Polyphosphate as a metabolic fuel in Metazoa: A foundational breakthrough invention for biomedical applications

Abstract

In animals, energy-rich molecules like ATP are generated in the intracellular compartment from metabolites, e.g. glucose, taken up by the cells. Recent results revealed that inorganic polyphosphates (polyP) can provide an extracellular system for energy transport and delivery. These polymers of multiple phosphate units, linked by high-energy phosphoanhydride bonds, use blood platelets as transport vehicles to reach their target cells. In this review it is outlined how polyP affects cell metabolism. It is discussed that polyP influences cell activity in a dual way: (i) as a metabolic fuel transferring metabolic energy through the extracellular space; and (ii) as a signaling molecule that amplifies energy/ATP production in mitochondria. Several metabolic pathways are triggered by polyP, among them biomineralization/hydroxyapatite formation onto bone cells. The accumulation of polyP in the platelets allows long-distance transport of the polymer in the extracellular space. The discovery of polyP as metabolic fuel and signaling molecule initiated the development of novel techniques for encapsulation of polyP into nanoparticles. They facilitate cellular uptake of the polymer by receptor-mediated endocytosis and allow the development of novel strategies for therapy of metabolic diseases associated with deviations in energy metabolism or mitochondrial dysfunctions.

Artificial cartilage bio-matrix formed of hyaluronic acid and Mg2+-polyphosphate

“…Recently, our group provided experimental evidence that polyphosphate (polyP), abundantly present both intracellularly and extracellularly as well as in blood platelets (Morrissey et al, 2012), could serve as an energy source for the generation of chemically utilisable Gibbs free energy after cleavage by ALP (reviewed in: Müller et al, 2015a;Wang et al, 2016). Blood platelets exist in large numbers in synovial fluids from patients with rheumatoid arthritis but are scarce in fluids from osteoarthritis patients, where the density varies between 0 and 10,000/mm 3 (Farr et al, 1984).…”

Morphogenetically-Active Barrier Membrane for Guided Bone Regeneration, Based on Amorphous Polyphosphate

“…In an anticipatory approach, both the polyP-based dental implant (Ca-polyP microparticles) and the barrier membrane are applied on a human skull. Recently we introduced polyP, in the form of Ca-polyP microparticles, as a potent implant material that promotes bone mineralization/regeneration both in vitro and in vivo in animal models [33] (reviewed in [18,19]). Very recently we succeeded in fabricating polyP together with collagen as amorphous hybrid microparticles, in the presence of super-stoichiometric Ca 2+ concentrations, which can be used as grafting material.…”

“…Collagen acts as a structural support for the polyP nanoparticles that are formed in the presence of Ca 2+ . In this hybrid organization polyP retains the characteristic physiological functions (reviewed in [18,19]) to act as a metabolic fuel. Since polyP is prone to enzymatic degradation by the alkaline phosphatase, it is compelling to assume that the released chemical energy is re-utilized as biochemically-useful metabolic energy, required for tissue regeneration [18].…”

A Novel Biomimetic Approach to Repair Enamel Cracks/Carious Damages and to Reseal Dentinal Tubules by Amorphous Polyphosphate

“…Recent data indicate that Pi, released from the natural polymer polyphosphate (polyP) through enzymatic, exohydrolytical cleavage via alkaline phosphatase (ALP) acts as a supply of Pi during bone formation [13,14]. This polymer is present in considerable amounts in the circulating blood serum, as well as within cells, especially within blood platelets (reviewed in: [15]).…”

“…ALP and bone morphogenetic protein-2 (BMP-2), as recently reviewed. [12][13][14] Furthermore, in a recent study we recognized that a-polyP microparticles form a tight interaction especially with the dentin of human teeth [17]. This result in concert with the in vivo result showing that polyP, entrapped in PLGA [poly(D,L-lactide-co-glycolide)]-based microspheres, accelerate bone regeneration in calvarial critical-sized defects faster compared to ß-tri-calcium phosphate (ß-TCP) containing spheres [18] suggested an efficient resealing of the dentinal tubules openings as well as a repair of cracks in the enamel.…”