Nucleic Acids

Nucleic acids are the information-carrying molecules of cells. DNA (deoxyribonucleic acid) stores the genetic instructions for making proteins, while RNA (ribonucleic acid) plays several roles in translating those instructions into functional proteins. Both are polymers of nucleotides.

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Nucleotide Structure

Key Definition: A nucleotide is the monomer of a nucleic acid. It consists of three components: a pentose sugar, a nitrogenous base, and a phosphate group.

DNA Nucleotides

• Pentose sugar: deoxyribose (C₅H₁₀O₄ — one fewer oxygen atom than ribose, specifically at the 2ʹ carbon position).
• Nitrogenous bases: adenine (A), thymine (T), cytosine (C), guanine (G).
• Phosphate group: PO₄³⁻, attached to the 5ʹ carbon of the sugar.

RNA Nucleotides

• Pentose sugar: ribose (C₅H₁₀O₅).
• Nitrogenous bases: adenine (A), uracil (U), cytosine (C), guanine (G).
• Phosphate group: same as DNA.

Purine and Pyrimidine Bases

The bases are classified into two groups:

• Purines (two-ring structure): adenine and guanine.
• Pyrimidines (single-ring structure): cytosine, thymine (DNA only), and uracil (RNA only).

Exam Tip: A useful mnemonic — Pyrimidines have a "y" in their name (cytosine, thymine, uracil — well, you can remember uracil as the odd one out). Alternatively, remember: the pure gold ring is a double ring — purines have two rings.

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Phosphodiester Bonds and Polynucleotide Chains

Nucleotides join together by condensation reactions between the phosphate group of one nucleotide and the hydroxyl group on the 3ʹ carbon of the sugar of the next nucleotide, forming a phosphodiester bond (a covalent bond with a phosphate group linking two sugar molecules).

This creates a sugar–phosphate backbone with alternating sugar and phosphate groups. The nitrogenous bases project out from the backbone.

A polynucleotide chain has directionality:

• The 5ʹ end has a free phosphate group on the 5ʹ carbon of the terminal sugar.
• The 3ʹ end has a free hydroxyl group on the 3ʹ carbon of the terminal sugar.

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DNA Structure — The Double Helix

James Watson and Francis Crick proposed the double helix model of DNA in 1953, building on X-ray crystallography data from Rosalind Franklin and Maurice Wilkins, and Chargaff's rules about base composition.

Key Features

1. Two polynucleotide strands wind around each other to form a right-handed double helix.
2. The strands are antiparallel: one strand runs 5ʹ→3ʹ while the other runs 3ʹ→5ʹ.
3. The sugar–phosphate backbones are on the outside of the helix.
4. The nitrogenous bases point inward and are joined by hydrogen bonds following complementary base pairing rules:
   • Adenine (A) pairs with thymine (T) — held by two hydrogen bonds.
   • Guanine (G) pairs with cytosine (C) — held by three hydrogen bonds.
5. A purine always pairs with a pyrimidine, ensuring a constant width of the helix (approximately 2 nm).

Chargaff's Rules

Erwin Chargaff (1950) found that in any DNA molecule:

• The amount of adenine equals the amount of thymine ([A] = [T]).
• The amount of guanine equals the amount of cytosine ([G] = [C]).
• Therefore, [purines] = [pyrimidines].

These observations were crucial evidence supporting Watson and Crick's complementary base pairing model.

Stability of the Double Helix

• The large number of hydrogen bonds between base pairs provides cumulative stability.
• Hydrophobic stacking interactions between adjacent base pairs (perpendicular to the helix axis) also contribute to stability.
• The sugar–phosphate backbone (with its covalent phosphodiester bonds) provides structural strength.

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RNA Structure