Nucleic Acid Structure

nucleoside versus nucleotide

/ NEW-klee-oh-side / NEW-klee-oh-tide /

Two words sit one letter apart and trip up nearly every beginner: nucleoside and nucleotide. They name almost the same thing, and the difference is a single piece — the phosphate.

A nucleoside is just a base joined to a sugar: two of the three parts, no phosphate. A nucleotide is a nucleoside that has gained one or more phosphate groups: all three parts. The simple memory hook is that nucleotide has a 't', and so does the word phosphate — the 't' word is the one with the phosphate. So adenosine is a nucleoside; adenosine monophosphate (AMP) is a nucleotide; add two more phosphates and you reach ATP, still a nucleotide.

The distinction is not pedantry. Only nucleotides, with their charged phosphates, can be linked into a DNA or RNA strand, because it is the phosphate that forms the bond to the next sugar. Many antiviral and anticancer drugs are nucleoside analogues — fake bases-plus-sugars that the cell mistakes for the real thing and tries to add to a growing strand, jamming the machinery.

The drug acyclovir, used against herpes, is a nucleoside analogue: it is a guanine-like base on a stripped-down sugar with no phosphate, which the infected cell phosphorylates and then mistakenly inserts into viral DNA, stopping it dead.

Nucleoside + phosphate = nucleotide; the 't' word carries the phosphate.

Do not assume a nucleotide has exactly one phosphate. AMP, ADP, and ATP are all nucleotides — one, two, and three phosphates respectively. The defining feature is having at least one phosphate, not a particular number.

Also called
nucleoside核苷