Figure 1.
Bone formation is reduced in PKU at least in part due to energy deficit. Bone formation requires production of massive ATP from oxidative phosphorylation, energy required for production of the Type I collagen matrix and for mineralizing the matrix, dependent in large part on phosphate transport collagen synthesis,33 diagrammed as green collagen matrix and as phosphate transport (top panel). In PKU, complex 1 activity is significantly compromised with reduced ATP and bone matrix formation (bottom panel).27 Similar energy dependent effects occur in aging and in other metabolic diseases, the detailed mechanisms of which are not yet defined.34–36