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NucleosideEdit

Nucleosides are fundamental building blocks of life’s informational molecules, formed when a nitrogen-containing base is attached to a five-carbon sugar. In most living systems, the sugar is either ribose (as in RNA) or deoxyribose (as in DNA), and the base can be one of two broad families: purines (such as adenine and guanine) or pyrimidines (such as cytosine, thymine, and uracil). When a phosphate group is added to a nucleoside, the result is a nucleotide, which serves as the direct substrate for DNA and RNA synthesis and for energy transfer in the cell. Nucleosides thus sit at the crossroads of information storage, metabolism, and signaling.

The essential structural feature is the beta-N-glycosidic bond that links the sugar to the base. In detail, the bond connects the anomeric carbon of the sugar (C1' in the sugar ring) to a nitrogen atom in the base (N9 in purines, N1 in pyrimidines). The sugar portion is typically described as beta-D-ribofuranose for RNA or beta-D-2′-deoxyribofuranose for DNA. These choices—ribose versus deoxyribose, and the purine versus pyrimidine bases—shape the behavior of nucleosides in polymers, signaling, and metabolism. See beta-D-ribofuranose and glycosidic bond for more detail.

Definition and structure

  • A nucleoside equals a base plus a sugar, with no phosphate. The base may be a purine (adenine, guanine, hypoxanthine, xanthine, etc.) or a pyrimidine (cytosine, thymine, uracil, etc.). See purine and pyrimidine for overview.
  • The sugar is a five-carbon ring, most commonly ribose in RNA and deoxyribose in DNA. The specific form of the sugar influences whether the nucleoside participates in RNA or DNA chemistry. See ribose and deoxyribose.
  • The naming convention reflects the base; for example, the nucleoside formed from adenine is called adenosine, from guanine is guanosine, from cytosine is cytidine, from thymine is thymidine (the deoxyribonucleoside), and from uracil is uridine.
  • Modified nucleosides exist in biology, especially in tRNA, where a variety of alterations fine-tune decoding and stability. See pseudouridine and inosine for notable examples.

Varieties and examples

  • Purine nucleosides: adenosine, guanosine, and inosine are the principal representatives in biology. Purine nucleosides contribute to cellular signaling and energy-related processes once they are converted to nucleotides.
  • Pyrimidine nucleosides: cytidine (RNA form), uridine (RNA form), and the deoxynucleoside thymidine (DNA form) are the core pyrimidine nucleosides. The deoxyribonucleoside thymidine is sometimes referred to as deoxythymidine.
  • Modified nucleosides: cells also generate unusual nucleosides such as pseudouridine in RNA, which can affect structure and function.

Biosynthesis and metabolism

  • Nucleosides arise in cells through two broad routes: salvage pathways, which reuse existing bases and sugars, and de novo synthesis, which assembles them anew. See nucleotide salvage and de novo synthesis for context.
  • The conversion of nucleosides to nucleotides is accomplished by kinases that add phosphate groups. This phosphorylation activates nucleosides for incorporation into nucleic acids or for roles in signaling and metabolism.
  • Enzymes such as adenosine kinase and nucleoside phosphorylase participate in the interconversion of nucleosides and nucleotides, balancing supply in response to cellular demand.

Functions and significance

  • As precursors to nucleotides, nucleosides are essential for DNA replication and RNA transcription. They provide the chemical scaffolds that genetic information uses to be stored and read.
  • Adenosine, one of the best-known nucleosides, also functions as a local signaling molecule in tissues, affecting vascular tone, neurotransmission, and inflammation. See adenosine for more.
  • Nucleosides can be pharmacologically active. Several antiviral and anticancer drugs are nucleoside analogs, designed to disrupt nucleic acid synthesis in diseased cells or viruses. Examples include acyclovir (used against herpesviruses) and several drugs like zidovudine and lamivudine that target viral replication by mimicking natural nucleosides but terminating DNA synthesis or hindering polymerases. See acyclovir, zidovudine, and lamivudine.

Medical and pharmacological relevance

  • Nucleoside analogs are powerful tools in medicine when properly activated by cellular or viral kinases. Their action often hinges on misincorporation into viral or cancerous DNA or RNA, followed by chain termination or faulty replication.
  • A key design principle for these drugs is selectivity: many analogs exploit differences between host and pathogen enzymes to minimize damage to normal cells. The activity, toxicity, and resistance profiles of nucleoside drugs are active areas of clinical research and policy discussions about drug pricing and accessibility.
  • Resistance can arise when pathogens alter kinases or polymerases so that the drug is no longer efficiently activated or incorporated. This is a common challenge in antiviral therapy and cancer treatment, prompting ongoing development of second- and third-generation nucleoside analogs.

See also