Phosphoryl Group Transfers and ATP:-Inorganic Polyphosphate Is a Potential Phosphoryl Group Donor
Inorganic polyphosphate (polyP) is a linear polymer composed of many tens or hundreds of Pi residues linked through phosphoanhydride bonds. This polymer, present in all organisms, may accumulate to high levels in some cells. In yeast, for example, the amount of polyP that accumulates in the vacuoles would represent, if dis tributed uniformly throughout the cell, a concentration of 200 mM.
One potential role for polyP is to serve as a phosphagen, a reservoir of phosphoryl groups that can be used to generate ATP, as creatine phosphate is used in muscle. PolyP has about the same phosphoryl group transfer potential as PPi. The shortest polyphosphate, PPi (n 2), can serve as the energy source for active transport of H in plant vacuoles. For at least one form of the enzyme phosphofructokinase in plants, PPi is the phosphoryl group donor, a role played by ATP in animals and microbes (p. XXX). The finding of high concentrations of polyP in volcanic condensates and steam vents suggests that it could have served as an energy source in prebiotic and early cellular evolution. In prokaryotes, the enzyme polyphosphate ki nase-1 (PPK-1) catalyzes the reversible reaction
by a mechanism involving an enzyme-bound phospho histidine intermediate (recall the mechanism of nucleoside diphosphate kinase, described above). A second enzyme, polyphosphate kinase-2 (PPK-2), catalyzes the reversible synthesis of GTP (or ATP) from poly phosphate and GDP (or ADP):
PPK-2 is believed to act primarily in the direction of GTP and ATP synthesis, and PPK-1 in the direction of polyphosphate synthesis. PPK-1 and PPK-2 are present in a wide variety of prokaryotes, including many pathogenic bacteria. In prokaryotes, elevated levels of polyP have been shown to promote expression of a number of genes in volved in adaptation of the organism to conditions of starvation or other threats to survival. In Escherichia coli, for example, polyP accumulates when cells are starved for amino acids or Pi, and this accumulation confers a survival advantage. Deletion of the genes for polyphosphate kinases diminishes the ability of certain pathogenic bacteria to invade animal tissues. The en zymes may therefore prove to be vulnerable targets in the development of new antimicrobial drugs. No gene in yeast encodes a PPK-like protein, but four genes—unrelated to bacterial PPK genes—are necessary for the synthesis of polyphosphate. The mechanism for polyphosphate synthesis in eukaryotes seems to be quite different from that in prokaryotes.
