Protein and Nonprotein Nitrogen Components in Human Milk, Bovine Milk, and Infant Formula: Quantitative and Qualitative Aspects in Infant Nutrition (1997)

During the last decade, the discussion regarding the quantity of protein in feeding term and preterm infants had led to numerous controversial publications. The protein quality of bovine milk has been extensively studied as a dairy product, but the processing of infant formula has revealed new questions about the type of heat treatment to be used to produce microbiologically safe and highly nutritious formulae and to the impact of protein hydrolysis on nutrient bioavailability, e.g., during the production of hypoantigenic formula. Feeding preterm infants with donor milk also requires processing of human milk, which affects the functional properties of certain milk components. From the qualitative point of view, some major milk proteins seem to be well characterized. Functional aspects of side chains like carbohydrates in lactoferrin, secretory IgA (sIgA), casein, and others, however, need further investigation. In addition, during the gastrointestinal transit of proteins in milk or infant formula, a variety of smaller peptides and amino acids are formed, which may exert local or systemic functions, e.g., as bioactive or immunomodulatory components. Here, we will focus on proteins in human and bovine milk; the protein quantity necessary for appropriate growth; the content and utilization of nonprotein nitrogen; the nutritional bioavailability of milk proteins from human milk; and the effect of processing of infant formula, including hypoantigenic products, on the formation of bioactive peptides and on possible functions of the glycan part of some proteins. COMPARISON BETWEEN HUMAN MILK, BOVINE MILK, AND INFANT FORMULA The total milk protein consists of two major groups of constituents, caseins and whey proteins; some minor components such as enzymes or growth factors; and proteins within the milk fat globule membrane (1-4). In mature human milk, the ratio of whey protein to casein is about 60:40 to 50:50, whereas in bovine milk, casein constitutes ≈80% of the total protein (1,5,6). The difference in the gross protein composition of human and bovine milk after SDS-gel electrophoresis is shown in Fig. 1. Whereas lactoferrin, sIgA, serum albumin, and α-lactalbumin are the main components in human whey, β-lactoglobulin is the dominant soluble protein in bovine milk (compare lanes 2 and 3 with lane 6). The latter has been detected in human milk as well, but only in minute quantities (7,8), possibly originating from the cow's milk protein intake of the mother. The caseins in human milk are β- and κ-casein; α-casein, which is regularly found in bovine milk, seems to be absent in human milk (compare lanes 4 and 5 with lane 7). Table 1 summarizes the composition, the concentration, and the degree of glycosylation of the major proteins in human and bovine milk. An increasing number of publications demonstrate that from a biochemical and physiological point of view, the glycosylation of proteins and lipids plays an important role in the function of these components. It is currently discussed that glycoproteins and glycolipids, for example, exert antiinfective properties to prevent the attachment of pathogenic microorganisms to epithelial cells, that oligosaccharides and other carbohydrates affect the interaction of cell adhesion molecules with endothelial cells, and that negatively charged components like acidic oligosaccharides and glycoconjugates enhance mineral and trace element absorption (9-11). The latter effect would be comparable to the possible impact of phosphopeptides from human or bovine milk on the absorption of, e.g., calcium or zinc. Further functional aspects of the carbohydrate moiety of glycoconjugates are discussed in the final section on current topics in human milk protein research. Immunoglobulins, lactoferrin, and casein are glycosylated to a different degree in both human and bovine milk. For example, in κ-casein, all sugar chains are of the O-glycan type (12); no carbohydrate parts linked to asparagine have been detected so far. A characteristic of human κ-casein compared with the bovine subunit is not only the higher amount of carbohydrates (40-60% vs. 10%), and therefore the higher variety of possible sugar linkages, but the presence of ≤10 prosthetic sugar groups in human casein (only one in bovine casein) (12-14). There are pronounced differences in the casein subunit patterns for premature milk, colostrum, and mature milk. In general, κ-casein subunits in human milk are not detectable until day 3-4 postpartum (5). In early premature milk the glycosylated components (κ-casein) are present at very low concentrations or are missing (Fig. 2)(15,16). The glycosylated subunits are also lower in colostrum (>day 3 postpartum) compared with mature milk of mothers with term infants, although a subunit pattern more similar to that of mature milk is established. β-casein seems to exist with a similar pattern in premature milk, but the concentrations of most subunits are higher in colostrum and milk of mothers with term infants (Fig. 2). The marked increase in casein concentration and the concomitant decrease in whey proteins during the first days of lactation leads to a changing proportion of casein as a percentage of total protein. The ratio of whey proteins to casein is high (≈90:10) at the onset of lactation and changes rapidly within days to a ratio of 60:40 or even 50:50 in mature milk (5,16). These observations suggest a different hormonal regulation of β-casein and κ-casein synthesis. Whether both-protein synthesis and side chain modifications (glycosylation and phosphorylation)-of the subunits are controlled by the same regulatory is other milk all casein subunits are a of amino and for the casein as be to enhance calcium absorption and with In addition, like other glycosylated casein subunits may the growth of or with or to prevent adhesion to epithelial proteins are to be in the in synthesis and in of the glycosylated part of and on the will be discussed There are other proteins and in human as well as in bovine milk that may have is the of to all in we the to Table is no that the protein content of most of the term and preterm infant leads to appropriate the discussion on the type of protein to be used and on the protein for both term and preterm infants A controversial is the and lower of protein has been extensively discussed at a on protein in Here, we will only questions to the protein intake from human milk and infant for term The protein content of bovine milk on which most infant formula are is 3 to 4 that of human milk. 