Enzymatic synthesis of mono and dinucleoside polyphosphates

Background: Mono and dinucleoside polyphosphates (p(n)Ns and Np(n)Ns) exist in living organisms and induce diverse biological effects through interaction with intracellular and cytoplasmic membrane proteins. The source of these compounds is associated with secondary activities of a diverse group of enzymes.

Scope of review: Here we discuss the mechanisms that can promote their synthesis at a molecular level. Although all the enzymes described in this review are able to catalyse the in vitro synthesis of Np(n)Ns (and/or p(n)N), it is not clear which ones are responsible for their in vivo accumulation.

Major conclusions: Despite the large amount of knowledge already available, important questions remain to be answered and a more complete understanding of p(n)Ns and Np(n)Ns synthesis mechanisms is required. With the possible exception of (GTP:GTP guanylyltransferase of Artemia), all enzymes able to catalyse the synthesis of p(n)Ns and Np(n)Ns are unspecific and the factors that can promote their synthesis relative to the canonical enzyme activities are unclear.

General significance: The fact that p(n)Ns and Np(n)Ns syntheses are promiscuous activities of housekeeping enzymes does not reduce its physiological or pathological importance. Here we resume the current knowledge regarding their enzymatic synthesis and point the open questions on the field.