O
2 -O P OH
O-
Why is the hydrolysis of a phosphoanhydride bond so
exergonic?
1. Greater electrostatic repulsion in ATP
2. More solvation in the products
3. Greater resonance stabilization in the products
O
O
P
P
O
-O OO-
O
P
-O
O-
O
+
P
-O
OH
O-
The interactions between ATP, Mg2+, and arginine and
lysine residues at the active site of an enzyme
Since all the negative charges in ATP are neutralized,
ATP is readily approached by nucleophiles
Other Important Nucleotides
Cyclic AMP serves as a link between several hormones
and certain enzymes that regulate cellular function
The Nucleic Acids
Biosynthesis of DNA
occurs in the 5’
3’
direction
Complementary Base Pairing in DNA
The sugar–phosphate is on the outside, and the bases
are on the inside
The DNA Double Helix
Hydrolysis of RNA
The Three Helical Forms of DNA
Hydrogen bonding and base stacking interactions hold
the DNA helix together
Replication of DNA
Transcription of DNA
• A stretch of bases representing a portion of a gene is
called an exon
• A stretch of bases that contain no genetic information is
called an intron
• mRNA is spliced prior to leaving the nucleus
A Transfer RNA
The Proposed Mechanism for
Aminoacyl-tRNA Synthetase
The Substrate-Binding Site for tRNAHis
A protein is synthesized from its N-terminal end to its
C-terminal end
Each amino acid is specified by a three-base sequence
known as the genetic code
Translation
Why does DNA contain thymine instead of uracil?
The synthesis of thymine is energetically expensive
Because cytosine can be converted to uracil ….
Having T’s in place of U’s in DNA allows the U’s that are
found in DNA to be recognized as mistakes
DNA Sequencing
Laboratory Synthesis of DNA
Oligonucleotide
Synthesis with
Phosphoramidites
The amino groups of the bases must be protected
Removal of the Protecting Group by
Ammonia
Utilization of H-phosphate
monomer to synthesize
DNA strand
Hoogsteen Base Pairing