Nucleotides
🧬 Nucleotides are the essential building blocks of nucleic acids (DNA & RNA).
They serve not only in genetic information storage, but also in energy metabolism, cellular signalling, and enzymatic reactions.
Their balanced synthesis and breakdown are critical for normal cell function; disruption leads to major diseases.
🔑 Structure of Nucleotides
- Nitrogenous Base 🧾 :
- Pyrimidines → Cytosine (C), Thymine (T, DNA), Uracil (U, RNA).
- Purines → Adenine (A), Guanine (G).
- Pentose Sugar 🍬 :
- Deoxyribose → DNA nucleotides.
- Ribose → RNA nucleotides.
- Phosphate Group 🔋 :
- One, two, or three phosphate groups attached at the 5′ carbon → AMP, ADP, ATP.
📂 Types of Nucleotides
- DNA Nucleotides 🧬 :
- A, G, C, T with deoxyribose + phosphate.
- RNA Nucleotides 🧾 :
- A, G, C, U with ribose + phosphate.
⚙️ Functions of Nucleotides
- Genetic Information 🧾 :
- Form DNA & RNA → storage and transfer of genetic code.
- Energy Transfer ⚡ :
- ATP → universal energy currency. GTP → protein synthesis & signalling.
- Cell Signalling 📡 :
- cAMP & cGMP → key second messengers in hormonal pathways (e.g., adrenaline, nitric oxide).
- Enzyme Cofactors 🧪 :
- NAD⁺, FAD, CoA → essential in metabolism & redox reactions.
🔄 Nucleotide Metabolism
- De Novo Synthesis 🏭 :
- Pyrimidines & purines synthesised from amino acids, CO₂, folate derivatives. Targeted by chemotherapy (e.g., methotrexate, 5-FU).
- Salvage Pathway ♻️ :
- Recycling of bases/nucleosides (important in rapidly dividing cells). HGPRT is key enzyme (defective in Lesch–Nyhan).
- Catabolism 🧹 :
- Pyrimidines → soluble metabolites.
- Purines → uric acid (overproduction → gout, urate kidney stones).
🧾 Clinical Relevance
- Genetic Disorders 🧬 :
- Lesch–Nyhan syndrome (HGPRT deficiency) → hyperuricaemia, gout, neurological dysfunction, self-mutilation.
- ADA deficiency → impaired lymphocyte function → severe combined immunodeficiency (SCID).
- Cancer 🎗️ :
- Cancer cells ↑ nucleotide synthesis → targeted by antimetabolites (methotrexate, 5-FU, hydroxyurea).
- Viral Infections 🦠 :
- Antiviral nucleoside/nucleotide analogues (acyclovir, zidovudine, remdesivir) block viral polymerases.
- Gout 💥 :
- Hyperuricaemia from excess purine catabolism. Managed with xanthine oxidase inhibitors (allopurinol, febuxostat).
📚 Summary
Nucleotides = base + sugar + phosphate.
They are essential for genetic coding, metabolism, and cell signalling.
Metabolism involves de novo synthesis, salvage, and catabolism.
Disorders range from inborn errors (Lesch–Nyhan, SCID) to acquired diseases (gout, cancer, viral infections).
Therapeutics often target nucleotide metabolism → chemotherapy, antivirals, gout treatment.
