Enzymes of Inorganic Polyphosphate Metabolism

Abstract

Inorganic polyphosphate (PolyP) is a linear polymer containing a few to several hundred orthophosphate residues linked by energy-rich phosphoanhydride bonds. Investigation of PolyP-metabolizing enzymes is important for medicine, because PolyPs perform numerous functions in the cells. In human organism, PolyPs are involved in the regulation of Ca(2+) uptake in mitochondria, bone tissue development, and blood coagulation. The essentiality of polyphosphate kinases in the virulence of pathogenic bacteria is a basis for the discovery of new antibiotics. The properties of the major enzymes of PolyP metabolism, first of all polyphosphate kinases and exopolyphosphatases, are described in the review. The main differences between the enzymes of PolyP biosynthesis and utilization of prokaryotic and eukaryotic cells, as well as the multiple functions of some enzymes of PolyP metabolism, are considered.

Role of β-hydroxybutyrate, its polymer poly-β-hydroxybutyrate and inorganic polyphosphate in mammalian health and disease

“…In mammalians, a long-chain endopolyphosphatase was purified from rat and bovine brain (Kumble and Kornberg, 1996), a human metastasis regulator protein H-prune was identified as a short-chain specific exopolyphosphatase (Tammenkoski et al, 2008), and mammalian intestinal alkaline phosphatase was characterized as a very active exopolyphosphatase (Lorenz and Schroder, 2001). In addition, 41% homology has been found between yeast exopolyphosphatase PP1 gene product and human acid sphingomyelinase-like phosphodiesterase (Duan, 2006; Kulakovskaya and Kulaev, 2013). In the colon, this enzyme may play anti-proliferative and anti-inflammatory roles via ceramide generation, reducing the lysophosphatidic acid formation, and inactivating the platelet-activating factor and mutations in its gene have been found in cancer cells of the intestines (Duan, 2006).…”

“…In the colon, this enzyme may play anti-proliferative and anti-inflammatory roles via ceramide generation, reducing the lysophosphatidic acid formation, and inactivating the platelet-activating factor and mutations in its gene have been found in cancer cells of the intestines (Duan, 2006). Interestingly, the human protein H-prune exhibits 91% homology with the sequences of yeast exopolyphosphatase PPX1 (Kulakovskaya and Kulaev, 2013). Furthermore, in some prokaryotes [such as Micrococcus luteus, Corynebacterium ammoniagenes (Fillipovich et al, 2000), Micrococcus flavus and Mycobacterium tuberculosis (Kawai et al, 2000)] NAD kinase catalyzes phosphorylation of NAD using both ATP and polyP as phosphoryl donors (Figure 3B) while E. Coli NAD kinase is not able to use polyP (Kawai et al, 2001).…”

Inorganic pyrophosphatase from the red flour beetle (Tribolium castaneum) modulates mitochondrial polyphosphate metabolism

“…One of the main functions of polyP is to act as a Pi reserve in both prokaryotes and in unicellular eukaryotes (Rao, Gomez‐Garcia, & Kornberg, ). However, high eukaryotes display lower amounts of cellular polyP and these polymers act presumably as regulators of energy and phosphorus metabolism (T. Kulakovskaya & Kulaev, ). Since the Pi levels are in opposite with the polyP levels, our results suggested that polyP was involved in the mitochondrial bioenergetics of T. castaneum .…”

“…PPXs have been best studied in S. cerevisiae ; after subfractionation of its mitochondria, it was revealed that both the membrane preparation and the soluble fraction possessed exopolyphosphatase activities in equal proportions (T. Kulakovskaya & Kulaev, ). In T. castaneum, mitochondrial subfractionation revealed membrane and soluble PPXs, as reported in yeast; however, most activities were determined in the soluble fraction (T. Kulakovskaya & Kulaev, ).…”

“…PPXs are enzymes characterized as displaying an affinity for high‐molecular‐weight polyP, (T. Kulakovskaya & Kulaev, ). However, PPX1 of S. cerevisiae and Leishmania major is more active in hydrolyzing short‐chain polyPs, such as polyP 3 (Lichko, Kulakovskaya, & Kulaev, ; Rodrigues, Ruiz, Vieira, Hill, & Docampo, ).…”