Milk Peptides

Definition
Milk peptides are formed from milk proteins through enzymatic breakdown by digestive enzymes or by the proteinases of lactobacilli during the fermentation of milk. These peptides directly influence numerous biological processes evoking behavioral, gastrointestinal, hormonal, immunological, neurological, and nutritional responses.

Discovery
The major protein fractions in bovine milk include a-LA, ß-LG, caseins, immunoglobulins, lactoferrin, proteose- peptide fractions (heat-stable, acid soluble phosphoglycoproteins and minor whey proteins such as transferrin and serum albumin. Antimicrobial milk proteins, such as lactoferrin, were described in early literature1. Casecidin, obtained by chymosin digestion of casein at neutral pH, was among the first defense peptides actually purified and exhibited activity in vitro against Staphylococcus, Sarcina, Bacillus subtilis, Diplococcus pneumoniae, and Streptococcus pyogenes2. Milk also contains peptides that exhibit antifungal properties like lactoferrin or its peptides (ex. lactoferricin B., in combination with azole antifungal agents, has been demonstrated with Candida albicans3.

Stuctural Characteristics
Milk peptides have a high content of negative charges they will efficiently bind divalent cations with the formation of soluble complexes. Complexes of peptides and minerals of Fe, Mg, Mn, Cu and Se are reported. The high content of negative charges makes these phosphopeptides resistant to further hydrolysis. Milk caseins are easily degradable proteins due to their random coil structure. The whey proteins, b-lactoglobulin, a-lactalbumin and lactoferrin also give rise to peptides with mineral binding abilities. These proteins are regarded as more resistant to enzymatic attack and undergo hydrolysis much more slowly than the caseins4.

Mode of action
Milk peptides may affect mucosal immunity possibly by guiding local immunity until it develops its full functionality5. Several milk peptides have been shown to have antihypertensive effects in animal and in clinical studies. The most studied mechanism underlying the antihypertensive effects of milk peptides is inhibition of angiotensin-converting enzyme6. Angiotensin-converting enzyme inhibition (ACE. is an enzyme that plays a crucial role in the function of the renin-angiotensin system (RAS). The RAS is an important regulator of blood pressure and fluid and electrolyte balance. In the RAS, angiotensin I is converted to angiotensin II by ACE. Angiotensin II is a strong vasoconstrictor that induces release of aldosterone and therefore increases sodium concentration and furthers the blood pressure. ACE inhibitors have 2 effects on the renin-angiotensin system. They reduce production of angiotensin II and inhibit the degradation of the vasodilator.

Several milk peptides have opioid-like activities are derived from ??casein, called ?-exorphins, and those derived from ?-casein are called casoxins. These peptides have been shown to lower blood pressure. Because the antihypertensive effect of ?-lactorphin was completely prevented by an opioid receptor antagonist naloxone, it has been proposed that the antihypertensive effect is mediated via opioid receptors.

Functions
Antimicrobial Peptides - Milk contains a variety of components that provide immunological protection and facilitate the development of neonatal immune competence6. Lactoferrin is another milk bioactive compound with nutritional and health promoting properties; it modulates the microbial intestinal environment, displays anti-microbial activity against various pathogens and stimulates the establishment of beneficial microflora.

Antihypertensive Peptides (ACE Inhibitors) - Antihypertensive peptides inhibit the angiotensin converting enzyme (ACE), ACE converts angiotensin I to angiotensin II, increasing blood pressure and aldersterone, and inactivating the depressor action of bradykinin7.

Antithrombotic Peptides- Antithrombotic peptides are present in milk, involved in milk clotting, defined by the interaction of ?-CN with chymosin and blood clotting processes8.

Caseinophosphopeptides- Casein phosphopeptides (CPP) have been identified after trypsin release from as1-, as2-, and ß-CN. This complex formation results in an increased solubility which, in turn, provides enhanced absorption of calcium across the distal small intestines of animals fed casein diets in comparison to control animals fed soy-based diets7.

Immunomodulatory Peptides - Immunomodulatory milk peptides affect both the immune system and cell proliferation responses. ß-casokinins inhibit ACE enzymes that are responsible for inactivating bradykinin, a hormone with immune enhancing effects7.

References
1. Bullen JJ, Rogers HJ, Leigh L (1972). Iron binding proteins in milk and resistance to E. coli infections in infants. Br. Med, 1: 69–75.
2. Lahov E and W Regelson (1996) Antibacterial and immunostimulating casein-derived substances from milk: casecidin, isracidin peptides. Food Chem. Toxicol, 34: 131–145.
3. Wakabayashi H, Abe S, Okutomi T, Tansho S, Kawase K, Yamaguchi H (1996). Cooperative anti-Candida effects of lactoferrin or its peptides in combination with azole antifungal agents. Microbiol. Immunol, 40: 821–825.
4. Vegarud GE, Langsrud T, Svenning C (2000.. Mineral-binding milk proteins and peptides; occurrence, biochemical and technological characteristics. British Journal of Nutrition, 84(1): 91-98.
5. Politis I and Chronopoulou R (2007). Milk Peptides and Immune Response in the Neonate. Advances in Experimental Medicine and Biology, 606: 253-269.