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These are in to preterm infants, the of utilization similar to the in the compared the nutritional of a whey formula and a formula on protein in infants from to 3 of found no difference in and although the lower in the There also higher and It seems that as in with an the not used but to to protein These and from other revealed that further for on and trace element in infants on formula, are necessary final about be In to in infants, some suggest that feeding a protein or an amino the of functions It has been shown in that the on the of and are seems that and as well as be by protein. would that proteins a higher of hydrolysis The also be to a difference in which has been or in It has also been shown that proteins a higher of peptides or amino in the is a difference feeding protein Whether these differences are of to however, to be further and There is some that human milk may of the the absorption of and the of the of has not been that has a effect from in infants at are or the that and a the of has to be that human milk also to an to certain by the be on to the infant by In general, seems that during the first of with the of other may the of and of gastrointestinal to cow's milk in infants at to the of There is an increasing number of on the of peptides from of proteins from human milk or infant formula In the we will bioactive from the of proteins that have local on the or systemic after with a possible on mineral and trace element absorption may be during hydrolysis of milk proteins. It has been that caseins and casein phosphopeptides from in or in enhance calcium absorption of to increase calcium in the In a calcium in however, the difference a casein formula and a whey protein formula with to calcium not of of the the absorption from human milk, which higher in of the other Whether casein phosphopeptides from human milk are more in calcium absorption bovine milk casein phosphopeptides from infant is not infant a of heat is possible that not only has the of proteins but also to In the same The that from of protein. It has been shown that protein has a effect on absorption a of the protein of infant formula not be by a calcium or peptides from bovine casein are or from whey proteins are such peptides from and exert are also as to from the peptides or These two and from α-lactalbumin or β-lactoglobulin as in In all κ-casein as as the effect of casein and on gastrointestinal in that the of as well as the gastrointestinal transit of the casein whey protein The differences the groups by the with the The is that peptides from casein during gastrointestinal by interaction with The that different peptides with may be during from the casein of bovine milk. These peptides may with in the and by The main physiological role of seems to be local on the gastrointestinal An of and absorption by and in the and to be a major of In addition, may affect nutrient absorption and by the of and peptides may be from human milk as well as from infant formula during the the for a functional role has been only for the so HUMAN on human milk proteins on minor components like growth or that to affect and absorption of and which major milk proteins like and or minor components like soluble cell adhesion functions of lactoferrin, such as as a growth a an and and in absorption have been discussed It that the glycosylation pattern of in some of functions, e.g., of that is not in the gastrointestinal and the to and may the of in the major sIgA, not or in to other major but the by of and of an interaction and IgA to an of and to an of attachment to epithelial to the interaction the for a function of secretory IgA of the of milk or like other glycoproteins and oligosaccharides in human milk, may with an in and of discussed by the of human is by the epithelial which as a secretory in the casein of human milk and as a in human milk fat The effect of from human milk fat in the of adhesion to epithelial has been by epithelial and The that milk components with the attachment of pathogenic and may therefore be as part of the of the human that of milk and in the of some but not all infants, that may be a to the of in antiinfective Fig. 4 the of to epithelial by or with carbohydrates on the of epithelial and and other to glycolipids, and oligosaccharides in human milk are to be soluble for pathogenic microorganisms that may prevent the of, for example, with epithelial and exert Table 4 the of some pathogenic and for which in human milk as soluble as oligosaccharides or as part of These components of human milk all be to be for adhesion to epithelial the first of an may be by human milk oligosaccharides and human milk has been to the of preterm During the of a of seems to an by nutritional like acids or may a of the the and to Immunoglobulins, growth and are discussed as for the effect of human milk. cell adhesion which have been detected in human milk at of lactation may well to are in the of the interaction of with or with other a shown in Fig. These of to adhesion on endothelial by the of may be are to by soluble of in certain Whether soluble cell adhesion molecules in human milk have a function for the e.g., as requires further cell adhesion is present in human milk as part of the with the endothelial the milk different carbohydrate the milk is to with on is that milk and endothelial have different functions, which need to be further on human milk has led to the of new components that are not detectable or in regarding glycosylation or from in bovine milk and in most of the infant the components have a for the infant human milk. The protein intake necessary for appropriate growth is not to formula a formula with a protein content of for the first 2 of the of a formula with a protein content of seems to be the protein content of most current high for infants There is increasing that from other components of the an important role in the growth and of has been in milk components that may have such as and Whether infant be with such components be are necessary to both the of components and increase about the of these milk components. only are milk proteins a of amino and for the but may in that affect mineral absorption or Further are necessary to changes in the nutritional bioavailability of amino acids and peptides from used to milk. is important in the of protein as hypoantigenic The for the of these as a or have not been It is well that human milk a variety of and components that be found in bovine milk and in most of the infant soluble cell adhesion molecules have have been detected in human milk at of Whether have a function in the e.g., as an requires further investigation. glycosylated in milk, the have been the focus of in human milk. on human milk glycoconjugates by the and SDS-gel electrophoresis of human and bovine milk whey and casein lane human whey lane human whey lane human casein lane human casein lane bovine casein lane bovine whey of human milk casein by from premature milk and early and milk from mother. colostrum day 3 and day of term milk. of amino acids in infants and in and term infants as intake of of as by on the of a The the and the of to The is and with the endothelial by are and on the endothelial to on the and adhesion to the is by and possibly by other that are by the and to the endothelial or by the