An equilibrium thermodynamic model of the sequestration of calcium phosphate by casein phosphopeptides

  title={An equilibrium thermodynamic model of the sequestration of calcium phosphate by casein phosphopeptides},
  author={E. Muiehead Little and Carl Holt},
  journal={European Biophysics Journal},
Sequestration of calcium phosphate by caseins occurs in the Golgi region of mammary secretory cells during lactation, where it helps to prevent calcification of the gland and to deliver high concentrations of calcium and phosphate to the neonate in the form of milk. Calcium phosphate nanoclusters are formed when a core of amorphous calcium phosphate is sequestered within a shell of casein or casein phosphopeptides. The nanoclusters can form spontaneously from a supersaturated solution or by… 

An equilibrium thermodynamic model of the sequestration of calcium phosphate by casein micelles and its application to the calculation of the partition of salts in milk

  • C. Holt
  • Chemistry, Medicine
    European Biophysics Journal
  • 2003
According to the calculations, compositions that might lead to pathological calcification in the lumen of the mammary gland were seldom found in primiparous healthy cows in early or mid lactation but occurred more often in multiparous animals, in late lactation and during mastitic infection.

A biological perspective on the structure and function of caseins and casein micelles

Caseins belong to a larger group of secreted calcium phosphate-binding phosphoproteins that have a natively unfolded conformation. Nearly all members of the group are involved in aspects of calcium

A quantitative model of the bovine casein micelle: ion equilibria and calcium phosphate sequestration by individual caseins in bovine milk

An improved model of the partition of caseins and salts in milk is described in which all the phosphorylated residues in competent caseins act together to bind to and sequester the nanoclusters.

Role of calcium phosphate nanoclusters in the control of calcification

It is suggested that the ability of some secreted phosphoproteins to form nanoclusters is physiologically important for the control or inhibition of calcification in soft and mineralized tissues, the extracellular matrix and a wide range of biofluids, including milk and blood.

Structural Biology of Calcium Phosphate Nanoclusters Sequestered by Phosphoproteins

Application of physico-chemical principles and properties of complexes formed by casein, osteopontin, and recombinant phosphopeptides to blood serum, milk, urine, and resting saliva is described to show that under physiological conditions they are in the stable region of their stability diagram and so cannot cause soft tissue calcification.

Invited review: Caseins and the casein micelle: their biological functions, structures, and behavior in foods.

Competent noncasein phosphoproteins have similar patterns of phosphorylation and the same type of flexible, unfolded conformation as caseins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues.


Interactions of casein micelles with calcium phosphate particles.

The HA particles behaved as ion chelators, with the ability to bind the ions contained in the milk serum phase, which disrupted the milk mineral equilibrium, resulting in dissociation of the casein micelles in milk.

Mineralisation of soft and hard tissues and the stability of biofluids.

Calcium phosphates in Ca(2+)-fortified milk: phase identification and quantification by Raman spectroscopy.

Using Raman spectroscopy with a combination of internal and external standards, it was possible to show that the calcium phosphate material formed after Ca(2+) addition to milk was the same as amorphous calcium phosphate nanoclusters present in the absence of added calcium.



Ability of a beta-casein phosphopeptide to modulate the precipitation of calcium phosphate by forming amorphous dicalcium phosphate nanoclusters.

The ability of casein to form nanoclusters in milk suggests a more general mechanism for avoiding pathological calcification and regulating calcium flow in tissues and biological fluids exposed to or containing high concentrations of calcium.

A thermodynamic analysis of the amorphous to crystalline calcium phosphate transformation

A nearly constant ion product was obtained for a tricalcium phosphate (TCP)-like phase suggesting that the molecular unit which governs the solubility of ACP may be similar in composition to TCP.

Study of calcium binding to phosphoserine residues of β-casein and its phosphopeptide (1–25) by 31P NMR

Summary The effect of Ca2+. binding and ionic strength on the physicochemical characteristics of phosphoserine residues was studied on O-phospho-DL-serine, bovine β-casein and its phosphopeptide

A core-shell model of calcium phosphate nanoclusters stabilized by beta-casein phosphopeptides, derived from sedimentation equilibrium and small-angle X-ray and neutron-scattering measurements.

This model suggests that the phosphopeptide is able to arrest the process of growth of the precipitating phase of calcium phosphate at its earliest stages, and a similar role for whole casein could be vital to the normal functioning of the mammary gland during milk secretion.

Amorphous calcium phosphates prepared at pH 6.5 and 6.0

Calculation of the ion equilibria in milk diffusate and comparison with experiment.