Nucleotides are organic molecules that serve as the monomers, or subunits, of nucleic acids like DNA
and RNA. While a nucleoside is a nucleobase linked to a sugar,
a nucleotide is composed of a nucleoside and one or more phosphate groups. Thus,
nucleosides can be phosphorylated by specific kinases in the cell on the sugar’s primary
alcohol group (-CH2-OH) to produce nucleotides. In a word, the term "nucleotide" generally refers to a
nucleoside monophosphate, but a nucleoside diphosphate or nucleoside
triphosphate could be considered a nucleotide as well.
can be synthesized by a variety of means both in
vitro and in vivo.
can be synthesized de novo or recycled through salvage pathways. The components
used in de novo nucleotide synthesis are derived from biosynthetic precursors
of carbohydrate and amino acid metabolism, and from ammonia and
carbon dioxide. The liver is the major organ of de novo synthesis of all four
nucleotides. De novo synthesis of pyrimidines and purines follows two different
pathways. Pyrimidines are synthesized first from aspartate and
carbamoyl-phosphate in the cytoplasm to the common precursor ring structure
orotic acid, onto which a phosphorylated ribosyl unit is covalently linked.
Purines, however, are first synthesized from the sugar template onto which the
ring synthesis occurs. For reference, the syntheses of
the purine and pyrimidine nucleotides are carried out by
several enzymes in the cytoplasm of the cell, not within a
specific organelle. Nucleotides undergo breakdown such that useful parts
can be reused in synthesis reactions to create new nucleotides.
vitro, protecting groups may be used during laboratory production of
nucleotides. A purified nucleoside is protected to create
a phosphoramidite, which can then be used to obtain analogues not found in
nature and/or to synthesize an oligonucleotide.
Nucleosides can be produced by de novo synthesis pathways.
In particular in the liver, but they are more abundantly
supplied via ingestion and digestion of nucleic acids in the diet, whereby nucleotidases break down nucleotides (such as the thymidine monophosphate) into nucleosides (such as thymidine) and phosphate.
In medicine, several nucleoside
analogues are used as antiviral
or anticancer agents. In molecular biology, several analogues of the sugar backbone exist.