CHE 203: Chemistry of Biomolecules

Study Notes

Nucleotides have various roles in cellular metabolism:
- Energy currency in metabolic reactions (e.g., ATP)
- Coenzyme part for various enzymes and metabolic intermediates (e.g., NAD+, NADP+)
- Constituents of nucleic acids: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)
Nucleotides contain three components:
1. Nitrogen-containing base
2. Pentose (five-carbon sugar)
3. One or more phosphates

Nitrogenous bases are derivatives of pyrimidine and purine
Major bases of nucleic acids:
- Adenine (A)
- Guanine (G)
- Cytosine (C)
- Thymine (T)
- Uracil (U) (only in RNA)
Minor bases of many types occur in tRNAs, often methylated forms of the major bases

Names of nucleosides and nucleotides containing the five common bases are listed
Examples of adenosine monophosphates (AMP, ADP, ATP)

RNA is hydrolyzed rapidly under alkaline conditions, but DNA is not
The 2’-hydroxyl group in the ribose moieties of RNA is directly involved in this reaction

Watson-Crick model for the structure of double-helical DNA
Two antiparallel chains of DNA are wound around the same axis
Hydrophilic backbones of alternating deoxyribose and phosphate groups are on the outside of the helix
Purine and pyrimidine bases of both strands are stacked inside the double helix
Base stacking accounts for the 3.4 Å repeat along the length of the helix

Begins with a partial unwinding of the double helix, exposing the recognition site on the bases
Activated forms of the complementary nucleotides (A with T and G with C) associate
Two new strands begin to grow
Addition takes place 5′ → 3′, catalyzed by DNA polymerase
Each nucleotide is joined as a 5′-nucleoside triphosphate that adds a nucleotide to the free 3′-hydroxyl group of the growing chain

RNA contains ribose rather than deoxyribose and uracil rather than thymine
Three major kinds of RNA:
1. Messenger RNA (mRNA)
2. Ribosomal RNA (rRNA)
3. Transfer RNA (tRNA)
Each type of RNA serves a specific function
RNA molecules are much smaller than DNA and are usually single-stranded

RNA directs biosynthesis of peptides and proteins, which is catalyzed by mRNA in ribosomes
The ribonucleotide sequence in mRNA forms a message that determines the order in which different amino acid residues are to be joined
Codons are sequences of three ribonucleotides that specify a particular amino acid
tRNA has a segment called an anticodon, a sequence of three ribonucleotides complementary to the codon sequence
Amino acids are brought to the ribosomes, where they are joined to form a protein

The Maxam-Gilbert method uses organic chemistry to cleave phosphate linkages at specific bases
The Sanger dideoxy method uses enzymatic reactions to synthesize DNA fragments with fluorescent labels
The Sanger method is widely used and automated, even in genome sequencing

Copies DNA molecules by unwinding the double helix and copying each strand using enzymes
The new double helices are unwound and copied again, exponentially amplifying the target DNA sequence