Bioactive Proteins and their Physiological Functions in Milk

Author(s): Fengtao Ma, Jingya Wei, Liyuan Hao, Qiang Shan, Hongyang Li, Duo Gao, Yuhang Jin, Peng Sun*

Journal Name: Current Protein & Peptide Science

Volume 20 , Issue 7 , 2019


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Abstract:

Milk is the basic food for infants and newborn animals, providing a rich source of proteins, carbohydrates, minerals, and vitamins. Milk also provides nourishment for people of all ages due to its abundant nutrients, and it is used in the manufacture of numerous health-related products. Milk contains caseins and whey proteins as the two major protein classes. Caseins fall into four major types known as αs1-, αs2-, β- and κ-casein, whereas whey proteins comprise a mixture of globular proteins including β-lactoglobulin, α-lactalbumin, serum albumin, lactoferrin, and other bioactivators. The various biological activities of these proteins are involved in preventing and treating numerous nutritional, physiological and metabolic diseases. This article reviews the bioactivities and functions of milk proteins, which may shed light on future application of milk bioactive substances.

Keywords: Milk protein, casein, whey protein, bioactivity, physiological function, bioactivators.

[1]
Mulvihill, D.M.; Ennis, M.P. Functional milk proteins: Production and utilization. In: Fox P.F., McSweeney P.L.H. (eds) Advanced Dairy Chemistry—1 Proteins; Springer, Boston, MA.,. , 2003; pp. 1175-1228.
[2]
Le, T.T.; Deeth, H.C.; Larsen, L.B. Proteomics of major bovine milk proteins: Novel insights. Int. Dairy J., 2017, 67, 2-15.
[3]
Fox, P.F.; Uniacke-Lowe, T.; McSweeney, P.L.H.; O’Mahony, J.A. Milk proteins. In Dairy chemistry and biochemistry (2nd ed.). , 2015; pp. 145-205.
[4]
Horne, D.S. A balanced view of casein interactions. Curr. Opin. Colloid In., 2017, 28, 74-86.
[5]
Shahbazi, R.; Davoodi, H.; Mortazavian, A.M.; Esmaeili, S. The biologic effects of casein and casein-derived bioactive peptides. Iran. J. Nutr. Sci. Food Technol., 2013, 7, 811-820.
[6]
Swaisgood, H.E. Chemistry of the caseins. In: Fox, P.F.; Editor.Advanced dairy chemistry. 1: Proteins, 2nd ed; . London: Elsevier Applied Science;. , 1992; pp. 63-110.
[7]
Keppler, J.K.; Martin, D.; Garamus, V.M.; Berton-Carabin, C.; Nipoti, E.; Coenye, T.; Schwarz, K. Functionality of whey proteins covalently modified by allyl isothiocyanate. Part 1 phusicochemical and antibacterial properties of native and modified whey proteins at pH 2 to 7. Food Hydrocoll., 2017, 65, 130-143.
[8]
Lin, S.H.; Leong, S.L.; Dewan, P.K.; Bloomfield, V.A.; Morr, C.V. Effect if calcium ion on the structure of native bovine casein micelles. Biochemistry, 1972, 11, 1818-1821.
[9]
Yano, M.; Nagasawa, S.; Suzuki, T. Purification and properties of bovine serum kallikrein activated with casein. J. Biochem., 1970, 67, 713-725.
[10]
Lee, Y.M.; Skurk, T.; Hennig, M.; Hauner, H. Effect of a milk drink supplemented with whey peptides on blood pressure in patients with mild hypertension. Eur. J. Nutr., 2007, 46, 21.
[11]
Mora-Gutierrez, A.; Farrell, H.M.; Attaie, R.; Mcwhinney, V.J.; Wang, C. Influence of bovine and caprine casein phosphopeptides differing in alphas1-casein content in determining the absorption of calcium from bovine and caprine calcium-fortified milks in rats. J. Dairy Res., 2007, 74, 356-366.
[12]
Bouhallab, S.; Bouglé, D. Biopeptides of milk: Caseinophosphopeptides and mineral bioavailability. Reprod. Nutr. Dev., 2004, 44, 493-498.
[13]
Miquel, E.; Alegría, A.; Barberá, R.; Barbera, R.; Farre, R. Casein phosphopeptides released by simulated gastrointestinal digestion of infant formulas and their potential role in mineral binding. Int. Dairy J., 2006, 16, 992-1000.
[14]
Miquel, E.; Farré, R. Effects and future trends of casein phosphopeptides on zinc bioavailability. Trends Food Sci. Technol., 2007, 18, 139-143.
