Milk Lipoprotein Membranes and Their Imperative Enzymes

  • Nissim Silanikove
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 606)


There are two main sources of lipoprotein membranes in milk: the relatively well-defined milk fat globule membrane (MFGM) that covers the milk fat globules, and the much less attended lipoprotein source, in the form of vesicles floating in the milk serum. We challenge the common view that the milk serum lipoprotein membrane (MSLM) is secondly derived from the MFGM and present a different view suggesting that it represents Golgi-derived vesicles that are released intact to milk. The potential role of enzymes attached to the MSLMand MFGM is considered in detail for select ubiquitously expressed enzymes.


Mammary Gland Xanthine Oxidase Human Milk Bovine Milk Casein Micelle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Allen, K., & Cornforth, D. (2007). Antioxidant mechanism of milk mineral—High-affinity iron binding. Journal of Food Science, 72, C78–C83.CrossRefGoogle Scholar
  2. Babaei, H., Mansouri-Najand, L., Molaei, M. M., Kheradmand, A., & Sharifan, M. (2007). Assessment of lactate dehydrogenase, alkaline phosphatase and aspartate aminotransferase activities in cow's milk as an indicator of subclinical mastitis. Veterinary Research Communications, 31, 419–425.CrossRefGoogle Scholar
  3. Beumer, C., Wulferink, M., Raaben, W., Fiechter, D., Brands, R., & Seinen, W. (2003). Calf intestinal alkaline phosphatase, a novel therapeutic drug for lipopolysaccharide (LPS)-mediated diseases, attenuates LPS toxicity in mice and piglets. Journal of Pharmacology and Experimental Therapy, 307, 737–744.CrossRefGoogle Scholar
  4. Bingham, E. W., & Malin, E. L. (1992). Alkaline phosphatase in the lactating bovine mammary gland and the milk fat globule membrane. Release by phosphatidylinositol-specific phospholipase-C. Comparative Biochemistry and Physiology B—Biochemistry & Molcular Biology, 102, 213–218.CrossRefGoogle Scholar
  5. Bodrogi, L., Brands, R., Roaben, W., Seinen, W., Baranyi, M., Fiechter, D., & Bosze, Z. (2006). High level experssion of tissue-nonspecific alkaline phosphatase in the milk of transgenic rabbits. Transgenic Research, 15, 627–636.CrossRefGoogle Scholar
  6. Clare, D. A., & Swaisgood, H. E. (2000). Bioactive milk peptides: A prospectus. Journal of Dairy Science, 83, 1187–1195.Google Scholar
  7. Chikkappa, G. (1992). Control of neutrophils alkaline phosphatase synthesis by cytokines in health and disease. Experimental Haematology, 20, 388–390.Google Scholar
  8. Chuang, C. K., Lin, S. P., Lee, H. C., Wang, T. J., Shih, Y. S., Huang, T. Y., & Yeung, C. Y. (2005). Free amino acids in full-term and pre-term human milk and infant formula. Journal of Pediatric Gastroenterology and Nutrition, 40, 496–500.CrossRefGoogle Scholar
  9. Comhair, S. A. A., & Erzurum, S. C. (2005). The regulation and role of extracellular glutathione peroxidase. Antioxidant & Redox Signaling, 7, 72–79.CrossRefGoogle Scholar
  10. Dyer, K. D., & Rosenberg, H. F. (2006). The RNase a superfamily: Generation of diversity and innate host defense. Molecular Diversity, 10, 585–597.CrossRefGoogle Scholar
  11. Ekdahl, K. N., Ronquist, G., Nilsson, B., & Babiker, A. A. (2006). Possible immunoprotective and angiogenesis-promoting roles for malignant cell-derived prostasomes: A new paradigm for prostatic cancer? Current Topics in Complement Advances in Experimental Medicine and Biology, 586, 107–119.CrossRefGoogle Scholar
