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Protein-bound calcium phosphate in uremic rat serum: a quantitative study

Authors
  • Fan, Hong-Xing1, 2
  • Gou, Bao-Di3
  • Gao, Yu-Xi2
  • Wu, Gang1
  • Liu, Shu-Hu2
  • Li, Fan2
  • Zhang, Tian-Lan3
  • 1 Inner Mongolia University of Science & Technology, Baotou, 014010, People’s Republic of China , Baotou (China)
  • 2 Chinese Academy of Sciences, 19B Yuquan Road, Beijing, 100049, People’s Republic of China , Beijing (China)
  • 3 Peking University School of Pharmaceutical Sciences, 38 Xueyuan Road, Beijing, 100191, People’s Republic of China , Beijing (China)
Type
Published Article
Journal
JBIC Journal of Biological Inorganic Chemistry
Publisher
Springer-Verlag
Publication Date
Aug 24, 2020
Volume
25
Issue
8
Pages
1051–1063
Identifiers
DOI: 10.1007/s00775-020-01807-x
Source
Springer Nature
Keywords
License
Yellow

Abstract

AbstractProtein-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.Graphic abstract

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