Apo-lactoferrin

Lactoferrin is the major whey protein present in breast milk (Teraguchi et ah, 1996) with many microbicidal properties (Leon-Sicairos et ah, 2006). The concentration of lactoferrin in milk has been reported as 1 g/liter in mature milk and 7 g/liter in colostrum (Houghton et ah, 1985). The concentration of lactoferrin in breast milk is controlled by the reproductive hormones prolactin and estrogen (Ward et ah, 2005). Lactoferrin has been demonstrated to resist digestion in the infant gut as it has been recovered intact from the stool of breast-fed infants (Bemt and Walker, 1999). Lactoferrin acts mainly in an iron-free state (apo-lactoferrin) and its microbicidal activity is reported to increase in proportion to its concentration in milk (Leon-Sicairos et ah, 2006). 

Leon-Sicairos, N., Lopez-Soto, F., Reyes-Lopez, M., Godinez-Vargas, D., Ordaz-Pichardo, C., and de la, G. M. (2006). Amoebicidal activity of milk, apo-lactoferrin, sIgA and lysozyme. Clin. Med. Res. 4,106-113. 

Bishop, J.G., Schanbacher, F.L., Ferguson, L.C., and Smith, L. 1976. In vitro growth inhibition of mastitis causing coliform bacteria by apo-lactoferrin and reversal of inhibition by citrate and high concentrations of apo-lactoferrin. Infect. Immun. 14, 911-918. 

Lactoferrin-mediated protection of mice from cytomegalovirus infection was reported to be linked with T-cell-dependent increase in natural killer cell activity (Shimizu et al, 1996). Lactoferrin potent antiviral inhibitory effect against HIV-1 in T-cell line was attributed to its action on HIV binding or on the entry of this virus into the cells no matter if it was in the apo or saturated form (Puddu et al, 1998). Antiviral and antitumor activities are correlated to... 

The first crystallographic studies on transferrins date back more than 20 years (58), and crystals of various transferrins have since been reported. These include the diferric forms of rabbit (59) and human (60) serum transferrins, hen (61) and duck (62) ovotransferrins, human (63) and bovine (64) lactoferrins, and the apo- (iron free) forms of human lactoferrin (65) and duck ovotransferrin (62). In spite of all this activity, the crystals in many cases have proved difficult to handle, and the X-ray analyses quite challenging. A low-resolution analysis of rabbit serum transferrin in 1979 demonstrated the bilobal nature of the molecule (66), but it was not until 1987, with the publication of the structure of human lactoferrin (67), that full details of a transferrin... 

Coordinates for human lactoferrin, in both diferric (78) and apo- (80) forms, for diferric rabbit serum transferrin (68), and for the three fragment structures, the proteolytic N-lobe of rabbit serum transferrin (74), the recombinant N-lobe of human lactoferrin (75) and the duck ovotransferrin quarter-molecule (76), all in their iron-bound forms, can be obtained from the Brookhaven Protein Data Bank (Brookhaven National Laboratory, Upton, New York). 

Transferrin is mainly synthesized in the hepatocytes. There are about 20 known variants. Iron is transported by transferrin (approx. 30% of transferrin is saturated with iron). With the help of a membrane receptor, the iron-transferrin complex is taken up and released in the liver cell, where it is immediately bound (because of its toxicity) to ferritin. The liver cells take up iron predominantly from transferrin, to a lesser degree also from haptoglobin, haemopexin, lactoferrin and circulating ferrin. Transferrin, which is mainly formed in the hepatocytes, may also bind and transport, in decreasing order, chromium, copper, manganese, cobalt, cadmium, zinc and nickel. The half-life of transferrin is 1 - 2 hours, which is very short in view of its total blood concentration of 3-4 mg. Approximately 0.4 g ferritin iron is stored in the liver. In the case of transferrin deficiency, its bacteriostatic and fungistatic effects are also reduced. Transferrin without iron saturation is known as apo-transferrin. (31, 66, 67)... 

The metabolism of lipid emulsions has long been considered to be similar to that of chylomicrons with intravascular lipolysis by lipoprotein lipase (LPL) being followed by tissue uptake of remnant particles. However, other studies have suggested that lipid emulsions are cleared from blood with less lipolysis than chylomicrons and that a substantial number of emulsions can be cleared as almost intact whole particles by different tissues. The metabolism of lipid emulsions is affected by many factors, including triglyceride (TG) composition. For example, MCT LCT emulsions are cleared faster from blood than pure LCT emulsions. Recently, it was reported that pure FO emulsion particles are removed from blood faster and by different pathways as compared with LCT emulsions. Removal of LCT emulsions is modulated by LPL, apolipoprotein E (apoE), LDL receptor (LDL-R), and lactoferrin-sensitive pathways. In contrast, clearance of FO emulsions relies on LPL to a much lesser extent and is apparently independent of apoE, LDL-R, and lactoferrin-sensitive pathways. It can therefore be noted that the materials selecteds to develop a nanoemulsion composition may not only affect the physicochemical properties and stability of the formulation but may alter significantly the biofate and efficacy of the nanoemulsions. 

P-Lactoglobulin Apo a-lactalbumin Lysozyme Lactoferrin aggregates (nnpnblished data)... 

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