The Effect of Magnesium on the Activity of Hypophosphatasia-Causing TNSALP Variants

Introduction Hypophosphatasia (HPP) is a metabolic disorder with detrimental effects on the skeleton that is caused by decreased activity of the tissue non-specific alkaline phosphatase (TNSALP) encoded by the ALPL gene. A major function of TNSALP is the hydrolyzation of the mineralization inhibitor pyrophosphate into phosphate ions. The manifestation of HPP is variable and ranges from rare, often lethal forms to mild cases with more frequent estimated incidence rates in adults, leading to a higher fracture risk and reduced quality of life. While enzyme replacement therapy is available for infantile HPP, no adequate treatment has been established for moderate and mild cases.The enzymatic activity of TNSALP requires the presence of bivalent ions such as Mg2+ and Zn2+ as cofactors.