Enzymatic synthesis of mono and dinucleoside polyphosphates

• Published in: Biochimica et biophysica acta Vol. 1810; no. 12; pp. 1195 - 1204
• Main Authors: Fraga, Hugo, Fontes, Rui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2011
• Subjects: Ap 4A; Artemia; cell membranes; Dinucleoside Phosphates - biosynthesis; Dinucleoside polyphosphate; enzyme activity; Enzyme synthesis; enzymes; membrane proteins; Mononucleoside polyphosphate; Nucleotidyltransferases - metabolism; p 4A; polyphosphates; Promiscuous activity; LysRS; Mononucleoside polyphosphate; (N)p nNs; dim; Ap 2Cp; E1; FHIT; p 4A; Ap 2CHClp 2A; ger; Ap 2CH 2p; far; ( Rp)Ap 4A[αS]; Ap 2CCl 2p; d(5-fluoro-U); Luc; p nN1; Dinucleoside polyphosphate; Ap 3CH 2pA; P n; Np nN; Ap 2C(OH)(CH 3)p; N1p nN2; AaaRS; NRPS; p nN; Ap 2CH 2p 2A; Ap 3thia; PPi; Promiscuous activity; arabino-A; MITF; Ap 4A[αS]; εA; Ap 2NHp 2A; Ap 4A[βS]; Enzyme synthesis; ( Sp)Ap 4A[αS]; ApCH 2p 3A; p nA; Gp 5G; JAR1; PGK; Ap 4A; AZT; MURD; AARS
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2011.09.010

Mono and dinucleoside polyphosphates (p nNs and Np nNs) 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. 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 nNs (and/or p nN), it is not clear which ones are responsible for their in vivo accumulation. Despite the large amount of knowledge already available, important questions remain to be answered and a more complete understanding of p nNs and Np nNs synthesis mechanisms is required. With the possible exception of (GTP:GTP guanylyltransferase of Artemia), all enzymes able to catalyse the synthesis of p nNs and Np nNs are unspecific and the factors that can promote their synthesis relative to the canonical enzyme activities are unclear. The fact that p nNs and Np nNs 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. ► The synthesis of mono and dinucleoside polyphosphates (p nNs and Np nNs) was reviewed. ► So far only GTP:GTP guanylyltransferase catalyses Np nNs synthesis in a specific way. ► In all the other enzymes (N)p nNs synthesis results from promiscuous activities. ► The significance of these promiscuous activities is discussed.