nucleoside

Nucleosides consist of a nitrogenous base (adenine, guanine, cytosine, thymine, or uracil) attached to a five-carbon sugar (ribose in RNA nucleosides, deoxyribose in DNA nucleosides) via a β-N-glycosidic bond at the 1' carbon of the sugar. When a phosphate group (or groups) is added to the 5' carbon of the sugar, the nucleoside becomes a nucleotide (e.g., adenosine + phosphate = AMP). Common nucleosides include adenosine, guanosine, cytidine, thymidine, and uridine.

Clinically, nucleoside analogs are a major drug class exploited in antiviral and anticancer therapy because they mimic natural nucleosides but disrupt DNA/RNA synthesis. Examples include: - Nucleoside reverse transcriptase inhibitors (NRTIs) for HIV: zidovudine (AZT), lamivudine, tenofovir (technically a nucleotide analog), abacavir — these lack a 3'-OH group, causing chain termination during reverse transcription. - Antiviral agents: acyclovir (guanosine analog) for HSV/VZV, ribavirin for HCV/RSV. - Chemotherapeutic agents: cytarabine (cytidine analog) for AML, gemcitabine for solid tumors, 5-fluorouracil (pyrimidine analog) for colorectal cancer.

Metabolically, nucleosides are generated via salvage pathways (recycling free bases) or de novo synthesis. Nucleoside diphosphate kinase and other enzymes interconvert nucleoside mono-, di-, and triphosphates. Deficiencies in nucleoside/nucleotide metabolism enzymes (e.g., adenosine deaminase deficiency causing SCID, or HGPRT deficiency causing Lesch-Nyhan syndrome) are classic board topics illustrating the clinical importance of these pathways.

Key distinction for exams: Nucleoside = base + sugar (no phosphate). Nucleotide = base + sugar + phosphate. This distinction is frequently tested in biochemistry and pharmacology questions.