No abstract

The present paper is devoted to the study of short peptides derived from milk proteins with physiological activities. Some of them behaved as opioids, enzyme inhibitors that convert angiotensin I, peptides that enhance calcium absorption, antiaggregating and antithrombotic peptides, and immunomodulating peptides. Some possessed several physiological properties, such as the C-terminal part of bovine alpha s1-casein. A strategic zone, containing immunostimulating and opioid peptides, could be located in cow and human beta-caseins. Few of these peptides or precursor peptides have so far been characterized in vivo in blood or brain after ingestion of milk. If, in the future, some of the active peptides cannot be characterized in vivo, they can all nevertheless be synthesized and used either as food additives or in pharmacology.

The first part of the present review is focused on structural aspects concerning the so far studied casein fractions of various origins: they are compared to the four classical major bovine caseins (alpha s1-, alpha s2-, beta- and kappa). The calcium-sensitive casein fractions are always phosphorylated whereas kappa-caseins are glycosylated. The study of the casein genes showed that the calcium-sensitive caseins diverged from a common ancestral gene and during the evolution, intergenic and intragenic duplications occurred. The considerable conservation of the phosphorylation sites emphasizes the importance of phosphorylated residues for the function of caseins, i.e. the formation of micelles and the binding of Ca2+. In kappa-caseins all the prosthetic sugar groups are linked by O-glycosidic linkages: their number varies from 0 to 5 in bovine kappa-casein and up to 10 in human kappa-casein. The structures of the known kappa-casein carbohydrate moieties are described. Finally the milk clotting process (interaction kappa-casein/chymosin) is compared to the blood clotting process (interaction fibrinogen/thrombin): a large number of similarities could be noted between both clotting phenomena. The second part of the review is devoted to the study of short casein peptides endowed with various biological activities. Some of them behaved as immunomodulators or casomorphins or angiotensin I converting enzyme inhibitors; others demonstrated an effect on platelet functions. A 'strategic zone' containing immunostimulating and opioid peptides could be located in cow and human beta-caseins. Furthermore bitter peptides, emulsifying peptides, calcium absorption enhancing peptides, chymosin-inhibiting peptides, have also been described and several further properties have been attributed to the kappa-caseinoglycopeptide; two tetrasaccharides isolated from the latter possess blood group activities. In conclusion caseins, the main milk proteins, should not only be considered as a nutriment but as a possible source of biologically active components. If, in the future, some of the discussed active peptides cannot be characterized in vivo, they can all, nevertheless, be synthesized and used either as food additives or in pharmacology.