Physiological Polyphosphate: A New Molecular Paradigm in Biomedical and Biocomputational Applications for Human Therapy

Inorganic polyphosphates (polyP) consist of linear chains of orthophosphate units linked together by high-energy phosphoanhydride bonds. The family of polyP molecules are evolutionarily old biopolymers and found from bacteria to man. PolyP is exceptional, no other molecule concentrates as much (bio)chemically usable energy as polyP in animals, including humans. Before this discovery, we found that the long-neglected polymer provides orthophosphate units required for bone (hydroxyapatite) synthesis. Hence, polyP is a cornerstone for bone synthesis and repair, especially in higher animals. Besides its importance for regenerative medicine, especially for the reconstitution of osteoarticular impairments/defects, a further imperative property could be attributed the polyP. This polymer is the only extracellular generator of metabolic energy in the form of ATP. While the mitochondria synthesize ATP in large amounts intracellularly, it is polyP, which functions as the storage for extracellular ATP. After enzymatic hydrolysis of polyP by alkaline phosphatase (ALP) the released free energy is partially stored in ADP (formed from AMP), which in the second step is up-phosphorylated to ATP by adenylate kinase (ADK). In turn, the two enzymes ALP and ADK are the biocatalytic proteins that conserve the released free energy and store it in ATP, especially in the extracellular space. In a proof-of-concept, we could demonstrate that polyP is an essential component for human regeneration processes, especially in those regions, which are poorly vascularised, like in bone, cartilage and wounds (including chronic wounds).