  12. Fishman, H. (1990). Alkaline phosphatase isozymes: Recent progress. Clinical Biochemistry, 23, 99–104.CrossRefGoogle Scholar
  13. Fox, P. F. (2003). Indigenous enzymes in milk. In P. F. Fox & P. L. H. McSweeney (Eds.), Advanced Dairy Chemistry, Vol. 1, Proteins (pp. 447–467). New York: Kluwer Academic/Plenum Publishers.Google Scholar
  14. Fox, P. F., & Kelly, A. L. (2006a). Indigenous enzymes in milk: Overview and historical aspects—Part 1. International Dairy Journal, 16, 500–516.CrossRefGoogle Scholar
  15. Fox, P. F., & Kelly, A. L. (2006b). Indigenous enzymes in milk: Overview and historical aspects—Part 2. International Dairy Journal, 16, 517–532.CrossRefGoogle Scholar
  16. Goding, J. W. (2000). Ecto-enzymes: Physiology meets pathology. Journal of Leukocyte Biology, 67, 285–311.Google Scholar
  17. Goldenberg, H. (1998). Molecular biology of plasma membrane redox enzymes: A survey of current knowledge. Protoplasma, 205, 3–9.CrossRefGoogle Scholar
  18. Harrison, R. (2006). Milk xanthine oxidase: Properties and physiological roles. International Dairy Journal, 16, 546–554.CrossRefGoogle Scholar
  19. Fujikake, N., & Ballatori, N. (2002). Glutatthione secretion into rat milk and its subsequent γ-glutamyltranspeptidase mediated catabolisim. Biology of the Neonate, 82, 134–138.CrossRefGoogle Scholar
  20. Heid, H. W., & Keenan, T. W. (2005). Intracellular origin and secretion of milk fat globules. European Journal of Cell Biology, 84, 245–258.CrossRefGoogle Scholar
  21. Huang, T. C., & Kuksis, A. (1967). A comparative study of lipids of globule membrane and fat core and of milk serum of cows. Lipids, 2, 453–460.CrossRefGoogle Scholar
  22. Kanno, C. (1990). Secretory membranes of the lactating mammary gland. Protoplasma, 159, 184–208.CrossRefGoogle Scholar
  23. Kennedy, E. J., Pillus, L., & Ghosh, G. (2005). Pho5p and newly identified nucleotide pyrophosphatases/phosphodiesterases regulate extracellular nucleotide phosphate metabolism in Saccharomyces cerevisiae. Eukaryotic Cell, 4, 1892–1901.CrossRefGoogle Scholar
  24. Kitchen, B. J. (1974). Comparison of properties of membranes isolated from bovine skim milk and cream. Biochimica et Biophysica Acta, 356, 257–269.CrossRefGoogle Scholar
  25. Low, H., & Crane, F. L. (1978). Redox function in plasma-membranes. Biochimica et Biophysica Acta, 515, 141–161.Google Scholar
  26. Makowski, G. S., & Ramsby, M. L. (2004). Differential effect of calcium phosphate and calcium pyrophosphate on binding of matrix metalloproteinases to fibrin: Comparison to a fibrin-binding protease from inflammatory joint fluids. Clinical and Experimental Immunology, 136, 176–187.CrossRefGoogle Scholar
  27. Manzano, M., Abadia-Molina, A. C., Olivares, E. G., Gil, A., & Rueda, R. (2003). Dietary nucleotides accelerate changes in intestinal lymphocyte maturation in weanling mice. Journal of Pediatric Gastroenterology and Nutrition, 37, 453–461.CrossRefGoogle Scholar
  28. Marcus, A. J., Broekman, M. J., Drosopoulos, J. H. F., Olson, K. E., Islam, N., Pinsky, D. J., & Levi, R. (2005). Role of CD39 (NTPDase-1) in thromboregulation, cerebroprotection, and cardioprotection. Seminars in Thrombosis and Hemostasis, 31, 234–246.CrossRefGoogle Scholar
  29. McGann, T. C., Buchheim, W., Kearney, R. D., & Richardson, T. (1983a). Composition and ultrastructure of calcium-phosphate citrate complexes in bovine-milk systems. Biochimica et Biophysica Acta, 760, 415–420.Google Scholar
