Inorganic Polyphosphate and Alkaline Phosphatase/Adenylate Kinase: Key Components of the Physiological ATP-Dependent Wound Repair and Mode of Action.

Abstract

Platelets play a crucial role in physiological wound healing, providing the energy required for this highly ATP-dependent repair/regeneration process. The formation of these cell fragments, which accumulate the energy-rich polymer inorganic polyphosphate (polyP) in their dense granules, is described. The possible mechanism of storage of the polyanionic polyP in these organelles together with counterions, particularly calcium and serotonin, which is present as a cation in the acidic interior of the granules, is discussed. Synthetic polyP can be used for wound therapy, either as a soluble sodium salt or as calcium-polyP nanoparticles, which are converted into the metabolically active coacervate at the site of injury. A model based on the Donnan equilibrium is presented that explains the uneven distribution of positive and negative charges within the nanoparticulate and coacervate forms of polyP. Another focus of this chapter is on the central role of the enzyme alkaline phosphatase (ALP), present in wound fluid, in polyP metabolism and the conversion of the chemical energy stored in polyP into the metabolically usable energy of the energy carrier ATP. The mechanism of ALP-catalyzed hydrolytic cleavage of the energy-rich phosphoanhydride bonds of polyP is discussed, as are the subsequent reactions that keep this enzyme running.