20 Biochemistry of Milk Processing 475and the very extensive literature has been reviewed
by Miesel (1998), Pihlanto-Lappälä (2002), Gobbetti
et al. (2002), and FitzGerald and Meisel (2003).
Several bioactive peptides are liberated during the
digestion of bovine milk, as shown by studies of the
intestinal contents of consumers, confirming that
such peptides are liberated in vivo.
Laboratory-scale processes for the production and
purification (e.g., using chromatography, salt frac-
tionation, or UF) of many interesting peptides from
the caseins have been developed; enzymes used
for hydrolysis include chymotrypsin and pepsin
(Pihlanto-Lappälä 2002).
Bioactive peptides may also be produced by en-
zymatic hydrolysis of whey proteins; - and -
lactorphins, derived from -lactalbumin and -
lactoglobulin, respectively, are opioid agonists and
possess angiotensin (ACE) inhibitory activity. The
whey proteins are also the source of lactokinins,
which are probably ACE inhibitory.
Currently, few milk-derived biologically active
peptides are produced commercially. Perhaps the
peptides most likely to be commercially viable in
the short term are the caseinophosphopeptides, which
contain clusters of phosphoserine residues and are
claimed to promote the absorption of metals (Ca, Fe,
Zn), through chelation and by acting as passive
transport carriers for the metals across the distal
small intestine, although evidence for this is equivo-
cal. Caseinophosphopeptides are currently used in
some dietary and pharmaceutical supplements, for
example, in the prevention of dental caries.
The caseinomacropeptide (CMP; ]-CN f106–
169) is a product of the hydrolysis of the Phe 105 -
Met 106 bond of -casein by rennet; during cheese
making, it diffuses into the whey, while the N-
terminal portion of -casein remains with the cheese
curd. CMP has several interesting biological proper-
ties; for example, it has no aromatic amino acids
and is thus suitable for individuals suffering from
phenylketonuria; however, it lacks several essential
amino acids. It also inhibits viral and bacterial adhe-
sion, acts as a bifidogenic factor, suppresses gastric
secretions, modulates immune system responses,
and inhibits the binding of bacterial toxins (e.g., tox-
ins produced by cholera and E. coli). Of particular
interest, from the viewpoint of the commercial
exploitation of CMP, are the relatively high levels of
this peptide present in whey (4% of total casein,
15–20% of protein in cheese whey, an estimated 180
103 mt/yr available globally in whey), and the fact
that it can be quite easily recovered therefrom.
Overall, detailed information is lacking regarding
the physiological efficacy and mechanism of action
of many milk protein–derived peptides and their
possible adverse effects. Technological barriers also
remain in terms of methods for industrial-scale pro-
duction and purification of desired products.INFANT FORMULAS
Today, a high proportion of infants in the developed
world receive some or all of their nutritional require-
ments during the first year of life from prepared
infant formulas, as opposed to breast milk. The raw
material for such formulas is usually bovine milk or
ingredients derived therefrom, but there are signifi-
cant differences between the composition of bovine
and human milk. This fact has led to the develop-
ment of specialized processing strategies for trans-
forming its composition to a product more nutrition-
ally acceptable to the human neonate. Today, most
formulas are in fact prepared from isolated con-
stituents of bovine milk (e.g., casein, whey proteins,
lactose), blended with nonmilk components. This,
combined with the requirement for high hygienic
standards and the absence of potentially harmful
agents, makes the manufacture of infant formula a
highly specialized branch of the dairy processing
industry, with almost pharmaceutical-grade quality
control.
Most infant formulas are formulated by blending
dairy proteins, vegetable (e.g., soy) proteins, lac-
tose, and other sugars with vegetable oils and fats,
minerals, vitamins, emulsifiers, and micronutrients.
The mixture of ingredients is then homogenized and
heat-treated to ensure microbiological safety. Sub-
sequent processing steps differ in the case of dry or
liquid formulas.
The dairy ingredients used are generally deminer-
alized, as the mineral balance in bovine milk is very
different from that in human milk (Burling 2002),
and desired minerals are added back to the formula
as required. Certain proteins (e.g., lactoferrin and -
lactalbumin) are present at higher levels in human
than in bovine milk, and -lg is absent from human
milk. There is interest in fortifying infant formu-
las with -lactalbumin and/or lactoferrin, although
technological challenges exist in the economical pro-
duction of such proteins at acceptable purity.