  30. McGann, T. C., Kearney, R. D., & Buchheim, W. (1983b). Zinc phosphocitrate-casein complexes in bovine-milk systems. Kieler Milchwirtschaftliche Forschungsberichte, 35, 409–411.Google Scholar
  31. Michalczyk, A. A., Rieger, J., Allen, K. J., Mercer, J. F. B., & Ackland, M. L. (2000). Defective localization of the Wilson disease protein (ATP7B) in the mammary gland of the toxic milk mouse and the effects of copper supplementation. Biochemical Journal, 352, 565–571.CrossRefGoogle Scholar
  32. Morton, R. K. (1954). The lipoprotein particles in cow’s milk. Biochemical Journal, 57, 231–237.Google Scholar
  33. Paape, M. J., Bannerman, D. D., Zhao, X., & Lee J. W. (2003). The bovine neutrophil: Structure and function in blood and milk. Veterinary Research, 34, 597–627.CrossRefGoogle Scholar
  34. Patton, S., & Keenan, T. W. (1971). Relationship of milk phospholipids to membranes of secretory cell. Lipids, 6, 58–68.CrossRefGoogle Scholar
  35. Plantz, P. E., &. Patton, S. (1973). Plasma-membrane fragments in bovine and caprine skim milks. Biochimica et Biophysica Acta, 291, 51–60.CrossRefGoogle Scholar
  36. Plantz, P. E., Keenan, T. W., & Patton, S. (1973). Further evidence of plasma-membrane material in skim milk. Journal of Dairy Science, 56, 978–983.Google Scholar
  37. Poelstra, K., Bakker, W. W., Klok, P. A., Hardonk, M. J., & Meijer, D. K. (1997a). A physiologic function for alkaline phosphatase: Endotoxin detoxification. Laboratory Investigations, 76, 319–327.Google Scholar
  38. Poelstra, K., Bakker, W. W., Klok, P. A., Kamps, J. A., Hardonk, M. J., & Meijer, D. K. (1997b). Dephosphorylation of endotoxin by alkaline phosphatase in vivo. American Journal of Pathology, 151, 1163–1169.Google Scholar
  39. Robenek, H., Hofnagel, O., Buers, I., Lorkowski, S., Schnoor, M., Robenek, M. J., Heid, H., Troyer, D., & Severs, N. J. (2006a). Butyrophilin controls milk fat globule secretion. Proceedings of the National Academy of Sciences USA, 103, 10385–10390.Google Scholar
  40. Robenek, H., Hofnagel, O., Buers, I., Robenek, M. J., Troyer, D., & Severs, N. J. (2006b). Adipophilin-enriched domains in the ER membrane are sites of lipid droplet biogenesis. Journal of Cell Science, 119, 4215–4224.Google Scholar
  41. Roman, M., Sanchez, L., & Calvo, M. (1990). Changes in ribonuclease concentration during lactation in cow’s colostrum and milk. Netherlands Milk and Dairy Journal, 44, 207–212.Google Scholar
  42. Schallera, J. P., Bucka, R. H., & Ruedab, R. (2007). Ribonucleotides: Conditionally essential nutrients shown to enhance immune function and reduce diarrheal disease in infants. Seminars in Fetal and Neonatal Medicine, 12, 35–44.CrossRefGoogle Scholar
  43. Shahani, K. M., Harper, W. J., Jensen, R. G., Parry, R. M., & Zittle, C. A. (1973). Enzymes in bovine milk: A review. Journal of Dairy Science, 56, 531–543.CrossRefGoogle Scholar
  44. Shahani, K. M., Kwan, A. J., & Friend, B. A. (1980). Role and significance of enzymes in human milk. American Journal of Clinical Nutrition, 33, 1861–1868.Google Scholar
  45. Shennan, D. B. (1992). Is the milk-fat-globule membrane a model for mammary secretory-cell apical membrane? Experimental Physiology, 77, 653–656.Google Scholar
  46. Shirley, P. S., Bass, D. A., Lees, C. J., Parce, J. W., Waite, B. M., & Dechatelet, L. R. (1984). Co-localization of superoxide generation and NADP formation in plasma-membrane fractions from human-neutrophils. Inflammation, 8, 323–335.CrossRefGoogle Scholar
  47. Siegrist, C. A. (2001). Neonatal and early life vaccinology. Vaccine, 19, 3331–3346.CrossRefGoogle Scholar