[15]
Cosentino, S.; Donida, B.M.; Marasco, E.; Marasco, E.; Favero, E.D.; Cantù, L.; Lombardi, G.; Colombini, A.; Iametti, S.; Valaperta, S.; Fiorilli, A.; Tettamanti, G.; Ferraretto, A. Calcium ions enclosed in casein phosphopeptide aggregates are directly involved in the mineral uptake by differentiated HT-29 cells. Int. Dairy J., 2010, 20, 770-776.
[16]
Kitts, D.D.; Nakamura, S. Calcium-enriched casein phosphopeptide stimulates release of IL-6 cytokine in human epithelial intestinal cell line. J. Dairy Res., 2006, 73, 44-48.
[17]
Reyes-Díaz, A.; González-Córdova, A.F.; Hernández-Mendoza, A. Immunomodulation by hydrolysates and peptides derived from milk proteins. Int. J. Dairy Technol., 2018, 71, 1-9.
[18]
Lin, C.Y.; Mcallister, A.J.; Ngkwaihang, K.F.; Hayes, J.F.; Batra, T.R.; Lee, A.J.; Roy, G.L.; Vesely, J.A.; Wauthy, J.M.; Winter, K.A. Association of milk protein types with growth and reproductive performance of dairy heifers. J. Dairy Sci., 1987, 70, 29-39.
[19]
Fernández-Tomé, S.; Martínez-Maqueda, D.; Girón, R.; Girón, R.; Goicoechea, C.; Miralles, B.; Recio, I. Novel peptides derived from αs1-casein with opioid activity and mucin stimulatory effect on HT29-MTX cells. J. Funct. Foods, 2016, 25, 466-476.
[20]
Hebb, A.L.O.; Poulin, J.F.; Roach, S.P.; Zacharko, R.M.; Drolet, G. Cholecystokinin and endogenous opioid peptides: interactive influence on pain, cognition, and emotion. Prog. Neuro-Psychoph., 2005, 29, 1225-1238.
[21]
Witt, K.A.; Davis, T.P. CNS drug delivery: Opioid peptides and the blood-brain barrier. AAPS J., 2006, 8, E76-E88.
[22]
Arima, S.; Niki, R.; Takase, K. Structure of β-casein. J. Dairy Res., 1979, 46, 281-282.
[23]
Righetti, P.G.; Nembri, F.; Bossi, A.; Mortarino, M. Continuous enzymatic hydrolysis of β-casein and isoelectric collection of some of the biologically active peptides in an electric field. Biotechnol. Prog., 2010, 13, 258-264.
[24]
Koudelka, T.; Dehle, F.C.; Musgrave, I.F.; Hoffmann, P.; Carver, J.A. Methionine oxidation enhances k-casein amyloid fibril formation. J. Agric. Food Chem., 2012, 60, 4144-4155.
[25]
Liu, J.; Dehle, F.C.; Liu, Y.; Bahraminejad, E.; Ecroyd, H.; Thorn, D.C.; Carver, J.A. The effect of milk constituents and crowding agents on amyloid fibril formation by κ-casein. J. Agric. Food Chem., 2016, 64, 1335-1343.
[26]
Fiat, A.M.; Miglilore-Samour, D.; Jolles, P.; Crouet, L.; Collier, C.; Caen, J. Biologically active peptides from milk proteins with emphasis on two example concerning antithrombotic and immuno-modulating activities. J. Dairy Sci., 1993, 76, 301-310.
[27]
Manso, M.A.; Escudero, C.; Alijo, M.; López-Fandino, R. Platelet aggregation inhibitory activity of bovine, ovine, and caprine kappa-casein macropeptides and their tryptic hydrolysates. J. Food Prot., 2002, 65, 1992-1996.
[28]
Rojas-Ronquillo, R.; Cruz-Guerrero, A.; Flores-Nájera, A.; Rodríguez-Serrano, G.; Gómez-Ruiz, L.; Reyes-Grajeda, J.P.; Jiménez-Guzmán, J.; García-Garibay, M. Antithrombotic and angiotensin-converting enzyme inhibitory properties of peptides released from bovine casein by Lactobacillus casei Shirota. Int. Dairy J., 2012, 26, 147-154.
[29]
Mikkelsen, T.L.; Rasmussen, E.; Olsen, A.; Barkholt, V.; Frøkiær, H. Immunogenicity of κ-casein and glycomacropeptide. J. Dairy Sci., 2006, 89, 824-830.
