Casein proteolysis in human milk: tracing the pattern of casein breakdown and the formation of potential bioactive peptides

Abstract

The protein and peptide fraction of human milk samples collected from mothers of pre- and full-term infants in the first week after parturition was analysed by use of liquid chromatography-mass spectrometry and tandem mass spectrometry. By characterising the peptide sequence, we defined the pathway of casein hydrolysis which leads to the formation of small peptides through intermediate oligopeptides. It was found that the action of a plasmin-like enzyme acting on specific lysine residues is the primary step in casein degradation. This is followed by endopeptidases and/or exopeptidases mediated cleavage of the oligopeptides which, in turn, produces a multiplicity of short peptides differing by one or more amino acid residues. In this process, a series of potentially bioactive peptides (opioid, phosphopeptides) and their precursors are produced.

Bioactive peptides released from in vitro digestion of human milk with or without pasteurization

“…Except residues 51-59, the presence of these peptides in undigested HM has been observed previously (14,15). Two peptides of residues 1-18 and 1-23 are considered human counterparts of caseinophosphopeptides because they have the "acid motif " SerP-SerP-SerP-Glu-Glu, essential for the mineral-carrier potential (11).…”

“…Articles RESULTS Peptides in undigested HM were analyzed prior to the analysis of digesta as background data (Figure 1), because some of the protein-derived peptides are potentially present in undigested HM (14,15). As can be seen, a large number of peptides were observed.…”

“…In agreement with previous observations, most of the peptides present in undigested HM were derived from CNs, and no peptide was identified from major whey proteins such as α-LA and LF. The most abundant peptides are derived from β-CN, reflecting its high susceptibility to plasmin-mediated proteolysis as well as the high content of this casein subunit in HM (14,16). Focusing on bioactive peptides in undigested HM, as shown in Table 1 (14,15,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), two caseinophosphopeptide homologues, a possible opioid peptide or propeptide, and an antibacterial peptide were identified.…”

Bioactive Casein Phosphopeptides in Dairy Products as Nutraceuticals for Functional Foods

“…The cited literature has highlighted that bioactive peptides may be released in vitro or in vivo by digestive and bacterial enzymes starting from casein or generally inactive precursors [151,[154][155]. We have examined the case of casein-derived phosphopeptides that can be applied as dietary supplements in "functional foods" and produced on an industrial scale.…”

Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects

“…Milk is a rich source of bioactive substances with benefi cial effects for humans [Expósito and Recio 2006, Korhonen and Pihlanto 2006, Mils et al 2011, Phelan et al 2009]. Milk protein derivatives are physiologically active peptides which are released in the digestive tract [Chabance et al 1998, Ferranti et al 2004, Meisel and Frister 1989, Parrot et al 2003, Svedberg et al 1985. β-casomorphins and casein phosphopeptides (CPP) are produced in vivo after the consumption of dairy products, including milk, fermented milk, cheese and yogurt [Chabance et al 1998, Hernández-Ledesma et al 2004, Kasai et al 1992, Meisel and Frister 1989, Parrot et al 2003, Svedberg et al 1985.…”