Protein-bound
calcium (prCa) constitutes about 40% of serum total
calcium, in which
albumin is the most dominant
protein. Given the chemical interaction between
calcium and
phosphate (Pi), the increased serum Pi in
chronic kidney disease may cause changes in the composition and structure of the prCa fraction. Here, we report the
phosphate binding on the
protein-bound
calcium in uremic rat serum. Using
adenine-fed rats as a uremic model, we separated the
calcium and
phosphate fractions in rat serum by ultrafiltration, and found that the level of
protein-bound
phosphate (prPi) in the uremic serum was markedly higher than in control. The elevated prPi level was comparable to the prCa level, consistent with the presence of
protein-bound
calcium phosphate pr(Ca)j-m(CaPi)m. We then confirmed its presence by ex vivo X-ray absorption near-edge structure spectroscopy, revealing the discrete state of the
calcium phosphate clusters associated with
protein. Finally, in a quantitative investigation using Ca- and Pi-boosted serum, we discovered the threshold concentration for the Pi binding on prCa, and determined the binding constant. The threshold, while preventing Pi from binding to prCa in normal condition, allows the reaction to take place in
hyperphosphatemia conditions. The
protein-bound
calcium phosphate could act as a link between the metabolism of
serum proteins and the homeostasis of
phosphate and
calcium, and it deserves further investigation whether the molar ratio of (prPi/prCa)⋅100% may serve as a serum index of the
vascular calcification status in
chronic kidney disease.