Polyphosphate as donor of high-energy phosphate for the synthesis of ADP and ATP

Abstract

Here, we studied the potential role of inorganic polyphosphate (polyP) as an energy source for ADP and ATP formation in the extracellular space. In SaOS-2 cells, we show that matrix vesicles are released into the extracellular space after incubation with polyP. These vesicles contain both alkaline phosphatase (ALP) and adenylate kinase (AK) activities (mediated by ALPL and AK1 enzymes). Both enzymes translocate to the cell membrane in response to polyP. To distinguish the process(es) of AMP and ADP formation during ALP hydrolysis from the ATP generated via the AK reaction, inhibition studies with the AK inhibitor A(5')P5(5')A were performed. We found that ADP formation in the extracellular space occurs after enzymatic ATP synthesis. After exposure to polyP, a significant increase of the ADP level was observed, which is likely to be been catalyzed by ALP. This increase is not due to an intensified ATP release via exocytosis. The ATP level in the extracellular space of SaOS-2 cells is strongly increased in response to polyP, very likely mediated by the AK. We propose that the ALP and AK enzymes are involved in the extracellular ADP and ATP synthesis.

In Situ Polyphosphate Nanoparticle Formation in Hybrid Poly(vinyl alcohol)/Karaya Gum Hydrogels: A Porous Scaffold Inducing Infiltration of Mesenchymal Stem Cells

“…[9,13] Within the cells polyP is stored in vesicles, termed acidocalcisomes. [9,13] Within the cells polyP is stored in vesicles, termed acidocalcisomes.…”

“…[20] The polyP is prone to enzymatic hydrolysis with the alkaline phosphatase (ALP), the dominant intra-and extracellular enzyme that hydrolyzes the phosphoanhydride bonds which link the phosphate groups. [9,13] Most interesting is the fact that the amorphous polyP nanoparticles meet the prerequisites of being fully biocompatible and provided with comprehensive functionalities allowing tissue incorporation and initiating tissue regeneration (ref. [22] In turn, the extracellularly formed ADP undergoes enzymatic disproportionation to adenosine 5′-monophosphate (AMP) and ATP, catalyzed by the adenylate kinase.…”

Critical and diverse roles of phosphates in human bone formation

“…Indeed, polyP has been shown to increase extracellular ATP and ADP generation in SaOS-2 (osteoblast-like) cells. 131 In the same cell type, polyP was shown to promote proliferation and mineralisation under hypoxic conditions, those found in physiological and ectopic bone formation sites. 132 This suggests that polyP can act as an alternative phosphate and metabolic energy source, particularly in extracellular or hypoxic conditions, such as those in bone formation where ATP is not readily available.…”

Collagen‐inducing biologization of prosthetic material for hernia repair: Polypropylene meshes coated with polyP/collagen

“…We disclosed that polyP in the extracellular space undergoes enzymatic hydrolysis via the alkaline phosphatase (ALP) . During this reaction the energy‐rich phosphoric anhydride bonds is cleaved and the free energy (ΔG) is released which is subsequently stored in ADP and ATP via the enzyme adenylate kinase . Subsequently, the available metabolic fuel is ready for channeling into energy‐requiring processes, like chaperon‐mediated protein folding.…”

“…19 During this reaction the energy-rich phosphoric anhydride bonds is cleaved and the free energy (DG) is released which is subsequently stored in ADP and ATP via the enzyme adenylate kinase. 20 Subsequently, the available metabolic fuel is ready for channeling into energy-requiring processes, like chaperonmediated protein folding. The physiological polymer polyP, also if packed into nanoparticles, is highly bio-available since it is prone to the ALP enzyme 21 and in turn can activate the gene expression of cells, as reported.…”