Nucleic Acids

Nucleic acids are the informational macromolecules of the cell — they store, transmit, and express genetic information. The two main types are DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).

1. Building Blocks: Nucleotides

Every nucleic acid is a polymer of nucleotides. Each nucleotide has three components:

Component	DNA	RNA
Nitrogenous base	A, G (purines); C, T (pyrimidines)	A, G (purines); C, U (pyrimidines)
Sugar	Deoxyribose (no 2'-OH)	Ribose (has 2'-OH)
Phosphate	1–3 phosphate groups	1–3 phosphate groups

Nucleoside = base + sugar (no phosphate) Nucleotide = nucleoside + phosphate(s) at the 5'-OH

Common abbreviations: ATP, GTP, CTP, UTP (RNA precursors); dATP, dGTP, dCTP, dTTP (DNA precursors). Diphosphates (DP) and monophosphates (MP) are also named accordingly (e.g., GDP, AMP).

Polynucleotide chain

Nucleotides are linked by 3'→5' phosphodiester bonds — the phosphate group bridges the 3'-carbon of one sugar and the 5'-carbon of the next, forming the backbone. The bases project outward and can interact with other bases or proteins.

Polynucleotide structure showing 5'→3' phosphodiester linkages

Fig. 11.1 — Structure of a polynucleotide. The backbone is sugar–phosphate; the bases project from it. — Basic Medical Biochemistry, 6e

2. DNA Structure

The Double Helix

Watson and Crick (1953) established that DNA is double-stranded — two antiparallel polynucleotide chains wound into a right-handed helix, held together by hydrogen bonds between complementary base pairs:

A pairs with T (2 hydrogen bonds)
G pairs with C (3 hydrogen bonds)

The strands are antiparallel: one runs 5'→3', the other runs 3'→5'. The bases are stacked inside the helix (hydrophobic stacking interactions stabilize the structure), while the phosphate-sugar backbone is on the outside.

Forms of DNA

Fig. 11.9 — Z, B, and A forms of DNA — Basic Medical Biochemistry, 6e

Form	Helix	Base pairs/turn	Rise/bp	Notes
B-DNA	Right-handed	10.4	3.4 Å	Predominant form in vivo
A-DNA	Right-handed	11	2.3 Å	Found in DNA–RNA hybrids; more compact
Z-DNA	Left-handed	11	3.8 Å	Phosphates zig-zag; transiently formed near transcription start sites

Denaturation and Renaturation

Alkali causes strand separation but does not break phosphodiester bonds in DNA (in RNA, the 2'-OH is activated → RNA is cleaved).
Heat also denatures DNA; the Tm (melting temperature) is the temperature at which 50% of the DNA is single-stranded.
On slow cooling, complementary strands re-anneal (hybridize) — this principle underlies PCR, Southern blotting, and many diagnostic molecular techniques.

3. RNA — Types and Functions

Transcription of a DNA gene produces a single-stranded RNA with the same sequence as the coding strand (with U replacing T).

Type	Function
mRNA (messenger RNA)	Carries the coding sequence (codons) from DNA to ribosomes for translation into protein. In eukaryotes: 5' cap + coding region + 3' poly(A) tail.
rRNA (ribosomal RNA)	Structural and catalytic component of ribosomes; has extensive internal base-pairing. Forms ribonucleoprotein particles that bind mRNA and tRNA during translation.
tRNA (transfer RNA)	Adaptor molecule that brings the correct amino acid to the ribosome. Has a cloverleaf secondary structure; contains the anticodon (trinucleotide complementary to the mRNA codon) and the amino acid attachment site.
snRNA/miRNA/siRNA	Regulatory and processing roles (splicing, gene silencing, etc.)

4. Central Dogma

DNA  →  (Transcription)  →  RNA  →  (Translation)  →  Protein

Replication: DNA → DNA (semi-conservative; DNA polymerase)
Transcription: DNA → RNA (RNA polymerase)
Translation: mRNA → Protein (ribosomes, tRNA, amino acids)

5. Key Chemical Differences: DNA vs. RNA

Feature	DNA	RNA
Sugar	2'-deoxyribose	Ribose
Bases	A, G, C, T	A, G, C, U
Strands	Double	Single (usually)
Stability	More stable (no 2'-OH)	Less stable (cleaved by alkali)
Location	Nucleus, mitochondria	Nucleus, cytoplasm
Function	Information storage	Information expression

6. Clinical Relevance

Nucleic acid tests (NATs): PCR and related amplification methods detect pathogen DNA/RNA for infectious disease diagnosis (e.g., HIV viral load, COVID-19 PCR, TB NAAT).
Intercalating drugs: Doxorubicin (adriamycin) slips between stacked base pairs, inhibiting DNA replication and transcription — used in lymphoma and other cancers. It preferentially affects rapidly dividing cells.
Nucleoside analog drugs: Antivirals (acyclovir, tenofovir) and chemotherapeutics (5-fluorouracil) are modified nucleotides that disrupt DNA/RNA synthesis.
Circulating nucleic acids: Free DNA and RNA in plasma are biomarkers for cancer (liquid biopsy), prenatal diagnosis (cell-free fetal DNA), and organ transplant rejection.

Sources: Basic Medical Biochemistry – A Clinical Approach, 6e (Lieberman & Marks), pp. 353–370; Henry's Clinical Diagnosis and Management by Laboratory Methods; Ganong's Review of Medical Physiology, 26e.

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