[30]
Otani, H.; Monnai, M. Inhibition of proliferative responses of mouse spleen lymphocytes by bovine milk κ-casein digests. Food Arg. Immunol., 1993, 5, 219-229.
[31]
Ortega-González, M.; Capitán-Canadas, F.; Requena, P.; Ocón, B.; Romero-Calvo, I.; Aranda, C.; Suárez, M.D.; Zarzuelo, A.; Sánchez de Medina, F.; Martinez-Augustin, O. Validation of bovine glycomacropeptide as an intestinal anti-inflammatory nutraceutical in the lymphocyte-transfer model of colitis. Br. J. Nutr., 2014, 111, 1202-1212.
[32]
Cheng, X.; Gao, D.; Chen, B.; Mao, X. Endotoxin-binding peptides derived from casein glycomacropeptide inhibit lipopolysaccharide-stimulated inflammatory responses via blockade of NF-κB activation in macrophages. Nutrients, 2015, 7, 3119-3137.
[33]
Inagaki, M.; Muranishi, H.; Yamada, K.; Kakehi, K.; Uchida, K.; Suzuki, T.; Yabe, T.; Nakagomi, T.; Nakagomi, O.; Kanamaru, Y. Bovine κ-casein inhibits human rotavirus (HRV) infection via direct binding of glycans to HRV. J. Dairy Sci., 2014, 97, 2653-2661.
[34]
Kawasaki, Y.; Isoda, H.; Tanimoto, M.; Dosako, S.; Idota, T.; Ahiko, K. Inhibition by lactoferrin and κ-casein glycomacropeptide of binding of cholera toxin to its receptor. Biosci. Biotechnol. Biochem., 1992, 56, 195-198.
[35]
Groves, M.L.; Kiddy, C.A. Polymorphism of γ-casein in cow’s milk. Arch. Biochem. Biophys., 1968, 126, 188-193.
[36]
Pihlanto, A.; Korhonen, H. In:TayloI, S.L.; Ed.; Bioactivepeptides and proteins. Adv. Food Nutr. Res., 2003, 47, 175-276.
[37]
Montiel, V.R.; Campuzano, S.; Torrente-Rodríguez, R.M.; Reviejo, A.J.; Pingarrón, J.M. Electrochemical magnetic beads-based immunosensing platform for the determination of a-lactalbumin in milk. Food Chem., 2016, 213, 595-601.
[38]
Kamau, S.M.; Cheison, S.C.; Chen, W.; Liu, X.M.; Lu, R.R. Alpha-lactalbumin: Its production technologies and bioactive peptides. Compr. Rev. Food Sci. F., 2010, 9, 197-212.
[39]
Indyk, H.E. Development and application of an optical biosensor immunoassay for α-lactalbumin in bovine milk. Int. Dairy J., 2009, 19, 36-42.
[40]
Crowley, S.V.; Dowling, A.P.; Caldeo, V.; Kelly, A.L.; O’Mahony, J.A. Impact of α-lactalbumin:β-lactoglobulin ratio on the heat stability of model infant milk formula protein systems. Food Chem., 2016, 194, 184-190.
[41]
Ruprichová, L.; Králová, M.; Borkovcová, I.; Vorlová, L.; Bedáňová, I. Determination of whey proteins in different types of milk. Acta Vet. Brno, 2014, 83, 67-72.
[42]
Noyelle, K.; Van Dael, H.J. Kinetics of conformational changes induced by the binding of various metal ions to bovine α-lactalbumin. J. Inorg. Biochem., 2002, 88, 69-76.
[43]
Fan, P.; Li, L.; Rezaei, A.; Eslamfam, S.; Che, D.; Ma, X. Metabolites of dietary protein and peptides by intestinal microbes and their impacts on gut. Curr. Protein Pept. Sci., 2015, 16, 646-654.
[44]
Fan, P.; Song, P.; Li, L.; Huang, C.; Chen, J.; Yang, W.; Qiao, S.; Wu, G.; Zhang, G.; Ma, X. Roles of biogenic amines in intestinal signaling. Curr. Protein Pept. Sci., 2017, 18, 532-540.
[45]
Indyk, H.E.; Hart, S.; Meerkerk, T.; Gill, B.D.; Woollard, D.C. The β-lactoglobulin content of bovine milk: Development and application of a biosensor immunoassay. Int. Dairy J., 2017, 73, 68-73.
[46]
Jameson, G.B.; Adams, J.J.; Creamer, L.K. Flexibility, functionality and hydrophobicity of bovine β-lactoglobulin. Int. Dairy J., 2002, 12(4), 319-329.
