Chapter 32: Nucleotides: Structure & Function

Structurally, these molecules are composed of nitrogen-containing heterocycles—purines and pyrimidines—which naturally exist in specific amino and oxo tautomeric forms under physiological conditions. When these heterocyclic bases are linked to pentose sugars like D-ribose or 2-deoxy-D-ribose via N-glycosidic bonds, they form nucleosides, which primarily exist in the anti rather than the syn conformation due to structural constraints. The addition of phosphoryl groups through esterification transforms these into nucleotides, with nucleoside triphosphates like ATP possessing high group transfer potential used to drive biological work. Beyond energy, the sources emphasize the role of cyclic nucleotides, such as cAMP and cGMP, which act as critical secondary messengers in various hormonal and signal-related cellular events. Individual mononucleotides are joined by 3-prime to 5-prime phosphodiester bonds to create directional polynucleotide chains, with the presence of a 2-prime hydroxyl group in RNA making it significantly more susceptible to hydrolysis compared to the more stable DNA. The text also explores how specialized nucleotide derivatives contribute to the synthesis of glycogen and lipids, or function as essential components of many coenzymes. Furthermore, it is noted that while five primary bases dominate, trace amounts of modified structures like 5-methylcytosine and pseudouridine play roles in recognition and RNA stability. Finally, the biomedical importance of synthetic nucleotide analogs is discussed, noting their application in treating conditions like gout and cancer by inhibiting key metabolic enzymes or disrupting the synthesis of nucleic acids during cell division.