Chapter 27 Nucleosides, Nucleotides, and Nucleic Acids I Irene Lee Case Western Reserve University Cleveland, OH ©2004, Prentice Hall Organic Chemistry.

Chapter 27

Nucleosides,Nucleotides,

and Nucleic Acids I

Irene LeeCase Western Reserve University

Cleveland, OH©2004, Prentice Hall

Organic Chemistry 4th Edition

Paula Yurkanis Bruice

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

The energy released from ATP hydrolysis is used to drivethe phosphorylation of D-gluose (coupled reactions)

ATP as a Chemical Energy Source

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

P

O

-O O-O P

O

O-O-

+ H2O P

O

-OO-

OH2

Pyrophosphate can be further hydrolyzed to phosphate

Why is the hydrolysis of a phosphoanhydride bond soexergonic?

1. Greater electrostatic repulsion in ATP

2. More solvation in the products

3. Greater resonance stabilization in the products

P

O

-O O-O P

O

O-

P

O

-OO-

P

O

-OO-

OH

+

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 hormonesand certain enzymes that regulate cellular function

The Nucleic Acids

Biosynthesis of DNAoccurs in the 5’ 3’direction

Complementary Base Pairing in DNA

The sugar–phosphate is on the outside, and the basesare 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 itsC-terminal endEach amino acid is specified by a three-base sequenceknown 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 arefound in DNA to be recognized as mistakes

DNA Sequencing

Laboratory Synthesis of DNA

OligonucleotideSynthesis with

Phosphoramidites

The amino groups of the bases must be protected

Removal of the Protecting Group by Ammonia

Utilization of H-phosphatemonomer to synthesize DNA strand

Hoogsteen Base Pairing