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

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Bioinformatics and Biomedical Engineering (IWBBIO 2023)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 13919))

Abstract

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).

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Acknowledgements

W.E.G. Müller is the holder of an ERC Advanced Investigator Grant (Grant No.: 268476). In addition, W.E.G. M. has obtained three ERC-PoC Grants (Si-Bone-PoC, Grant No.: 324564; MorphoVES-PoC, Grant No.: 662486; and ArthroDUR, Grant No.: 767234). This work was also supported by the International Human Frontier Science Program and the BiomaTiCS research initiative of the University Medical Center, Mainz. Further support came from a Grant from BMBF (SKIN-ENERGY, Grant No.: 13GW0403A/B).

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Authors and Affiliations

  1. ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany

    Werner E. G. Müller, Shunfeng Wang, Meik Neufurth, Heinz C. Schröder & Xiaohong Wang

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  1. Werner E. G. Müller
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  2. Shunfeng Wang
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  3. Meik Neufurth
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  4. Heinz C. Schröder
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  5. Xiaohong Wang
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Correspondence to Werner E. G. Müller or Xiaohong Wang .

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Editors and Affiliations

  1. University of Granada, Granada, Spain

    Ignacio Rojas

  2. University of Granada, Granada, Spain

    Olga Valenzuela

  3. University of Granada, Granada, Spain

    Fernando Rojas Ruiz

  4. University of Granada, Granada, Spain

    Luis Javier Herrera

  5. University of Granada, Granada, Spain

    Francisco Ortuño

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Müller, W.E.G., Wang, S., Neufurth, M., Schröder, H.C., Wang, X. (2023). Physiological Polyphosphate: A New Molecular Paradigm in Biomedical and Biocomputational Applications for Human Therapy. In: Rojas, I., Valenzuela, O., Rojas Ruiz, F., Herrera, L.J., Ortuño, F. (eds) Bioinformatics and Biomedical Engineering. IWBBIO 2023. Lecture Notes in Computer Science(), vol 13919. Springer, Cham. https://doi.org/10.1007/978-3-031-34953-9_42

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  • DOI: https://doi.org/10.1007/978-3-031-34953-9_42

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