Aspartic acid nucleates the apatite crystallites of bone: a hypothesis.

This review concentrates on the physical state of bone mineral at the nanosize range, where it exists as ultrathin, tiny, platelike particles. They have a distinct X-ray pattern, different from that of apatite crystals, but shared by all bone matter irrespective of source or architecture. The main feature of this diffractogram is a broadened undifferentiated and asymmetric peak at about 32 degrees. The mineral contains several percents of carbonate and also other foreign elements and ions at low concentrations. When new bone is regenerated at a site of damage or resorption, such nanoparticles have to be created as the first step to progressive organizations at higher levels of bone composition. They are generated under cellular control. As they are produced in huge numbers, homogeneous in character, there is no escape from the conclusion that they are nucleated on compounds excreted by the cells and being not foreign to the surrounding. Evidence has been obtained that aspartic acid (AspA), one of the amino acids, which compose all life, has a specific beneficial effect on bone regeneration in an animal model experiment. An analysis of the possible interaction between aspartic acid molecule and the crystallographic unit cell of hydroxyapatite was attempted and is presented in this review. Hydroxyapatite has a large and complex unit cell, and therefore the interaction between such unit and a tiny acid calls for a special array in which the aspartic acid is enclosed inside a carbonated, calcium deficient unit, apparently without changing its external appearance and is able to start assemblage of regular apatite units. The nucleation event depends upon substitution of four carbonate ions in the sites of four phosphate ions. This substitution causes generation of four voids that can accommodate the four terminal oxygen of the aspartic acid. Such unit serves as a nucleating unit.