A large number of known proteins, often but not exclusively globular in structure, can bind small hydrophobic molecules. Some proteins serve a purpose of transporting these ligands either from one place to another or to cross barriers such as membranes. Dietary protein such as the milk proteins α-lactalbumin and β-lactoglobulin can bind vitamins, fatty acids (FA) or other small bioactive molecules. However, to date there is little knowledge on the biological implication of these host-ligands interaction. For instance, the structural similarity of β-lactoglobulin to other retinol or FA-binding proteins has given rise to much speculation of the role of this major milk protein, other than providing essential dietary amino acids. Therefore, the question arises whether complex formation of two major milk components has any impact on the structure/function relationship of protein or fatty acid.
By using the salts of the FA's and/or high pH, our group has produced complexes of α-lactalbumin and β-lactoglobulin with a number of different FA with medium to high binding affinities. Molar binding ratios (FA/protein) of up to 15 can be achieved. Tested FA’s are cytotoxic to tumour cells (U937, PC12, Caco2) by apoptosis. Binding FA to proteins can increase their cytotoxicity, which is strongly dependent on their binding affinity and stoichiometry, indicating the importance of the FA in the cell death. In this case, the protein is thought to facilitate the solubilisation of the FA and thereby increase local FA concentrations. However, complex formation can also decrease the cytotoxic due to a high water solubility of the FA as the case of linoleic acid. Therefore it appears that the solubility of FA at physiological pH is determining the amount of available FA, which governs the cytotoxicity.
Simulated infant in vitro gastric digestion of α-lactalbumin and oleic acid has demonstrated the potential complex formation. However, major questions regarding the relevance and/or presence of these weak complexes in complex food systems and potential implications for human health remain open to date.
Principle investigator: André Brodkorb andre.brodkorb@teagasc.ie