  48. Silanikove, N., & Shapiro, F. (2007). Distribution of xanthine oxidase and xanthine dehydrogenase activity in bovine milk: Physiological and technological implications. International Dairy Journal, 17, 1188–1194.CrossRefGoogle Scholar
  49. Silanikove, N., Shamay, A., Shinder, D., & Moran, A. (2000). Stress down regulates milk yield in cows by plasmin induced beta-casein product that blocks K+ channels on the apical membranes. Life Sciences, 67, 2201–2212.CrossRefGoogle Scholar
  50. Silanikove, N., Shapiro, F., Shamay, A., & Leitner, G. (2005). Role of xanthine oxidase, lactoperoxidase, and NO in the innate immune system of mammary secretion during active involution in dairy cows: Manipulation with casein hydrolysates. Free Radical Biology Medicine, 38, 1139–1151.CrossRefGoogle Scholar
  51. Silanikove, N., Merin, U., & Leitner, G. (2006). Physiological role of indigenous milk enzymes: An overview of an evolving picture. International Dairy Journal, 16, 533–545.CrossRefGoogle Scholar
  52. Silva, F. V., Lopes, G. S., Nobrega, J. A., Souza, G. B., Rita, A., & Nogueria, A. (2001). Study on the protein-bound fraction of calcium, iron, magnesium and zinc in bovine milk. Spectrochimica Acta Part B, 56, 1909–1916.CrossRefGoogle Scholar
  53. Smith, E., Glegg, R. A., & Holt, C. (2004). Perspective on the structure and function of caseins and casein micelles. International Journal of Dairy Technology, 157, 121–126.CrossRefGoogle Scholar
  54. Takanaka, K., & Obrien, P. J. (1975). Mechanisms of H2O2 formation by leukocytes. 1. Evidence for a plasma-membrane location. Archives of Biochemistry and Biophysics, 169, 428–435.CrossRefGoogle Scholar
  55. Terkeltaub, R. A. (2001). Inorganic pyrophosphate generation and disposition in pathophysiology. American Journal of Physiology—Cell Physiology, 281, C1– C11.Google Scholar
  56. van Veen, S. Q., van Vliet, A. K., Wulferink, M., Brands, R., Boermeester, M. A., & van Gulik, T. M. (2005). Bovine intestinal alkaline phosphatase attenuates the inflammatory response in secondary peritonitis in mice. Infection and Immunity, 73, 4309– 4314.CrossRefGoogle Scholar
  57. Waninge, R., Kalda, E., Paulsson, M., Nylander, T., & Bergenståhl, B. (2004). Cryo-TEM of isolated milk fat globule membrane structures in cream. Physical Chemistry Chemical Physics, 6, 1518–1523.CrossRefGoogle Scholar
  58. Will, Y., Kaetzel, R. S., Brown, M. K., Fraley, T. S., & Reed, D. J. (2002). In vivo reversal of glutathione deficiency and susceptibility to in vivo dexamethasone-induced apoptosis by N-acetylcysteine and L-2-oxothiazolidine4-carboxylic acid, but not ascorbic acid, in thymocytes from γ-glutamyltranspeptidase-deficient knockout. Archives of Biochemistry and Biophysics, 397, 399–406.CrossRefGoogle Scholar
  59. Wooding, F. B. P. (1977). Comparative mammary fine structure. In M. Peaker (Ed.), Comparative Aspects of Lactation (pp. 1–41). New York: Academic Press.Google Scholar
  60. Xu, Q., Lu, Z., & Zhang, X. (2002). A novel role of alkaline phosphatase in protection from immunological liver injury in mice. Liver, 22, 8–14.CrossRefGoogle Scholar
  61. Ye, X. Y., & Ng, T. B. (2000). First demonstration of lactoribonuclease, a ribonuclease from bovine milk with similarity to bovine pancreatic ribonuclease. Life Sciences, 67, 2025–2032.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Nissim Silanikove
    • 1
  1. 1.Agricultural Research Organization, Institute of Animal ScienceIsrael

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