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 Gp
4G, Gp
3G, and various Np
3-4Gs. The adenylated counterparts, such as Ap
3A and Ap
4A, are synthesized by ligases, at least by some aminoacyl-tRNA synthetases. Ap
4A phosphorylase, firefly luciferase, acyl-CoA synthetase, and the DNA- and RNA-ligases are also able to produce Np
3-6As. 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 Np
3-6N's. These are the Np
3N′ hydrolases, the asymmetrically and symmetrically acting Np
4N′ hydrolases, the Np
nN′ phosphorylases, and recently described hydrolases that prefer Ap
6A and Ap
5A as substrates. Human Fhit protein, a putative tumor suppressor, behaves as a typical Np
3N′ hydrolase and is a member of the HIT (histidine triad) protein family. The human Np
4N′ hydrolase belongs to the MutT motif or Nudix (nucleoside diphosphate attached to “x”) hydrolase protein family. The level of Np
3-6N's in the cells increases dramatically under stress. It is suggested that these minor nucleotides act as both intra- and extracellular signalling molecules. Ap
nAs interact with purine receptors and affect vascular tone. Chemically synthesized analogues of Np
nN's help us to understand the mechanism of action of the enzymes mentioned, and some of them are candidates for drugs.
抄録全体を表示