[47]
Levine, M.M. Vaccines and milk immunoglobulin concentrates for prevention of infectious diarrhea. J. Pediatr. Orthop., 1991, 118, 129-136.
[48]
Hao, L.Y.; Shan, Q.; Wei, J.Y.; Ma, F.T.; Sun, P. Lactoferrin: Major physiological functions and applications. Curr. Protein Pept. Sci., 2019, 20(2), 139-144.
[49]
Crichton, R.R. Proteins of iron storage and transport. Adv. Protein Chem., 1990, 40, 281-363.
[50]
Baker, E.N.; Baker, H.M. Molecular structure, binding properties and dynamics of lactoferrin. Cell. Mol. Life Sci., 2005, 62, 2531-2539.
[51]
Gifford, J.L.; Ishida, H.; Vogel, H.J. Structural characterization of the interaction of human lactoferrin with calmodulin. PLoS One, 2012, 7e51026
[52]
Wakabayashi, H.; Yamauchi, K.; Takase, M. Lactoferrin research, technology and applications. Int. Dairy J., 2006, 16, 1241-1251.
[53]
Neville, M.C. Lactoferrin secretion into milk: Comparison between bovine, murine and human milk. J. Anim. Sci., 2000, 78, 26-35.
[54]
Pierce, A.; Legrand, D.; Mazurier, J. Lactoferrin: A multifunctional protein. Med. Sci., 2009, 25, 361.
[55]
Giansanti, F.; Panella, G.; Leboffe, L.; Antonini, G. Lactoferrin from milk: Nutraceutical and pharmacological properties. Pharmaceuticals, 2016, 9, 61-76.
[56]
Kawakami, H.; Hiratsuka, M.; Dosako, S. Effects of iron-saturated lactoferrin on iron absorption. Agric. Biol. Chem., 1988, 52, 903-908.
[57]
Davidsson, L.; Kastenmayer, P.; Yuen, M.; Lönnerdal, B.; Hurrell, R.F. Influence of lactoferrin on iron absorption from human milk in infants. Pediatr. Res., 1994, 35, 117-124.
[58]
Conneely, O.M. Antiinflammatory activities of lactoferrin. J. Am. Coll. Nutr., 2001, 20, 389S-395S.
[59]
Taha, S.H.; Mehrez, M.A.; Sitohy, M.Z.; Dawood, A.G.I.A.; Hamid, A.E.; Kilany, W.H. Effectiveness of esterified whey proteins fractions against Egyptian Lethal Avian Influenza A (H5N1). Virol. J., 2010, 7, 330.
[60]
Tsuda, H.; Kozu, T.; Iinuma, G.; Ohashi, Y.; Saito, D.; Akasu, T.; Alexander, D.B.; Futakuchi, M.; Fukamachi, K.; Xu, J.; Kakizoe, T.; Iigo, M. Cancer prevention by bovine lactoferrin: From animal studies to human trial. Biometals, 2010, 23, 399-409.
[61]
Sanchez, L.; Calvo, M.; Brock, J.H. Biological role of lactoferrin. Arch. Dis. Child., 1992, 67, 657-661.
[62]
Valenti, P.; Antonini, G. Lactoferrin: An important host defence against microbial and viral attack. Cell. Mol. Life Sci., 2005, 62, 2576-2587.
[63]
Yen, C.C.; Shen, C.J.; Hsu, W.H.; Chang, Y.H.; Lin, H.T.; Chen, H.L.; Chen, C.M. Lactoferrin: An iron-binding antimicrobial protein against Escherichia coli infection. Biometals, 2011, 24, 585-594.
[64]
Rahman, M.M.; Kim, W.S.; Ito, T.; Kumura, H.; Shimazaki, K.I. Growth promotion and cell binding ability of bovine lactoferrin to Bifidobacterium longum. Anaerobe, 2009, 15, 133-137.
[65]
Redwan, E.M.; Uversky, V.N.; El-Fakharany, E.M.; Al-Mehdar, H. Potential lactoferrin activity against pathogenic viruses. C. R. Biol., 2014, 337, 581-595.
[66]
Park, Y.G.; Jeong, J.K.; Lee, J.H.; Lee, Y.J.; Seol, J.W.; Kim, S.J.; Hur, T.Y.; Jung, Y.H.; Kang, S.J.; Park, S.Y. Lactoferrin protects against prion protein-induced cell death in neuronal cells by preventing mitochondrial dysfunction. Int. J. Mol. Med., 2013, 31, 325-330.
