title: A review of the biology of calcium phosphate sequestration with special reference to milk.
abstract: In milk, a stable fluid is formed in which sequestered nanoclusters of calcium phosphate are substructures in casein micelles. As a result, calcium and phosphate concentrations in milk can be far in excess of their solubility. Variations of calcium, phosphate and casein concentrations in milks, both within and among species, are mainly due to the formation of the nanocluster complexes. Caseins evolved from tooth and bone proteins well before the evolution of lactation. It has therefore been suggested that the role of caseins in milk is an adaptation of an antecedent function in the control of some aspect of biomineralisation. There is new evidence that nanocluster-type complexes are also present in blood serum and, by implication, in many other closely related biofluids. Because such fluids are stable but nevertheless supersaturated with respect to the bone and tooth mineral hydroxyapatite, they allow soft and mineralised tissues to co-exist in the same organism with relative ease. An appreciable concentration of nanocluster complexes exists in fresh saliva. Such saliva may stabilise tooth mineral and help to repair demineralised lesions. In the extracellular matrix of bone, nanocluster complexes may be involved in directing the amorphous calcium phosphate to intrafibrillar spaces in collagen where they can mature into oriented apatite crystals. Thus, evidence is accumulating that calcium phosphate sequestration by phosphopeptides to form equilibrium complexes, first observed in milk, is more generally important in the control of physiological calcification.
authors: EPSAM, Keele University, Keele, Staffordshire ST5 5BG UK ; Institut Laue Langevin, 71 avenue des Martyrs, CS 20156, 38042 Grenoble cedex 9, France.
authors: Samuel
authors: S
authors: Lenton
authors: Department of Physical Chemistry, Lund University, P.O. Box 124, S-221 00 Lund, Sweden.
authors: Tommy
authors: T
authors: Nylander
authors: EPSAM, Keele University, Keele, Staffordshire ST5 5BG UK ; Institut Laue Langevin, 71 avenue des Martyrs, CS 20156, 38042 Grenoble cedex 9, France.
authors: Susana C M
authors: SC
authors: Teixeira
authors: Institute of Molecular, Cell and Systems Biology, University of Glasgow, RB413A Level B4 Joseph Black Building, Glasgow, G12 8QQ UK.
authors: Carl
authors: C
authors: Holt
keywords: Amorphous calcium phosphate; Blood; Bone; Milk; Saliva; Tooth; Urine
references: J Mol Med (Berl). 2008 Apr;86(4):379-89
references: 18080808
references: Dalton Trans. 2009 Apr 21;(15):2665-72
references: 19333487
references: Faraday Discuss. 2012;159:357-370
references: 25383016
references: Acta Biomater. 2010 Sep;6(9):3362-78
references: 20167295
references: Calcif Tissue Res. 1978 Aug 18;25(3):209-16
references: 30523
references: J Dairy Res. 1982 Feb;49(1):29-38
references: 6804550
references: Eur Biophys J. 2004 Aug;33(5):435-47
references: 14735250
references: Arch Oral Biol. 1973 Nov;18(11):1385-92
references: 4518758
references: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4060-5
references: 12646701
references: Circ Res. 2011 Jun 10;108(12):1494-509
references: 21659653
references: J Dairy Sci. 2014;97(1):136-46
references: 24268404
references: J Clin Invest. 1962 Jul;41:1454-71
references: 14004728
references: J Biol Chem. 2003 Jun 13;278(24):22153-60
references: 12676928
references: Science. 2008 Dec 19;322(5909):1819-22
references: 19095936
references: Calcif Tissue Res. 1972;10(3):171-97
references: 4674170
references: Calcif Tissue Int. 2003 May;72(5):583-91
references: 12616327
references: Nat Mater. 2010 Dec;9(12):1004-9
references: 20972429
references: J Dent Res. 2010 Apr;89(4):355-9
references: 20200415
references: J Clin Invest. 1961 Apr;40:723-30
references: 13782899
references: FEBS J. 2009 Apr;276(8):2308-23
references: 19292864
references: Eur Biophys J. 2004 Aug;33(5):421-34
references: 14735251
references: Biochem Biophys Res Commun. 2001 Jan 19;280(2):460-5
references: 11162539
references: Acta Biomater. 2014 Jan;10(1):494-507
references: 24140612
references: Calcif Tissue Int. 1985 Jul;37(4):401-10
references: 3930038
references: J Agric Food Chem. 2010 Apr 14;58(7):4440-7
references: 20225854
references: Anal Biochem. 1981 May 1;113(1):154-63
references: 7270880
references: Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11356-61
references: 15272073
references: Acta Biomater. 2014 May;10(5):2241-9
references: 24434535
references: FASEB J. 2004 Apr;18(6):734-6
references: 14766790
references: J Struct Biol. 2014 Mar;185(3):383-96
references: 24316224
references: Biomatter. 2011 Oct-Dec;1(2):121-64
references: 23507744
references: Calcif Tissue Int. 2010 Jan;86(1):42-6
references: 19998030
references: Chem Rev. 2008 Nov;108(11):4670-93
references: 18831570
references: Protein Expr Purif. 2009 Sep;67(1):23-34
references: 19364535
references: Biophys J. 2010 Dec 15;99(12):3986-95
references: 21156141
references: QJM. 2002 Jan;95(1):3-13
references: 11834767
references: J Dairy Sci. 1992 Apr;75(4):971-5
references: 1578034