Abstract
Dinucleoside 5′, 5′′′-Pα, Pω-polyphosphates have been found in all cells examined. So far, the only known specific enzyme that catalyzes the synthesis of these polyphosphates is GTP:GTP guanylyltransferase. This enzyme produces Gp4G, Gp3G, and various Np3-4Gs. The adenylated counterparts, such as Ap3A and Ap4A, are synthesized by ligases, at least by some aminoacyl-tRNA synthetases. Ap4A phosphorylase, firefly luciferase, acyl-CoA synthetase, and the DNA- and RNA-ligases are also able to produce Np3-6As. By contrast, in addition to nonspecific enzymes such as phosphodiesterase I and nucleotide pyrophosphatase, there occur in all types of organism specific enzymes that degrade Np3-6N's. These are the Np3N′ hydrolases, the asymmetrically and symmetrically acting Np4N′ hydrolases, the NpnN′ phosphorylases, and recently described hydrolases that prefer Ap6A and Ap5A as substrates. Human Fhit protein, a putative tumor suppressor, behaves as a typical Np3N′ hydrolase and is a member of the HIT (histidine triad) protein family. The human Np4N′ hydrolase belongs to the MutT motif or Nudix (nucleoside diphosphate attached to “x”) hydrolase protein family. The level of Np3-6N's in the cells increases dramatically under stress. It is suggested that these minor nucleotides act as both intra- and extracellular signalling molecules. ApnAs interact with purine receptors and affect vascular tone. Chemically synthesized analogues of NpnN's help us to understand the mechanism of action of the enzymes mentioned, and some of them are candidates for drugs.