[67]
Ogasawara, Y.; Imase, M.; Oda, H.; Wakabayashi, H.; Ishii, K. Lactoferrin directly scavenges hydroxyl radicals and undergoes oxidative self-degradation: A possible role in protection against oxidative DNA damage. Int. J. Mol. Sci., 2014, 15, 1003-1013.
[68]
Iigo, M.; Alexander, D.B.; Long, N.; Xu, J.; Fukamachi, K.; Futakuchi, M.; Takase, M.; Tsuda, H. Anticarcinogenesis pathways activated by bovine lactoferrin in the murine small intestine. Biochimie, 2009, 91, 86-101.
[69]
Xu, X.X.; Jiang, H.R.; Li, H.B.; Zhang, T.N.; Zhou, Q.; Liu, N. Apoptosis of stomach cancer cell SGC-7901 and regulation of Akt signaling way induced by bovine lactoferrin. J. Dairy Sci., 2010, 93, 2344-2350.
[70]
Duarte, D.C.; Nicolau, A.; Teixeira, J.A.; Rodrigues, L.R. The effect of bovine milk lactoferrin on human breast cancer cell lines. J. Dairy Sci., 2011, 94, 66-76.
[71]
Tsuda, H.; Sekine, K.; Fujita, K.; Ligo, M. Cancer prevention by bovine lactoferrin and underlying mechanisms - A review of experimental and clinical studies. Biochem. Cell Biol., 2002, 80, 131-136.
[72]
Kilara, A.; Panyam, D. Peptides from milk proteins and their properties. Crit. Rev. Food Sci. Nutr., 2003, 43, 607-633.
[73]
Neeser, J.R. Dental anti—plaque and anticaries agent. United States Patent 4992420 1991.
[74]
Beucher, S.; Levenez, F.; Yvon, M. Effect of caseino-maempeptide (CMP) on cholecystokinin(CCK) release in rat. Reprod. Nutr. Dev., 1994, 34, 613-614.
[75]
Liepke, C.; Zucht, H.D.; Forssmann, W.G.; Forssmann, W.G.; Ständker, L. Purification of novel peptide antibiotics from human milk. J. Chromatogr. B Biomed. Sci. Appl., 2001, 752, 369.
[76]
Playford, R.J.; Macdonald, C.E.; Johnson, W.S. Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. Am. J. Clin. Nutr., 2000, 72, 5.
[77]
Malkoski, M.; Dashper, S.G.; O’Briensimpson, N.M.; Talbo, G.H.; Macris, M.; Cross, K.J.; Reynolds, E.C. Kappacin, a novel antibacterial peptide from bovine milk. Antimicrob. Agents Chemother., 2001, 45, 2309-2315.
[78]
Dajanta, K.; Chukeatirote, E.; Apichartsrangkoon, A. Effect of lactoperoxidase system on keeping quality of raw cow’s milk in thailand. Int. J. Dairy Sci., 2008, 3, 112-116.
[79]
[74] Al-Baarri, A.N. Application of lactoperoxidase system using bovine whey and the effect of storage condition on lactoperoxidase activity. Int. J. Dairy Sci., 2011, 6, 72-78.
[80]
Gerson, C.; Sabater, J.; Scuri, M.; Torbati, A.; Coffey, R.; Abraham, J.W.; Lauredo, I.; Forteza, R.; Wanner, A.; Salathe, M.; Abraham, W.M.; Conner, G.E. The lactoperoxidase system functions in bacterial clearance of airways. Am. J. Resp. Cell Mol., 2000, 22, 665-671.
[81]
Almehdar, H.A.; El-Fakharany, E.M.; Uversky, V.N.; Redwan, E.M. Disorder in milk proteins: Structure, functional disorder, and biocidal potentials of lactoperoxidase. Curr. Protein Pept. Sci., 2015, 16, 352-365.
[82]
Boscolo, B.; Leal, S.S.; Ghibaudi, E.M.; Ghihaudi, E.M.; Gomes, C.M. Lactoperoxidase folding and catalysis relies on the stabilization of the alpha-helix rich core domain: a thermal unfolding study. Biochim. Biophys. Acta, 2007, 1774, 1164-1172.
[83]
Boscolo, B.; Leal, S.S.; Salgueiro, C.A.; Ghihaudi, E.M.; Gomes, C.M. The prominent conformational plasticity of lactoperoxidase: A chemical and pH stability analysis. BBA - Proteins Proteom., 2009, 1794, 1041-1048.


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VOLUME: 20
ISSUE: 7
Year: 2019
Page: [759 - 765]
Pages: 7
DOI: 10.2174/1389203720666190125104532
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