Deoxyribonucleotides

Deoxyribonucleotides are the nucleotide building blocks of DNA. Each deoxyribonucleotide consists of a deoxyribose sugar, a nitrogenous base (adenine, thymine, cytosine or guanine), and one to three phosphate groups. The term commonly refers to the monophosphate form (dNMP), diphosphate (dNDP), and triphosphate (dNTP) forms, with the dNTPs serving as substrates for DNA synthesis.

The sugar in deoxyribonucleotides is 2'-deoxyribose, which lacks a hydroxyl group at the 2' position compared with ribonucleotides. This structural difference distinguishes DNA from RNA. The phosphate group is attached at the 5' carbon of the sugar, and DNA polymerization occurs when a 3'-hydroxyl of the growing strand attacks the incoming dNTP's alpha-phosphate, forming a phosphodiester bond and releasing a pyrophosphate.

Four deoxyribonucle bases exist: adenine (dA), thymine (dT), cytosine (dC), and guanine (dG). In DNA, thymine replaces uracil, which is typical of RNA. The availability and balance of deoxyribonucleotides within the cell—especially the dNTP pools—are tightly regulated to ensure fidelity during replication and repair.

Biosynthesis of deoxyribonucleotides begins with ribonucleotides and involves ribonucleotide reductase, which converts ribonucleotides to their deoxy forms. These deoxyribonucleotides are then phosphorylated to dNMPs, dNDPs, and finally dNTPs, through salvage and de novo pathways. Abnormal dNTP levels can increase mutation risk and are targets for therapeutic agents in cancer and other diseases.